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| Product NDC Code | 55135-132 | ||||
|---|---|---|---|---|---|
| Drug Name | Trodelvy |
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| Type | Brand | ||||
| Active Ingredients |
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| Route | INTRAVENOUS | ||||
| Dosage Form | POWDER, FOR SOLUTION | ||||
| Application Number | BLA761115 | ||||
| Labeler Name | Gilead Sciences | ||||
| Packages |
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| Check if available Online | Get Medication Prices online with Discount |
Overdosage of TRODELVY
Information about signs, symptoms, and laboratory findings of acute ovedosage and the general principles of overdose treatment.10 OVERDOSAGE In a clinical trial, planned doses of up to 18 mg/kg (approximately 1.8 times the maximum recommended dose of 10 mg/kg) of TRODELVY were administered. In these patients, a higher incidence of severe neutropenia was observed.
Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Neutropenia [see Warnings and Precautions (5.1) ] Diarrhea [see Warnings and Precautions (5.2) ] Hypersensitivity and Infusion-Related Reactions [see Warnings and Precautions (5.3) ] Nausea and Vomiting [see Warnings and Precautions (5.4) ] Most common adverse reactions (incidence ≥25%) are (including laboratory abnormalities) were decreased leukocyte count, decreased neutrophil count, decreased hemoglobin, diarrhea, nausea, decreased lymphocyte count, fatigue, alopecia, constipation, increased glucose, decreased albumin, vomiting, decreased appetite, decreased creatinine clearance, increased alkaline phosphatase, decreased magnesium, decreased potassium, and decreased sodium. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-888-983-4668 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The pooled safety population described in the Warnings and Precautions section reflect exposure to TRODELVY in 1063 patients from four studies, IMMU-132-01, ASCENT, TROPiCS-02, and TROPHY which included 366 patients with mTNBC, 322 patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, and 180 patients with mUC. TRODELVY was administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles at doses of 10 mg/kg until disease progression or unacceptable toxicity. Among the 1063 patients treated with TRODELVY, the median duration of treatment was 4.1 months (range: 0 to 63 months). In this pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%). Locally Advanced or Metastatic Triple-Negative Breast Cancer ASCENT Study The safety of TRODELVY was evaluated in a randomized, active-controlled, open-label study (ASCENT) in patients with mTNBC who had previously received a taxane and at least two prior chemotherapies. Patients were randomized (1:1) to receive either TRODELVY (n=258) or single agent chemotherapy (n=224) and were treated until disease progression or unacceptable toxicity [see Clinical Studies (14.1) ] . For patients treated with TRODELVY, the median duration of treatment was 4.4 months (range: 0 to 23 months). Serious adverse reactions occurred in 27% of patients receiving TRODELVY. Serious adverse reactions in > 1% of patients receiving TRODELVY included neutropenia (7%), diarrhea (4%), and pneumonia (3%). Fatal adverse reactions occurred in 1.2% of patients who received TRODELVY, including respiratory failure (0.8%) and pneumonia (0.4%). TRODELVY was permanently discontinued for adverse reactions in 5% of patients. Adverse reactions leading to permanent discontinuation in ≥ 1 % of patients who received TRODELVY were pneumonia (1%) and fatigue (1%). Adverse reactions leading to a treatment interruption of TRODELVY occurred in 63% of patients. The most frequent (≥5%) adverse reactions leading to a treatment interruption were neutropenia (47%), diarrhea (5%), respiratory infection (5%), and leukopenia (5%). Adverse reactions leading to a dose reduction of TRODELVY occurred in 22% of patients. The most frequent (>4%) adverse reactions leading to a dose reduction were neutropenia (11%) and diarrhea (5%). Granulocyte-colony stimulating factor (G-CSF) was used in 44% of patients who received TRODELVY. Tables 2 and 3 summarize adverse reactions and laboratory abnormalities, respectively, in the ASCENT study. Table 2: Adverse Reactions in ≥ 10% of Patients with mTNBC in ASCENT TRODELVY (n=258) Single Agent Chemotherapy (n=224) Adverse Reaction All Grades % Grade 3 – 4 % All Grades % Grade 3 – 4 % *Single agent chemotherapy included one of the following single-agents: eribulin (n=139), capecitabine (n=33), gemcitabine (n=38), or vinorelbine (except if patient had ≥ Grade 2 neuropathy, n=52). Graded per NCI CTCAE v.5.0. Gastrointestinal disorders Diarrhea 59 11 17 1 Nausea 57 3 26 0.4 Vomiting 33 2 16 1 Constipation 37 0.4 23 0 Abdominal Pain 30 3 12 1 Stomatitis Including stomatitis, glossitis, mouth ulceration, and mucosal inflammation 17 2 13 1 General disorders and administration site conditions Fatigue Including fatigue and asthenia 65 6 50 9 Pyrexia 15 0.4 14 2 Infections and infestation Urinary tract infection 13 0.4 8 0.4 Upper respiratory tract infection 12 0 3 0 Metabolism and nutrition disorders Decreased appetite 28 2 21 1 Musculoskeletal and connective tissue disorders Back pain 16 1 14 2 Arthralgia 12 0.4 7 0 Nervous system disorders Headache 18 0.8 13 0.4 Dizziness 10 0 7 0 Psychiatric disorders Insomnia 11 0 5 0 Respiratory, thoracic and mediastinal disorders Cough 24 0 18 0.4 Skin and subcutaneous tissue disorders Alopecia 47 0 16 0 Rash 12 0.4 5 0.4 Pruritus 10 0 3 0 Table 3: Laboratory Abnormalities in > 10% of Patients with mTNBC in ASCENT Laboratory Abnormality TRODELVY (n=258) Single Agent Chemotherapy (n=224) All Grades (%) Grade 3 – 4 (%) All Grades (%) Grade 3 – 4 (%) Hematology Decreased hemoglobin 94 9 57 6 Decreased lymphocyte count 88 31 40 24 Decreased leukocyte count 86 41 53 25 Decreased neutrophil count 78 49 48 36 Decreased platelet count 23 1.2 25 2.7 Chemistry Increased glucose 49 2.3 43 2.8 Decreased calcium 36 1.6 21 1.4 Decreased magnesium 33 0.4 20 0 Decreased potassium 33 4.3 28 0.9 Increased albumin 32 0.8 25 1.4 Increased aspartate aminotransferase 27 1.2 32 1.4 Increased alanine aminotransferase 26 1.2 26 1.8 Increased alkaline phosphatase 26 0 17 0.5 Decreased phosphate 26 7.8 20 3.3 Decreased sodium 22 0.4 17 0.5 Increased lactate dehydrogenase 18 0 22 0 Decreased glucose 10 0 3.2 0 Study IMMU-132-01 The safety of TRODELVY was evaluated in a single-arm, open-label study (IMMU-132-01) in patients with mTNBC and other malignancies, which included 108 patients with mTNBC who had received at least two prior anticancer therapies for metastatic disease [see Clinical Studies (14.1) ] . TRODELVY was administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles at doses up to 10 mg/kg until disease progression or unacceptable toxicity. The median treatment duration in these 108 patients was 5.1 months (range: 0 to 51 months). Serious adverse reactions occurred in 31% of the patients. Serious adverse reactions in > 1% of patients receiving TRODELVY included febrile neutropenia (6%) vomiting (5%), nausea (3%), dyspnea (3%), diarrhea (4%), anemia (2%), pleural effusion, neutropenia, pneumonia, dehydration (each 2%). TRODELVY was permanently discontinued for adverse reactions in 2% of patients. Adverse reactions leading to permanent discontinuation were anaphylaxis, anorexia/fatigue, headache (each 0.9%). Forty- five percent (45%) of patients experienced an adverse reaction leading to treatment interruption. The most common adverse reaction leading to treatment interruption was neutropenia (33%). Adverse reactions leading to dose reduction occurred in 33% of patients treated with TRODELVY, with 24% having one dose reduction, and 9% with two dose reductions. The most common adverse reaction leading to dose reductions was neutropenia/febrile neutropenia. Tables 4 and 5 summarize adverse reactions and laboratory abnormalities occurring in ≥10% of patients with mTNBC in the IMMU-132-01 study. Table 4: Adverse Reactions in ≥ 10% of Patients with mTNBC in IMMU-132-01 Adverse Reaction TRODELVY (n=108) Grade 1–4 (%) Grade 3–4 (%) Graded per NCI CTCAE v. 4.0 Any adverse reaction 100 71 Gastrointestinal disorders 95 21 Nausea 69 6 Diarrhea 63 9 Vomiting 49 6 Constipation 34 1 Abdominal pain Including abdominal pain, distention, pain (upper), discomfort, tenderness. 26 1 Mucositis Including stomatitis, esophagitis, and mucosal inflammation 14 1 General disorders and administration site conditions 77 9 Fatigue Including fatigue and asthenia. 57 8 Edema Including edema; and peripheral, localized, and periorbital edema 19 0 Pyrexia 14 0 Metabolism and nutrition disorders 68 22 Decreased appetite 30 1 Dehydration 13 5 Skin and subcutaneous tissue disorders 63 4 Alopecia 38 0 Rash Including rash; maculopapular, erythematous, generalized rash; dermatitis acneiform; skin disorder, irritation, and exfoliation 31 3 Pruritus 17 0 Dry Skin 15 0 Nervous system disorders 56 4 Headache 23 1 Dizziness 22 0 Neuropathy Including gait disturbance, hypoesthesia, muscular weakness, paresthesia, peripheral and sensory neuropathy 24 0 Dysgeusia 11 0 Infections and infestations 55 12 Urinary Tract Infection 21 3 Respiratory Infection Including lower and upper respiratory tract infection, pneumonia, influenza, viral upper respiratory infection, bronchitis and respiratory syncytial virus infection 26 3 Musculoskeletal and connective tissue disorders 54 1 Back pain 23 0 Arthralgia 17 0 Pain in extremity 11 0 Respiratory, thoracic and mediastinal disorders 54 5 Cough Includes cough and productive cough 22 0 Dyspnea Includes dyspnea and exertional dyspnea 21 3 Psychiatric disorders 26 1 Insomnia 13 0 Table 5: Laboratory Abnormalities observed in ≥ 10% of Patients while receiving TRODELVY in IMMU-132-01 Laboratory Abnormality TRODELVY (n=108) All Grades (%) Grade 3–4 (%) Hematology Decreased hemoglobin 93 6 Decreased leukocyte count 91 26 Decreased neutrophil count 82 32 Increased activated partial thromboplastin time 60 12 Decreased platelet count 30 3 Chemistry Increased alkaline phosphatase 57 2 Decreased magnesium 51 3 Decreased calcium 49 3 Increased aspartate aminotransferase 45 3 Decreased albumin 39 1 Increased alanine aminotransferase 35 2 Increased glucose 31 2.8 Decreased phosphate 29 5 Decrease magnesium 27 1.9 Decreased phosphate 27 6.5 Decreased sodium 25 4.7 Decreased potassium 24 3.7 Decreased glucose 19 2 Locally Advanced or Metastatic HR-Positive, HER2-Negative Breast Cancer TROPiCS-02 Study The safety of TRODELVY was evaluated in a randomized, active-controlled, open-label, study (TROPiCS-02) in patients with unresectable locally advanced or metastatic HR-positive, HER2-negative breast cancer whose disease has progressed after the following in any setting: a CDK 4/6 inhibitor, endocrine therapy, and a taxane; patients received at least two prior chemotherapies in the metastatic setting (one of which could be in the neoadjuvant or adjuvant setting if progression occurred within 12 months). Patients were randomized (1:1) to receive either TRODELVY (n=268) or single agent chemotherapy (n=249) and were treated until disease progression or unacceptable toxicity [see Clinical Studies (14.2) ] .For patients treated with TRODELVY, the median duration of treatment was 4.1 months (range: 0 to 63 months). Serious adverse reactions occurred in 28% of patients receiving TRODELVY. Serious adverse reactions in >1% of patients receiving TRODELVY included diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). Fatal adverse reactions occurred in 2% of patients who received TRODELVY including arrhythmia, COVID-19, nervous system disorder, pulmonary embolism, and septic shock (each 0.4%). TRODELVY was permanently discontinued for adverse reactions in 6% of patients. The most frequent (≥0.5%) adverse reactions leading to permanent discontinuation in patients who received TRODELVY were asthenia, general physical health deterioration, and neutropenia (each 0.7%). Adverse reactions leading to a treatment interruptions of TRODELVY occurred in 66% of patients. The most frequent (≥5%) adverse reaction leading to treatment interruption was neutropenia (50%). Adverse reaction leading to a dose reduction of TRODELVY occurred in 33% of patients. The most frequent (>5%) adverse reaction leading to dose reduction were neutropenia (16%) and diarrhea (8%). G-CSF was used in 54% of patients who received TRODELVY. Tables 6 and 7 summarize adverse reactions and laboratory abnormalities in the TROPiCS-02 study. Table 6: Adverse Reactions in ≥ 10% of Patients with HR+/HER2- mBC in TROPiCS-02 TRODELVY (n=268) Single Agent Chemotherapy (n=249) Adverse Reaction All Grades % Grade 3 – 4 % All Grades % Grade 3 – 4 % *Single agent chemotherapy included one of the following single-agents: eribulin (n=130), vinorelbine (n=63), gemcitabine (n=56), or capecitabine (n=22). Graded per NCI CTCAE v.5.0. Gastrointestinal disorders Diarrhea 62 10 23 1 Nausea 59 1 35 3 Constipation 34 1 25 0 Vomiting 23 1 16 2 Abdominal Pain 20 0 14 0 Dyspepsia Including dyspepsia, gastroesophageal reflux disease. 11 0 6 0 General disorders and administration site conditions Fatigue Including fatigue, asthenia. 60 8 51 4 Metabolism and nutrition disorders Decreased appetite 21 2 21 0 Hypokalemia 10 2 4 0 Musculoskeletal and connective tissue disorders Arthralgia 15 0 12 0 Nervous system disorders Headache 16 1 15 1 Respiratory, thoracic and mediastinal disorders Dyspnea Including dyspnea; exertional dyspnea 20 0 17 0 Cough 12 0 7 0 Skin and subcutaneous tissue disorders Alopecia 48 0 19 0 Pruritus 12 0 2 0 Other clinically significant adverse reactions in TROPiCS-02 (≤ 10%) include: hypotension (5%), pain (5%), rhinorrhea (5%), hypocalcemia (3%), nasal congestion (3%), skin hyperpigmentation, (3%), colitis or neutropenic colitis (2%), hyponatremia (2%), pneumonia (2%), proteinuria (1%), enteritis (0.4%). Table 7: Laboratory Abnormalities in > 10% of Patients with HR+/HER2- mBC in TROPiCS-02 Laboratory Abnormality TRODELVY (n=268) Single Agent Chemotherapy (n=249) All Grades (%) Grade 3 – 4 (%) All Grades (%) Grade 3 – 4 (%) Hematology Decreased leukocyte count 88 38 73 26 Decreased neutrophil count 83 53 67 40 Decreased hemoglobin 73 8 59 5 Decreased lymphocyte count 65 21 47 14 Decreased platelet count 21 1 30 4 Eosinophilia 13 0 4 0 Chemistry Increased glucose 37 0 31 0 Decreased albumin 32 0 27 0.4 Decreased creatinine clearance 24 2 19 1 Increased alkaline phosphatase 23 0 23 1 Decreased potassium 22 3 12 0.4 Increased alanine aminotransferase 21 1 31 2 Decreased sodium 19 1 17 0.4 Decreased magnesium 18 0 15 0 Decreased phosphate 17 0 10 0 Increased phosphate 16 0 16 0 Increased lactate dehydrogenase 16 0 28 0 Increased aspartate aminotransferase 15 2 25 1 Increased potassium 14 2 9 0 Locally Advanced or Metastatic Urothelial Cancer TROPHY Study The safety of TRODELVY was evaluated in a single-arm, open-label study in patients (n=113) with mUC who had received previous platinum-based and anti-PD-1/PD-L1 therapy. TRODELVY was administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles at doses of 10 mg/kg until disease progression or unacceptable toxicity. ( see Clinical Studies 14.3 ) Serious adverse reactions occurred in 44% of patients. Serious adverse reactions in >1% of patients receiving TRODELVY included infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), sepsis or bacteremia (5%), diarrhea (4%), anemia, venous thromboembolism, and small intestinal obstruction (3% each), pneumonia, abdominal pain, pyrexia, and thrombocytopenia (2% each). Fatal adverse reactions occurred in 3.6% of patients, including sepsis, respiratory failure, epistaxis, and completed suicide. TRODELVY was permanently discontinued for adverse reactions in 10% of patients. The most frequent adverse reaction leading to permanent discontinuation of study drug was neutropenia (4%, including febrile neutropenia in 2%). Adverse reactions leading to dose interruption occurred in 52% of patients. The most common adverse reactions leading to dose interruption were neutropenia (27%, including febrile neutropenia in 2%), infection (12%), and acute kidney injury (8%). Adverse reactions leading to a dose reduction of TRODELVY occurred in 42% of patients. The most common (> 4%) adverse reactions leading to a dose reduction were neutropenia (13%, including febrile neutropenia in 3%), diarrhea (11%), fatigue (8%), and infection (4%). Granulocyte-colony stimulating factor (G-CSF) was used in 47% of patients who received TRODELVY. The most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (78%), diarrhea (72%), decreased hemoglobin (71%), decreased lymphocyte count (71%), decreased neutrophil count (67%), nausea (66%), increased glucose (59%), fatigue (56%), decreased albumin (51%), alopecia (49%), decreased calcium (46%), decreased sodium (43%), decreased appetite (41%), decreased phosphate (41%), increased alkaline phosphatase (36%), constipation (34%), vomiting (34%), increased activated partial thromboplastin time (33%), increased creatinine (32%), decreased magnesium (31%), increased alanine aminotransferase (28%), increased lactate dehydrogenase (28%), abdominal pain (27%), decreased potassium (27%), increased aspartate aminotransferase (26%), and decreased platelet count (25%). Tables 8 and 9 summarize adverse reactions and laboratory abnormalities occurring in ≥10% of patients with mUC in the TROPHY study. Table 8: Adverse Reactions Reported in ≥ 15% (Grade 1–4) or ≥ 5% (Grade ≥ 3) of Patients Treated with TRODELVY in TROPHY Adverse Reaction TRODELVY n=113 Grade 1–4 % Grade 3–4 % Graded per NCI CTCAE v.5.0. Any adverse reaction 94 80 Gastrointestinal disorders Diarrhea 72 12 Nausea 66 4 Constipation 34 1 Vomiting 34 1 Abdominal pain Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, gastrointestinal pain 31 2 General disorders and administration site conditions Fatigue Includes fatigue and asthenia 68 5 Pyrexia 19 0 Edema Includes edema genital, edema peripheral, peripheral swelling 17 2 Skin and subcutaneous tissue disorders Alopecia 49 0 Rash Includes dermatitis acneiform, dermatitis bullous, erythema, lichen planus, photosensitivity reaction, pruritus, pruritus generalised, rash, rash macular, rash maculo-papular, rash pruritic, skin papilloma, skin toxicity 32 2 Metabolism and nutrition disorders Decreased appetite 41 3 Weight loss Includes failure to thrive and weight decreased 17 2 Renal and urinary disorders Acute kidney injury Includes acute kidney injury, blood creatinine increased, nephropathy toxic, renal failure, renal impairment 24 7 Hematuria 16 1 Infections and infestations Any infection Includes bacteremia, body tinea, bronchitis, candida infection, cellulitis, clostridium difficile infection, corona virus infection, device related infection, diverticulitis, escherichia bacteremia, escherichia pyelonephritis, folliculitis, gastroenteritis, gastroenteritis escherichia coli, herpes zoster, kidney infection, klebsiella sepsis, lung infection, nasopharyngitis, oral candidiasis, oral herpes, pneumonia, pyelonephritis, pyelonephritis acute, respiratory tract infection, rhinitis, sepsis, sinusitis, skin infection, tooth abscess, upper respiratory tract infection, urinary tract infection, urosepsis, vascular device infection, viral infection, viral pharyngitis, vulvovaginal mycotic infection 50 25 Urinary tract infection 19 12 Respiratory, thoracic and mediastinal disorders Cough Includes cough, productive cough, upper-airway cough syndrome 17 0 Dyspnea 16 0 Musculoskeletal disorders Back pain 16 0 Vascular disorders Venous thromboembolism Includes deep vein thrombosis, embolism, and pulmonary embolism 9 6 Other clinically significant adverse reactions in TROPHY (≤ 15%) include: peripheral neuropathy (12%), sepsis or bacteremia (9%), and pneumonia (4%). Table 9: Laboratory Abnormalities Reported in ≥ 20% (Any Grade) or ≥ 5% (Grade 3–4) of Patients Treated with TRODELVY in TROPHY Adverse Reaction TRODELVY n = 113 Any Grade Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available (range: 66 to 111 patients). % Grade 3–4 % Hematology Decreased leukocyte count 78 38 Decreased lymphocyte count 71 35 Decreased hemoglobin 71 18 Decreased neutrophil count 67 43 Decreased platelet count 25 2 Chemistry Increased glucose 59 8 Decreased albumin 51 4 Decreased calcium 46 9 Decreased sodium 43 1 Decreased phosphate 41 15 Increased alkaline phosphatase 36 0 Increased creatinine 32 5 Decreased magnesium 31 2 Increased alanine aminotransferase 28 2 Increased lactate dehydrogenase 28 0 Decreased potassium 27 0 Increased aspartate aminotransferase 26 2 Coagulation Increased activated partial thromboplastin time 33 6
| TRODELVY (n=258) | Single Agent Chemotherapy (n=224) | |||
|---|---|---|---|---|
| Adverse Reaction | All Grades % | Grade 3 – 4 % | All Grades % | Grade 3 – 4 % |
| *Single agent chemotherapy included one of the following single-agents: eribulin (n=139), capecitabine (n=33), gemcitabine (n=38), or vinorelbine (except if patient had ≥ Grade 2 neuropathy, n=52). | ||||
| Graded per NCI CTCAE v.5.0. | ||||
| Diarrhea | 59 | 11 | 17 | 1 |
| Nausea | 57 | 3 | 26 | 0.4 |
| Vomiting | 33 | 2 | 16 | 1 |
| Constipation | 37 | 0.4 | 23 | 0 |
| Abdominal Pain | 30 | 3 | 12 | 1 |
| Stomatitis | 17 | 2 | 13 | 1 |
| Fatigue | 65 | 6 | 50 | 9 |
| Pyrexia | 15 | 0.4 | 14 | 2 |
| Urinary tract infection | 13 | 0.4 | 8 | 0.4 |
| Upper respiratory tract infection | 12 | 0 | 3 | 0 |
| Decreased appetite | 28 | 2 | 21 | 1 |
| Back pain | 16 | 1 | 14 | 2 |
| Arthralgia | 12 | 0.4 | 7 | 0 |
| Headache | 18 | 0.8 | 13 | 0.4 |
| Dizziness | 10 | 0 | 7 | 0 |
| Insomnia | 11 | 0 | 5 | 0 |
| Cough | 24 | 0 | 18 | 0.4 |
| Alopecia | 47 | 0 | 16 | 0 |
| Rash | 12 | 0.4 | 5 | 0.4 |
| Pruritus | 10 | 0 | 3 | 0 |
| Laboratory Abnormality | TRODELVY (n=258) | Single Agent Chemotherapy (n=224) | ||
|---|---|---|---|---|
| All Grades (%) | Grade 3 – 4 (%) | All Grades (%) | Grade 3 – 4 (%) | |
| Decreased hemoglobin | 94 | 9 | 57 | 6 |
| Decreased lymphocyte count | 88 | 31 | 40 | 24 |
| Decreased leukocyte count | 86 | 41 | 53 | 25 |
| Decreased neutrophil count | 78 | 49 | 48 | 36 |
| Decreased platelet count | 23 | 1.2 | 25 | 2.7 |
| Increased glucose | 49 | 2.3 | 43 | 2.8 |
| Decreased calcium | 36 | 1.6 | 21 | 1.4 |
| Decreased magnesium | 33 | 0.4 | 20 | 0 |
| Decreased potassium | 33 | 4.3 | 28 | 0.9 |
| Increased albumin | 32 | 0.8 | 25 | 1.4 |
| Increased aspartate aminotransferase | 27 | 1.2 | 32 | 1.4 |
| Increased alanine aminotransferase | 26 | 1.2 | 26 | 1.8 |
| Increased alkaline phosphatase | 26 | 0 | 17 | 0.5 |
| Decreased phosphate | 26 | 7.8 | 20 | 3.3 |
| Decreased sodium | 22 | 0.4 | 17 | 0.5 |
| Increased lactate dehydrogenase | 18 | 0 | 22 | 0 |
| Decreased glucose | 10 | 0 | 3.2 | 0 |
| Adverse Reaction | TRODELVY (n=108) | |
|---|---|---|
| Grade 1–4 (%) | Grade 3–4 (%) | |
| Graded per NCI CTCAE v. 4.0 | ||
| 100 | 71 | |
| 95 | 21 | |
| Nausea | 69 | 6 |
| Diarrhea | 63 | 9 |
| Vomiting | 49 | 6 |
| Constipation | 34 | 1 |
| Abdominal pain | 26 | 1 |
| Mucositis | 14 | 1 |
| 77 | 9 | |
| Fatigue | 57 | 8 |
| Edema | 19 | 0 |
| Pyrexia | 14 | 0 |
| 68 | 22 | |
| Decreased appetite | 30 | 1 |
| Dehydration | 13 | 5 |
| 63 | 4 | |
| Alopecia | 38 | 0 |
| Rash | 31 | 3 |
| Pruritus | 17 | 0 |
| Dry Skin | 15 | 0 |
| 56 | 4 | |
| Headache | 23 | 1 |
| Dizziness | 22 | 0 |
| Neuropathy | 24 | 0 |
| Dysgeusia | 11 | 0 |
| 55 | 12 | |
| Urinary Tract Infection | 21 | 3 |
| Respiratory Infection | 26 | 3 |
| 54 | 1 | |
| Back pain | 23 | 0 |
| Arthralgia | 17 | 0 |
| Pain in extremity | 11 | 0 |
| 54 | 5 | |
| Cough | 22 | 0 |
| Dyspnea | 21 | 3 |
| 26 | 1 | |
| Insomnia | 13 | 0 |
| Laboratory Abnormality | TRODELVY (n=108) | |
|---|---|---|
| All Grades (%) | Grade 3–4 (%) | |
| Decreased hemoglobin | 93 | 6 |
| Decreased leukocyte count | 91 | 26 |
| Decreased neutrophil count | 82 | 32 |
| Increased activated partial thromboplastin time | 60 | 12 |
| Decreased platelet count | 30 | 3 |
| Increased alkaline phosphatase | 57 | 2 |
| Decreased magnesium | 51 | 3 |
| Decreased calcium | 49 | 3 |
| Increased aspartate aminotransferase | 45 | 3 |
| Decreased albumin | 39 | 1 |
| Increased alanine aminotransferase | 35 | 2 |
| Increased glucose | 31 | 2.8 |
| Decreased phosphate | 29 | 5 |
| Decrease magnesium | 27 | 1.9 |
| Decreased phosphate | 27 | 6.5 |
| Decreased sodium | 25 | 4.7 |
| Decreased potassium | 24 | 3.7 |
| Decreased glucose | 19 | 2 |
| TRODELVY (n=268) | Single Agent Chemotherapy (n=249) | |||
|---|---|---|---|---|
| Adverse Reaction | All Grades % | Grade 3 – 4 % | All Grades % | Grade 3 – 4 % |
| *Single agent chemotherapy included one of the following single-agents: eribulin (n=130), vinorelbine (n=63), gemcitabine (n=56), or capecitabine (n=22). | ||||
| Graded per NCI CTCAE v.5.0. | ||||
| Diarrhea | 62 | 10 | 23 | 1 |
| Nausea | 59 | 1 | 35 | 3 |
| Constipation | 34 | 1 | 25 | 0 |
| Vomiting | 23 | 1 | 16 | 2 |
| Abdominal Pain | 20 | 0 | 14 | 0 |
| Dyspepsia | 11 | 0 | 6 | 0 |
| Fatigue | 60 | 8 | 51 | 4 |
| Decreased appetite | 21 | 2 | 21 | 0 |
| Hypokalemia | 10 | 2 | 4 | 0 |
| Arthralgia | 15 | 0 | 12 | 0 |
| Headache | 16 | 1 | 15 | 1 |
| Dyspnea | 20 | 0 | 17 | 0 |
| Cough | 12 | 0 | 7 | 0 |
| Alopecia | 48 | 0 | 19 | 0 |
| Pruritus | 12 | 0 | 2 | 0 |
| Laboratory Abnormality | TRODELVY (n=268) | Single Agent Chemotherapy (n=249) | ||
|---|---|---|---|---|
| All Grades (%) | Grade 3 – 4 (%) | All Grades (%) | Grade 3 – 4 (%) | |
| Decreased leukocyte count | 88 | 38 | 73 | 26 |
| Decreased neutrophil count | 83 | 53 | 67 | 40 |
| Decreased hemoglobin | 73 | 8 | 59 | 5 |
| Decreased lymphocyte count | 65 | 21 | 47 | 14 |
| Decreased platelet count | 21 | 1 | 30 | 4 |
| Eosinophilia | 13 | 0 | 4 | 0 |
| Increased glucose | 37 | 0 | 31 | 0 |
| Decreased albumin | 32 | 0 | 27 | 0.4 |
| Decreased creatinine clearance | 24 | 2 | 19 | 1 |
| Increased alkaline phosphatase | 23 | 0 | 23 | 1 |
| Decreased potassium | 22 | 3 | 12 | 0.4 |
| Increased alanine aminotransferase | 21 | 1 | 31 | 2 |
| Decreased sodium | 19 | 1 | 17 | 0.4 |
| Decreased magnesium | 18 | 0 | 15 | 0 |
| Decreased phosphate | 17 | 0 | 10 | 0 |
| Increased phosphate | 16 | 0 | 16 | 0 |
| Increased lactate dehydrogenase | 16 | 0 | 28 | 0 |
| Increased aspartate aminotransferase | 15 | 2 | 25 | 1 |
| Increased potassium | 14 | 2 | 9 | 0 |
| Adverse Reaction | TRODELVY n=113 | |
|---|---|---|
| Grade 1–4 % | Grade 3–4 % | |
| Graded per NCI CTCAE v.5.0. | ||
| 94 | 80 | |
| Diarrhea | 72 | 12 |
| Nausea | 66 | 4 |
| Constipation | 34 | 1 |
| Vomiting | 34 | 1 |
| Abdominal pain | 31 | 2 |
| Fatigue | 68 | 5 |
| Pyrexia | 19 | 0 |
| Edema | 17 | 2 |
| Alopecia | 49 | 0 |
| Rash | 32 | 2 |
| Decreased appetite | 41 | 3 |
| Weight loss | 17 | 2 |
| Acute kidney injury | 24 | 7 |
| Hematuria | 16 | 1 |
| Any infection | 50 | 25 |
| Urinary tract infection | 19 | 12 |
| Cough | 17 | 0 |
| Dyspnea | 16 | 0 |
| Back pain | 16 | 0 |
| Venous thromboembolism | 9 | 6 |
| Adverse Reaction | TRODELVY n = 113 | |
|---|---|---|
| Any Grade | Grade 3–4 | |
| Decreased leukocyte count | 78 | 38 |
| Decreased lymphocyte count | 71 | 35 |
| Decreased hemoglobin | 71 | 18 |
| Decreased neutrophil count | 67 | 43 |
| Decreased platelet count | 25 | 2 |
| Increased glucose | 59 | 8 |
| Decreased albumin | 51 | 4 |
| Decreased calcium | 46 | 9 |
| Decreased sodium | 43 | 1 |
| Decreased phosphate | 41 | 15 |
| Increased alkaline phosphatase | 36 | 0 |
| Increased creatinine | 32 | 5 |
| Decreased magnesium | 31 | 2 |
| Increased alanine aminotransferase | 28 | 2 |
| Increased lactate dehydrogenase | 28 | 0 |
| Decreased potassium | 27 | 0 |
| Increased aspartate aminotransferase | 26 | 2 |
| Increased activated partial thromboplastin time | 33 | 6 |
TRODELVY Drug Interactions
Information about and practical guidance on preventing clinically significant drug/drug and drug/food interactions that may occur in people taking the drug.7 DRUG INTERACTIONS UGT1A1 inhibitors or inducers: Avoid concomitant use. ( 7 ) 7.1 Effect of Other Drugs on TRODELVY UGT1A1 Inhibitors Concomitant administration of TRODELVY with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38 [see Warning and Precaution (5.5) and Clinical Pharmacology (12.3 , 12.5) ] . Avoid administering UGT1A1 inhibitors with TRODELVY. UGT1A1 Inducers Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers [see Warning and Precaution (5.5) and Clinical Pharmacology (12.3 , 12.5) ] . Avoid administering UGT1A1 inducers with TRODELVY.
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Sacituzumab govitecan-hziy is a Trop-2-directed antibody-drug conjugate. Sacituzumab is a humanized antibody that recognizes Trop-2. The small molecule, SN-38, is a topoisomerase I inhibitor, which is covalently attached to the antibody by a linker. Pharmacology data suggest that sacituzumab govitecan-hziy binds to Trop-2-expressing cancer cells and is internalized with the subsequent release of SN-38 via hydrolysis of the linker. SN-38 interacts with topoisomerase I and prevents re-ligation of topoisomerase I-induced single strand breaks. The resulting DNA damage leads to apoptosis and cell death. Sacituzumab govitecan-hziy decreased tumor growth in mouse xenograft models of triple-negative breast cancer. 12.2 Pharmacodynamics The TRODELVY exposure-response relationships and pharmacodynamic time course for efficacy have not been fully characterized. Cardiac electrophysiology The maximum mean change from baseline was 9.7 msec (the upper bound of the two-sided 90% confidence interval is 16.8 msec) at the recommended dose. A positive exposure-response relationship was observed between QTc increases and SN-38 concentrations. 12.3 Pharmacokinetics The serum pharmacokinetics of sacituzumab govitecan-hziy and SN-38 were evaluated in patients with mBC who received sacituzumab govitecan-hziy as a single agent at a dose of 10 mg/kg. The pharmacokinetic parameters of sacituzumab govitecan-hziy and free SN-38 are presented in Table 10. Table 10: Summary of Mean PK Parameters (CV%) of Sacituzumab Govitecan-hziy and Free SN-38 Parameters estimated based on population PK analyses Sacituzumab govitecan-hziy (N=693) Free SN-38 (N=681) C max : maximum serum concentration from 0–168 hours after the first dose AUC 0–168 : area under serum concentration curve through 168 hours after the first dose C max [ng/mL] 239000 (11%) 98.0 (45%) AUC 0–168 [ng*h/mL] 5640000 (22%) 3696 (56%) Distribution Based on population pharmacokinetic analysis, steady state volume of distribution of sacituzumab govetican-hziy is 3.6L. Elimination The median elimination half-life (t 1/2 ) of sacituzumab govitecan-hziy and free SN-38 in patients with metastatic triple negative breast cancer was 23.4 and 17.6 hours, respectively. Based on population pharmacokinetic analysis, the estimated mean (%CV) clearance of the sacituzumab govitecan-hziy is 0.13 L/h (12%). Metabolism No metabolism studies with sacituzumab govitecan-hziy have been conducted. SN-38 (the small molecule moiety of sacituzumab govitecan-hziy) is metabolized via UGT1A1. The glucuronide metabolite of SN-38 (SN-38G) was detectable in the serum of patients. Specific Populations Pharmacokinetic analyses in patients treated with TRODELVY did not identify an effect of age (27 to 88 years), race (White, Black, or Asian), or mild renal impairment to moderate renal impairment (CLcr 30 to 89 mL/min) on the pharmacokinetics of sacituzumab govitecan-hziy. Renal elimination is known to contribute minimally to the excretion of SN-38, the small molecule moiety of sacituzumab govitecan-hziy. There are no data on the pharmacokinetics of sacituzumab govitecan-hziy in patients with severe renal impairment (CLcr 15 to 29 mL/min), or end-stage renal disease (CLcr < 15 mL/min). Patients with Hepatic Impairment The exposure of sacituzumab govitecan-hziy is similar in patients with mild hepatic impairment (total bilirubin ≤ ULN with AST > ULN, or bilirubin >1.0 to ≤ 1.5 ULN with any AST; n=257) to patients with normal hepatic function (total bilirubin or AST < ULN; n=526). Sacituzumab govitecan-hziy and free SN-38 exposures are unknown in patients with moderate (total bilirubin > 1.5 to 3.0 × ULN) or severe (total bilirubin > 3.0 × ULN) hepatic impairment. Drug Interaction Studies No drug-drug interaction studies were conducted with sacituzumab govitecan-hziy or its components. Inhibitors or inducers of UGT1A1 may increase or decrease SN-38 exposure, respectively [see Drug Interactions (7) ] . 12.5 Pharmacogenomics SN-38 is metabolized via UGT1A1 [ see Clinical Pharmacology (12.3) ]. Genetic variants of the UGT1A1 gene such as the UGT1A1*28 allele lead to reduced UGT1A1 enzyme activity. Individuals who are homozygous or heterozygous for the UGT1A1*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia from TRODELVY compared to individuals who are wildtype (*1/*1) [see Warnings and Precautions (5.5) ]. Approximately 20% of the Black or African American population, 10% of the White population, and 2% of the East Asian population are homozygous for the UGT1A1*28 allele (*28/*28). Approximately 40% of the Black or African American population, 50% of the White population, and 25% of the East Asian population are heterozygous for the UGT1A1*28 allele (*1/*28). Decreased function alleles other than UGT1A1*28 may be present in certain populations. 12.6 Immunogenicity The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of TRODELVY. During the median 4-month treatment period across clinical studies in patients treated with TRODELVY, 9 (1.1%) of 785 patients developed antibodies to sacituzumab govitecan; 6 of these patients (0.8% of all patients treated with TRODELVY) had neutralizing antibodies against sacituzumab govitecan. Because of the low occurrence of anti-drug antibodies, the effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of sacituzumab govitecan is unknown.
| Sacituzumab govitecan-hziy (N=693) | Free SN-38 (N=681) | |
|---|---|---|
| Cmax: maximum serum concentration from 0–168 hours after the first dose | ||
| AUC0–168: area under serum concentration curve through 168 hours after the first dose | ||
| 239000 (11%) | 98.0 (45%) | |
| 5640000 (22%) | 3696 (56%) | |
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.12.1 Mechanism of Action Sacituzumab govitecan-hziy is a Trop-2-directed antibody-drug conjugate. Sacituzumab is a humanized antibody that recognizes Trop-2. The small molecule, SN-38, is a topoisomerase I inhibitor, which is covalently attached to the antibody by a linker. Pharmacology data suggest that sacituzumab govitecan-hziy binds to Trop-2-expressing cancer cells and is internalized with the subsequent release of SN-38 via hydrolysis of the linker. SN-38 interacts with topoisomerase I and prevents re-ligation of topoisomerase I-induced single strand breaks. The resulting DNA damage leads to apoptosis and cell death. Sacituzumab govitecan-hziy decreased tumor growth in mouse xenograft models of triple-negative breast cancer.
Pharmacodynamics
Information about any biochemical or physiologic pharmacologic effects of the drug or active metabolites related to the drugÕs clinical effect in preventing, diagnosing, mitigating, curing, or treating disease, or those related to adverse effects or toxicity.12.2 Pharmacodynamics The TRODELVY exposure-response relationships and pharmacodynamic time course for efficacy have not been fully characterized. Cardiac electrophysiology The maximum mean change from baseline was 9.7 msec (the upper bound of the two-sided 90% confidence interval is 16.8 msec) at the recommended dose. A positive exposure-response relationship was observed between QTc increases and SN-38 concentrations.
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.12.3 Pharmacokinetics The serum pharmacokinetics of sacituzumab govitecan-hziy and SN-38 were evaluated in patients with mBC who received sacituzumab govitecan-hziy as a single agent at a dose of 10 mg/kg. The pharmacokinetic parameters of sacituzumab govitecan-hziy and free SN-38 are presented in Table 10. Table 10: Summary of Mean PK Parameters (CV%) of Sacituzumab Govitecan-hziy and Free SN-38 Parameters estimated based on population PK analyses Sacituzumab govitecan-hziy (N=693) Free SN-38 (N=681) C max : maximum serum concentration from 0–168 hours after the first dose AUC 0–168 : area under serum concentration curve through 168 hours after the first dose C max [ng/mL] 239000 (11%) 98.0 (45%) AUC 0–168 [ng*h/mL] 5640000 (22%) 3696 (56%) Distribution Based on population pharmacokinetic analysis, steady state volume of distribution of sacituzumab govetican-hziy is 3.6L. Elimination The median elimination half-life (t 1/2 ) of sacituzumab govitecan-hziy and free SN-38 in patients with metastatic triple negative breast cancer was 23.4 and 17.6 hours, respectively. Based on population pharmacokinetic analysis, the estimated mean (%CV) clearance of the sacituzumab govitecan-hziy is 0.13 L/h (12%). Metabolism No metabolism studies with sacituzumab govitecan-hziy have been conducted. SN-38 (the small molecule moiety of sacituzumab govitecan-hziy) is metabolized via UGT1A1. The glucuronide metabolite of SN-38 (SN-38G) was detectable in the serum of patients. Specific Populations Pharmacokinetic analyses in patients treated with TRODELVY did not identify an effect of age (27 to 88 years), race (White, Black, or Asian), or mild renal impairment to moderate renal impairment (CLcr 30 to 89 mL/min) on the pharmacokinetics of sacituzumab govitecan-hziy. Renal elimination is known to contribute minimally to the excretion of SN-38, the small molecule moiety of sacituzumab govitecan-hziy. There are no data on the pharmacokinetics of sacituzumab govitecan-hziy in patients with severe renal impairment (CLcr 15 to 29 mL/min), or end-stage renal disease (CLcr < 15 mL/min). Patients with Hepatic Impairment The exposure of sacituzumab govitecan-hziy is similar in patients with mild hepatic impairment (total bilirubin ≤ ULN with AST > ULN, or bilirubin >1.0 to ≤ 1.5 ULN with any AST; n=257) to patients with normal hepatic function (total bilirubin or AST < ULN; n=526). Sacituzumab govitecan-hziy and free SN-38 exposures are unknown in patients with moderate (total bilirubin > 1.5 to 3.0 × ULN) or severe (total bilirubin > 3.0 × ULN) hepatic impairment. Drug Interaction Studies No drug-drug interaction studies were conducted with sacituzumab govitecan-hziy or its components. Inhibitors or inducers of UGT1A1 may increase or decrease SN-38 exposure, respectively [see Drug Interactions (7) ] .
| Sacituzumab govitecan-hziy (N=693) | Free SN-38 (N=681) | |
|---|---|---|
| Cmax: maximum serum concentration from 0–168 hours after the first dose | ||
| AUC0–168: area under serum concentration curve through 168 hours after the first dose | ||
| 239000 (11%) | 98.0 (45%) | |
| 5640000 (22%) | 3696 (56%) | |
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.4 CONTRAINDICATIONS TRODELVY is contraindicated in patients who have experienced a severe hypersensitivity reaction to TRODELVY [see Warnings and Precautions (5.3) ] . Severe hypersensitivity reaction to TRODELVY. ( 4 , 5.3 )
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.11 DESCRIPTION Sacituzumab govitecan-hziy is a Trop-2 directed antibody and topoisomerase inhibitor conjugate, composed of the following three components: the humanized monoclonal antibody, hRS7 IgG1κ (also called sacituzumab), which binds to Trop-2 (the trophoblast cell-surface antigen-2); the drug SN-38, a topoisomerase inhibitor; a hydrolysable linker (called CL2A), which links the humanized monoclonal antibody to SN-38. The recombinant monoclonal antibody is produced by mammalian (murine myeloma) cells, while the small molecule components SN-38 and CL2A are produced by chemical synthesis. Sacituzumab govitecan-hziy contains on average 7 to 8 molecules of SN-38 per antibody molecule. Sacituzumab govitecan-hziy has a molecular weight of approximately 160 kilodaltons. Sacituzumab govitecan-hziy has the following chemical structure. TRODELVY (sacituzumab govitecan-hziy) for injection is a sterile, preservative-free, off-white to yellowish lyophilized powder for intravenous use in a 50 mL clear glass single-dose vial, with a rubber stopper and crimp-sealed with an aluminum flip-off cap. Each single-dose vial of TRODELVY delivers 180 mg sacituzumab govitecan-hziy, 71.7 mg 2-(N-morpholino) ethane sulfonic acid (MES), 1.8 mg polysorbate 80 and 153.99 mg trehalose. Reconstitution with 20 mL of 0.9% Sodium Chloride Injection, USP, results in a concentration of 10 mg/mL with a pH of 6.5. Chemical Structure
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.2 DOSAGE AND ADMINISTRATION Do NOT substitute TRODELVY for or use with other drugs containing irinotecan or its active metabolite SN-38. ( 2.1 ) For intravenous infusion only. Do not administer as an intravenous push or bolus. The recommended dose is 10 mg/kg once weekly on Days 1 and 8 of continuous 21-day treatment cycles until disease progression or unacceptable toxicity. ( 2.2 ) Premedication for prevention of infusion reactions and prevention of chemotherapy-induced nausea and vomiting is recommended. ( 2.2 ) Monitor patients during the infusion and for at least 30 minutes after completion of infusion. Treatment interruption and/or dose reduction may be needed to manage adverse reactions. ( 2.2 ) See Full Prescribing Information for preparation and administration instructions. ( 2.4 ) 2.1 Important Use Information Do NOT substitute TRODELVY for or use with other drugs containing irinotecan or its active metabolite SN-38. 2.2 Recommended Dosage The recommended dosage of TRODELVY is 10 mg/kg administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles. Continue treatment until disease progression or unacceptable toxicity. Do not administer TRODELVY at doses greater than 10 mg/kg. Administer TRODELVY as an intravenous infusion only. Do not administer as an intravenous push or bolus. First infusion: Administer infusion over 3 hours. Observe patients during the infusion and for at least 30 minutes following the initial dose, for signs or symptoms of infusion-related reactions [see Warning and Precautions (5.3) ] . Subsequent infusions: Administer infusion over 1 to 2 hours if prior infusions were tolerated. Observe patients during the infusion and for at least 30 minutes after infusion. Premedication Prior to each dose of TRODELVY, premedication for prevention of infusion reactions and prevention of chemotherapy-induced nausea and vomiting (CINV) is recommended. Premedicate with antipyretics, H1 and H2 blockers prior to infusion, and corticosteroids may be used for patients who had prior infusion reactions. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK 1 receptor antagonist, as well as other drugs as indicated). 2.3 Dose Modifications for Adverse Reactions Infusion-related Reactions Slow or interrupt the infusion rate of TRODELVY if the patient develops an infusion-related reaction. Permanently discontinue TRODELVY for life-threatening infusion-related reactions [see Warnings and Precautions (5.3) ] Dose Modifications for Adverse Reactions Withhold or discontinue TRODELVY to manage adverse reactions as described in Table 1. Do not re-escalate the TRODELVY dose after a dose reduction for adverse reactions has been made. Table 1: Dose Modifications for Adverse Reactions Adverse Reaction Occurrence Dose Modification Severe Neutropenia [see Warnings and Precautions (5.1) ] Grade 4 neutropenia ≥ 7 days OR Grade 3–4 febrile neutropenia, OR At time of scheduled treatment, Grade 3–4 neutropenia which delays dosing by 2 or 3 weeks for recovery to ≤ Grade 1 First 25% dose reduction and administer granulocyte-colony stimulating factor (G-CSF). Second 50% dose reduction and administer G-CSF. Third Discontinue treatment and administer G-CSF. At time of scheduled treatment, Grade 3–4 neutropenia which delays dosing beyond 3 weeks for recovery to ≤ Grade 1 First Discontinue treatment and administer G-CSF. Severe Non-Neutropenic Toxicity Grade 4 non-hematologic toxicity of any duration, OR Any Grade 3–4 nausea, vomiting or diarrhea due to treatment that is not controlled with antiemetics and anti-diarrheal agents [see Warnings and Precautions (5.2 , 5.4) ] , OR Other Grade 3–4 non-hematologic toxicity persisting > 48 hours despite optimal medical management, OR At time of scheduled treatment, Grade 3–4 non-neutropenic hematologic or non-hematologic toxicity, which delays dose by 2 or 3 weeks for recovery to ≤ Grade 1 First 25% dose reduction Second 50% dose reduction Third Discontinue treatment In the event of Grade 3–4 non-neutropenic hematologic or non-hematologic toxicity, which does not recover to ≤ Grade 1 within 3 weeks First Discontinue treatment 2.4 Preparation and Administration Reconstitution TRODELVY is a hazardous drug. Follow applicable special handling and disposal procedures 1 . Calculate the required dose (mg) of TRODELVY based on the patient's body weight at the beginning of each treatment cycle (or more frequently if the patient's body weight changed by more than 10% since the previous administration) [see Dosage and Administration (2.2) ] . Allow the required number of vials to warm to room temperature. Using a sterile syringe, slowly inject 20 mL of 0.9% Sodium Chloride Injection, USP, into each 180 mg TRODELVY vial. Each vial contains overfill to compensate for liquid loss during preparation and after reconstitution, the total resulting volume delivers a concentration of 10 mg/mL . Gently swirl vials and allow to dissolve for up to 15 minutes. Do not shake. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be free of visible particulates, clear and yellow. Do not use the reconstituted solution if it is cloudy or discolored. Use immediately to prepare a diluted TRODELVY infusion solution. Dilution Calculate the required amount of the reconstituted TRODELVY solution needed to obtain the appropriate dose according to the patient's body weight. Determine the final volume of the infusion solution to deliver the appropriate dose at a TRODELVY concentration range of 1.1 mg/mL to 3.4 mg/mL. Use 0.9% Sodium Chloride Injection, USP only since the stability of the reconstituted TRODELVY solution has not been determined with other infusion-based solutions. Use a polyvinyl chloride, polypropylene/polyethylene, polyolefin, or ethylene vinyl acetate infusion bag. Withdraw and discard the volume of 0.9% Sodium Chloride Injection, USP from the final infusion bag that is necessary to achieve the indicated TRODELVY concentration following the addition of the calculated amount of reconstituted TRODELVY solution. Withdraw the calculated amount of the reconstituted TRODELVY solution from the vial(s) using a syringe. Discard any unused portion remaining in the vial(s). To minimize foaming, slowly inject the calculated amount of reconstituted TRODELVY solution into the infusion bag. Do not shake the contents. If not used immediately, the infusion bag containing TRODELVY solution can be stored refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours protected from light. After refrigeration, administer diluted solution at room temperature up to 25°C (77°F) within 8 hours (including infusion time). Do Not Freeze or Shake. Administration Administer TRODELVY as an intravenous infusion. Protect infusion bag from light. The infusion bag should be covered during administration to the patient until dosing is complete. It is not necessary to cover the infusion tubing or to use light-protective tubing during the infusion. An infusion pump may be used. Do not mix TRODELVY, or administer as an infusion, with other medicinal products. Upon completion of the infusion, flush the intravenous line with 20 mL 0.9% Sodium Chloride Injection, USP.
| Adverse Reaction | Occurrence | Dose Modification |
|---|---|---|
| First | 25% dose reduction and administer granulocyte-colony stimulating factor (G-CSF). | |
| Second | 50% dose reduction and administer G-CSF. | |
| Third | Discontinue treatment and administer G-CSF. | |
| First | Discontinue treatment and administer G-CSF. | |
| Grade 4 non-hematologic toxicity of any duration, OR Any Grade 3–4 nausea, vomiting or diarrhea due to treatment that is not controlled with antiemetics and anti-diarrheal agents | First | 25% dose reduction |
| Second | 50% dose reduction | |
| Third | Discontinue treatment | |
| In the event of Grade 3–4 non-neutropenic hematologic or non-hematologic toxicity, which does not recover to ≤ Grade 1 within 3 weeks | First | Discontinue treatment |
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.3 DOSAGE FORMS AND STRENGTHS For injection: 180 mg off-white to yellowish lyophilized powder in a single-dose vial. For injection: 180 mg lyophilized powder in single-dose vials for reconstitution. ( 3 )
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1 INDICATIONS AND USAGE TRODELVY is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Locally Advanced or Metastatic Breast Cancer Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. ( 1.1 , 14.1 ) Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. ( 1.1 , 14.2 ) Locally Advanced or Metastatic Urothelial Cancer Locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. a ( 1.2 ) a This indication is approved under accelerated approval based on tumor response rate and duration of response [see Clinical Studies (14.3) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. 1.1 Locally Advanced or Metastatic Breast Cancer TRODELVY is indicated for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. TRODELVY is indicated for the treatment of adult patients with unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. 1.2 Locally Advanced or Metastatic Urothelial Cancer TRODELVY is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication is approved under accelerated approval based on tumor response rate and duration of response [see Clinical Studies (14.3) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Spl product data elements
Usually a list of ingredients in a drug product.TRODELVY SACITUZUMAB GOVITECAN SACITUZUMAB GOVITECAN SACITUZUMAB GOVITECAN 2-(N-morpholino)ethanesulfonic acid trehalose polysorbate 80
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been conducted with sacituzumab govitecan-hziy. SN-38 was clastogenic in an in vitro mammalian cell micronucleus test in Chinese hamster ovary cells and was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay. Fertility studies with sacituzumab govitecan-hziy have not been conducted. In a repeat-dose toxicity study in cynomolgus monkeys, intravenous administration of sacituzumab govitecan-hziy on Day 1 and Day 4 resulted in endometrial atrophy, uterine hemorrhage, increased follicular atresia of the ovary, and atrophy of vaginal epithelial cells at doses ≥ 60 mg/kg (≥ 6 times the human recommended dose of 10 mg/kg based on body weight).
Nonclinical toxicology
Information about toxicology in non-human subjects.13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been conducted with sacituzumab govitecan-hziy. SN-38 was clastogenic in an in vitro mammalian cell micronucleus test in Chinese hamster ovary cells and was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay. Fertility studies with sacituzumab govitecan-hziy have not been conducted. In a repeat-dose toxicity study in cynomolgus monkeys, intravenous administration of sacituzumab govitecan-hziy on Day 1 and Day 4 resulted in endometrial atrophy, uterine hemorrhage, increased follicular atresia of the ovary, and atrophy of vaginal epithelial cells at doses ≥ 60 mg/kg (≥ 6 times the human recommended dose of 10 mg/kg based on body weight).
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.PRINCIPAL DISPLAY PANEL - 180 mg Vial Label NDC 55135-132-01 Rx only TRODELVY ® sacituzumab govitecan-hziy For injection 180 mg per vial For intravenous infusion only Warning: Hazardous Drug Single-dose vial Discard unused portion XXXXXXXX PRINCIPAL DISPLAY PANEL - 180 mg Vial Label
PRINCIPAL DISPLAY PANEL - 180 mg Vial Box NDC 55135-132-01 Rx only TRODELVY ® sacituzumab govitecan-hziy For injection 180 mg per vial For intravenous infusion only Warning: Hazardous Drug Reconstitute and dilute immediately prior to use Single-dose vial Discard unused portion 1 Vial GILEAD PRINCIPAL DISPLAY PANEL - 180 mg Vial Box
Recent major changes
A list of the section(s) that contain substantive changes that have been approved by FDA in the product labeling. The headings and subheadings, if appropriate, affected by the change are listed together with each section’s identifying number and the month and year on which the change was incorporated in the labeling.Boxed Warning 02/2023 Indications and Usage ( 1.1 ) 02/2023 Dosage and Administration ( 2.3 ) 02/2023 Dosage and Administration ( 2.4 ) 12/2022 Warnings and Precautions ( 5.1 , 5.2 , 5.3 , 5.4 , 5.5 ) 02/2023
| 02/2023 | |
| Indications and Usage ( | 02/2023 |
| Dosage and Administration ( | 02/2023 |
| Dosage and Administration ( | 12/2022 |
| Warnings and Precautions ( | 02/2023 |
Spl unclassified section
Information not classified as belonging to one of the other fields. Approximately 40% of labeling with effective_time between June 2009 and August 2014 have information in this field.Manufactured by: Gilead Sciences, Inc. 333 Lakeside Dr. Foster City, CA 94404, USA U.S. License No. 2258
TRODELVY: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information) Neutropenia Advise patients of the risk of neutropenia. Instruct patients to immediately contact their healthcare provider if they experience fever, chills, or other signs of infection [see Warnings and Precautions (5.1) ] . Diarrhea Advise patients of the risk of diarrhea. Instruct patients to immediately contact their healthcare provider if they experience diarrhea for the first time during treatment; black or bloody stools; symptoms of dehydration such as lightheadedness, dizziness, or faintness; inability to take fluids by mouth due to nausea or vomiting; or inability to get diarrhea under control within 24 hours [see Warnings and Precautions (5.2) ]. Hypersensitivity and Infusion-Related Reactions Inform patients of the risk of serious infusion reactions and anaphylaxis. Instruct patients to immediately contact their healthcare provider if they experience facial, lip, tongue, or throat swelling, urticaria, difficulty breathing, lightheadedness, dizziness, chills, rigors, wheezing, pruritus, flushing, rash, hypotension, or fever that occur during or within 24 hours following the infusion [see Warnings and Precautions (5.3) ] . Nausea/Vomiting Advise patients of the risk of nausea and vomiting. Premedication according to established guidelines with a two or three drug regimen for prevention of chemotherapy-induced nausea and vomiting (CINV) is also recommended. Additional antiemetics, sedatives, and other supportive measures may also be employed as clinically indicated. All patients should receive take-home medications for preventing and treating delayed nausea and vomiting, with clear instructions. Instruct patients to immediately contact their healthcare provider if they experience uncontrolled nausea or vomiting [see Warnings and Precautions (5.4) ] . Embryo-Fetal Toxicity Advise female patients to contact their healthcare provider if they are pregnant or become pregnant. Inform female patients of the risk to a fetus and potential loss of the pregnancy [see Use in Specific Populations (8.1) ]. Contraception Advise female patients of reproductive potential to use effective contraception during treatment and for 6 months after the last dose of TRODELVY [see Use in Specific Populations (8.3) ] . Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of TRODELVY [see Use in Specific Populations (8.3) ] . Lactation Advise women not to breastfeed during treatment and for 1 month after the last dose of TRODELVY [see Use in Specific Populations (8.2) ]. Infertility Advise females of reproductive potential that TRODELVY may impair fertility [see Use in Specific Populations (8.3) ].
Spl patient package insert
Information necessary for patients to use the drug safely and effectively.The Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 04/2024 Patient Information TRODELVY ® (troh-DELL-vee) (sacituzumab govitecan-hziy) for injection, for intravenous use What is the most important information I should know about TRODELVY? TRODELVY can cause serious side effects, including: Low white blood cell count (neutropenia). Low white blood cell counts are common with TRODELVY and can sometimes be severe and lead to infections that can be life-threatening or cause death. Your healthcare provider should check your blood cell counts during treatment with TRODELVY. If your white blood cell count is too low, your healthcare provider may need to lower your dose of TRODELVY, give you a medicine to help prevent low blood cell count with future doses of TRODELVY, or in some cases may stop TRODELVY. Your healthcare provider may need to give you antibiotic medicines if you develop fever while your white blood cell count is low. Call your healthcare provider right away if you develop any of the following signs of infection during treatment with TRODELVY : fever chills cough shortness of breath burning or pain when you urinate Severe diarrhea. Diarrhea is common with TRODELVY and can also be severe. Severe diarrhea can lead to loss of too much body fluid (dehydration) and kidney problems. Your healthcare provider should monitor you for diarrhea and give you medicine as needed to help control your diarrhea. If you lose too much body fluid, your healthcare provider may need to give you fluids and electrolytes to replace body salts. If you develop diarrhea during treatment with TRODELVY, your healthcare provider should check to see if diarrhea may be caused by an infection. Your healthcare provider may decrease your dose or stop TRODELVY if your diarrhea is severe and cannot be controlled with anti-diarrheal medicines. Call your healthcare provider right away: the first time that you get diarrhea during treatment with TRODELVY if you have black or bloody stools if you have symptoms of losing too much body fluid and body salts, such as lightheadedness, dizziness or faintness if you are unable to take fluids by mouth due to nausea or vomiting if you are not able to get your diarrhea under control within 24 hours What is TRODELVY? TRODELVY is a prescription medicine used to treat adults with: a type of breast cancer called triple-negative breast cancer (TNBC), which is estrogen and progesterone hormone receptor (HR)-negative and human epidermal growth factor receptor 2 (HER2)-negative. TRODELVY may be used: when your breast cancer has spread to other parts of the body (metastatic) or cannot be removed by surgery, and if you previously received two or more prior treatments, including at least one treatment for metastatic disease. a type of breast cancer that is HR-positive and HER2-negative. TRODELVY may be used: when your breast cancer has spread to other parts of the body or cannot be removed by surgery, and if you previously received endocrine therapy and at least two additional treatments for metastatic disease. bladder cancer and cancers of the urinary tract that have spread or cannot be removed by surgery. TRODELVY may be used if you have: received a platinum-containing chemotherapy medicine and also received an immunotherapy medicine. It is not known if TRODELVY is safe and effective in people with moderate or severe liver problems. It is not known if TRODELVY is safe and effective in children. Do not receive TRODELVY if you have had a severe allergic reaction to TRODELVY. Ask your healthcare provider if you are not sure. Before receiving TRODELVY, tell your healthcare provider about all of your medical conditions, including if you: have been told that you carry a gene for uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28. People who carry this gene have an increased risk of getting side effects with TRODELVY, especially low white blood cell counts, a fever while your white blood cell count is low, and low red blood cell counts. See " What is the most important information I should know about TRODELVY? " have liver problems. are pregnant or plan to become pregnant. TRODELVY can harm your unborn baby. Your healthcare provider should check to see if you are pregnant before you start receiving TRODELVY. Females who can become pregnant should use effective birth control during treatment and for 6 months after your last dose of TRODELVY. Talk to your healthcare provider about birth control choices that may be right for you during this time. Tell your healthcare provider right away if you become pregnant during treatment with TRODELVY. Males with a female partner who can become pregnant should use effective birth control during treatment and for 3 months after your last dose of TRODELVY. are breastfeeding or plan to breastfeed. It is not known if TRODELVY passes into your breastmilk and can harm your baby. Do not breastfeed during treatment and for 1 month after your last dose of TRODELVY. Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. Certain medicines may affect the way TRODELVY works. How will I receive TRODELVY? Your healthcare provider will give you TRODELVY into your vein through an intravenous (IV) line. TRODELVY is given 1 time each week, on Day 1 and on Day 8 of a 21-day treatment cycle. You will receive the first dose of TRODELVY over 3 hours. If you tolerate the first dose well, future doses may be given over 1 to 2 hours. Before each dose of TRODELVY, you will receive medicines to help prevent infusion-related reactions, and nausea and vomiting. You will be monitored for side effects during and for at least 30 minutes after you receive each infusion of TRODELVY. Your healthcare provider may slow down or temporarily stop your infusion of TRODELVY if you have an infusion-related reaction, or permanently stop TRODELVY if you have a life-threatening infusion-related reaction. Your healthcare provider will decide how long you will continue to receive TRODELVY. What are the possible side effects of TRODELVY? TRODELVY can cause serious side effects, including: See " What is the most important information I should know about TRODELVY? " Allergic and infusion-related reactions . Serious allergic reactions can happen during treatment with TRODELVY, including life-threatening allergic reactions, and infusion-related reactions. Tell your healthcare provider or nurse right away if you get any of the following symptoms of an allergic or infusion-related reaction during your infusion of TRODELVY or within 24 hours after you receive a dose of TRODELVY: swelling of your face, lips, tongue, or throat hives skin rash, itching, or flushing of your skin fever difficulty breathing or wheezing lightheadedness, dizziness, feeling faint or pass out chills or shaking chills (rigors) Nausea and vomiting . Nausea and vomiting are common with TRODELVY and can sometimes be severe. Before each dose of TRODELVY, you will receive medicines to help prevent nausea and vomiting. You should be given medicines to take home with you, along with instructions about how to take them to help prevent and treat any nausea and vomiting after you receive TRODELVY. Call your healthcare provider right away if you have nausea or vomiting that is not controlled with the medicines prescribed for you. Your healthcare provider may decide to decrease your dose or stop TRODELVY if your nausea and vomiting is severe and cannot be controlled with anti-nausea medicines. The most common side effects of TRODELVY include: decreased white blood cell (leukocyte and lymphocyte) and red blood cell counts feeling tired or weak hair loss constipation increased sugar levels in the blood decreased protein levels (albumin) in the blood decreased appetite changes in kidney function test increased levels of enzyme called alkaline phosphatase in the blood (test for liver or bone problems) decreased levels of magnesium, potassium, and sodium in the blood TRODELVY may cause fertility problems in females, which could affect your ability to have a baby. Talk to your healthcare provider if fertility is a concern for you. These are not all of the possible side effects of TRODELVY. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. General information about the safe and effective use of TRODELVY. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about TRODELVY that is written for health professionals. What are the ingredients in TRODELVY? Active ingredient : sacituzumab govitecan-hziy Inactive ingredients : 2-(N-morpholino) ethane sulfonic acid (MES), polysorbate 80 and trehalose Manufactured by: Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA 94404, USA U.S. License No. 2258 761115-GS-008 For more information about TRODELVY, go to www.TRODELVY.com or call 1-888-983-4668.
| The Patient Information has been approved by the U.S. Food and Drug Administration. | Revised: 04/2024 | |
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| TRODELVY may cause fertility problems in females, which could affect your ability to have a baby. Talk to your healthcare provider if fertility is a concern for you. These are not all of the possible side effects of TRODELVY. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. | ||
Clinical studies
This field may contain references to clinical studies in place of detailed discussion in other sections of the labeling.14 CLINICAL STUDIES 14.1 Locally Advanced or Metastatic Triple-Negative Breast Cancer ASCENT Efficacy was evaluated in a multicenter, open-label, randomized study (ASCENT; NCT02574455) conducted in 529 patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who had relapsed after at least two prior chemotherapies for breast cancer (one of which could be in the neoadjuvant or adjuvant setting provided progression occurred within a 12 month period). All patients received previous taxane treatment in either the adjuvant, neoadjuvant, or advanced stage unless there was a contraindication or intolerance to taxanes during or at the end of the first taxane cycle. Magnetic resonance imaging (MRI) to determine brain metastases was required prior to enrollment for patients with known or suspected brain metastases. Patients with brain metastases were allowed to enroll up to a pre-defined maximum of 15% of patients in the ASCENT study. Patients with known Gilbert's disease or bone-only disease were excluded. Patients were randomized (1:1) to receive TRODELVY 10 mg/kg as an intravenous infusion on Days 1 and 8 of a 21-day (n=267) or physician's choice of single agent chemotherapy (n=262). Single agent chemotherapy was determined by the investigator before randomization from one of the following choices: eribulin (n=139), capecitabine (n=33), gemcitabine (n=38), or vinorelbine (n=52). Patients were treated until disease progression or unacceptable toxicity. The major efficacy outcome was progression-free survival (PFS) in patients without brain metastases at baseline (i.e., BMNeg) as measured by a blinded, independent, centralized review assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Additional efficacy measures included PFS for the full population (all patients with and without brain metastases) and overall survival (OS). The median age of patients in the full population (n = 529) was 54 years (range: 27 to 82 years); 99.6% were female; 79% were White, 12% were Black/African American; and 81% of patients were < 65 years of age. All patients had an ECOG performance status of 0 (43%) or 1 (57%). Forty-two percent of patients had hepatic metastases, 9% were BRCA1/BRCA2 mutational status positive, and 70% were TNBC at diagnosis. Twelve percent had baseline brain metastases previously treated and stable (n=61; 32 on TRODELVY arm and 29 on single agent chemotherapy arm). Overall, 29% of patients had received prior PD-1/PD-L1 therapy. Thirteen percent of patients in the TRODELVY group in the full population received only 1 prior line of systemic therapy in the metastatic setting. The efficacy results are summarized in Table 11 and are shown in Figure 1 and Figure 2. Efficacy results for the subgroup of patients who had received only 1 prior line of systemic therapy in the metastatic setting (in addition to having disease recurrence or progression within 12 months of neoadjuvant/adjuvant systemic therapy) were consistent with those who had received at least two prior lines in the metastatic setting. Table 11: Efficacy Results from ASCENT All Randomized Patients TRODELVY n=267 Single Agent Chemotherapy n=262 CI = Confidence Interval Progression-Free Survival PFS is defined as the time from the date of randomization to the date of the first radiological disease progression or death due to any cause, whichever comes first. per BICR Disease Progression or Death (%) 190 (71%) 171 (65%) Median PFS in months (95% CI) 4.8 (4.1, 5.8) 1.7 (1.5, 2.5) Hazard ratio Stratified log-rank test adjusted for stratification factors: number of prior chemotherapies, presence of known brain metastases at study entry, and region. (95% CI) 0.43 (0.35, 0.54) p-value <0.0001 Overall Survival Deaths (%) 179 (67%) 206 (79%) Median OS in months (95% CI) 11.8 (10.5, 13.8) 6.9 (5.9, 7.6) Hazard ratio (95% CI) 0.51 (0.41, 0.62) p-value <0.0001 Figure 1: Kaplan-Meier Plot of PFS by BICR (All Randomized Patients) in ASCENT Figure 2: Kaplan-Meier Plot of OS (All Randomized Patients) in ASCENT An exploratory analysis of PFS in patients with previously treated, stable brain metastases showed a stratified HR of 0.65 (95% CI: 0.35, 1.22). The median PFS in the TRODELVY arm was 2.8 months (95% CI: 1.5, 3.9) and the median PFS with single agent chemotherapy was 1.6 months (95% CI: 1.3, 2.9). Exploratory OS analysis in the same population showed a stratified HR of 0.87 (95% CI: 0.47, 1.63). The median OS in the TRODELVY arm was 6.8 months (95% CI: 4.7, 14.1) and the median OS with single agent chemotherapy was 7.4 months (95% CI: 4.7, 11.1). Figure 1 Figure 2 IMMU-132-01 The efficacy of TRODELVY was evaluated in a multicenter, single-arm, study (NCT01631552) that enrolled 108 patients with metastatic triple-negative breast cancer (mTNBC) who had received at least two prior anticancer therapies for metastatic disease. Patients with bulky disease, defined as a mass >7 cm, were not eligible. Patients with treated brain metastases not receiving high dose steroids (> 20 mg prednisone or equivalent) for at least four weeks were eligible. Patients with known Gilbert's disease were excluded. Patients received TRODELVY 10 mg/kg intravenously on Days 1 and 8 of a 21-day treatment cycle. Patients were treated with TRODELVY until disease progression or intolerance to the therapy. Tumor imaging was obtained every 8 weeks, with confirmatory CT/MRI scans obtained 4–6 weeks after an initial partial or complete response, until progression requiring treatment discontinuation. Major efficacy outcome measures were investigator assessed overall response rate (ORR) using RECIST 1.1 and duration of response. The median age was 55 years (range: 31 to 80 years); 87% of patients were younger than 65 years. The majority of patients were female (99%) and White (76%). At study entry, all patients had an ECOG performance status of 0 (29%) or 1 (71%). Seventy-six percent had visceral disease, 42% had hepatic metastases, 56% had lung/pleura metastases, and 2% had brain metastases. Twelve patients (11%) had Stage IV disease at the time of initial diagnosis. The median number of prior systemic therapies received in the metastatic setting was 3 (range: 2 to 10). Prior chemotherapies in the metastatic setting included carboplatin or cisplatin (69%), gemcitabine (55%), paclitaxel or docetaxel (53%), capecitabine (51%), eribulin (45%), doxorubicin (24%), vinorelbine (16%), cyclophosphamide (19%), and ixabepilone (8%). Overall, 98% of patients had received prior taxanes and 86% had received prior anthracyclines either in the (neo)adjuvant or metastatic setting. Table 12 summarizes the efficacy results. Table 12: Efficacy results for patients with mTNBC in IMMU-132-01 TRODELVY (N=108) CI: confidence interval +: denotes ongoing Overall Response Rate investigator assessment ORR (95% CI) 33.3% (24.6, 43.1) Complete response 2.8% Partial response 30.6% Response duration Number of responders 36 Median, Months (95% CI) 7.7 (4.9, 10.8) Range, Months 1.9+, 30.4+ % with duration ≥6 months 55.6% % with duration ≥12 months 16.7% 14.2 Locally Advanced or Metastatic HR-Positive, HER2-Negative Breast Cancer TROPiCS-02 Study The efficacy of TRODELVY was evaluated in a multicenter, open label, randomized study (TROPiCS-02; NCT03901339) conducted in 543 patients with unresectable locally advanced or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer whose disease has progressed after the following in any setting: a CDK 4/6 inhibitor, endocrine therapy, and a taxane; patients received at least two prior chemotherapies in the metastatic setting (one of which could be in the neoadjuvant or adjuvant setting if recurrence occurred within 12 months). Patients were randomized (1:1) to receive TRODELVY 10 mg/kg as an intravenous infusion on Days 1 and 8 of a 21 day cycle (n=272) or single agent chemotherapy (n=271). Single agent chemotherapy was determined by the investigator before randomization from one of the following choices: eribulin (n=130), vinorelbine (n=63), gemcitabine (n=56), or capecitabine (n=22). Randomization was stratified by the following factors: prior chemotherapy regimens for metastatic disease (2 vs. 3–4), visceral metastasis (Yes or No), and endocrine therapy in the metastatic setting for at least 6 months (Yes or No). Patients were treated until disease progression or unacceptable toxicity. Administration of TRODELVY was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered by the investigator to be deriving clinical benefit. The primary efficacy outcome measure was PFS as determined by BICR per RECIST v1.1. Additional efficacy measures included OS, ORR by BICR, and DOR by BICR. The median age of patients in the study population was 56 years (range: 27–86 years), 26% of patients were 65 years or over. The majority of patients were female (99%); 67% were White, 4% were Black and 3% were Asian, and 26% were of unknown race. Patients received a median of 7 (range: 3 to 17) prior systemic regimens in any setting and 3 (range: 0 to 8) prior systemic chemotherapy regimens in the metastatic setting. Approximately 42% of patients had 2 prior chemotherapy regimens for treatment of metastatic disease compared to 58% of patients who had 3 to 4 prior chemotherapy regimens and all patients had an ECOG performance status of 0 (45%) or 1 (55%). Ninety-five percent of patients had visceral metastases. Most patients received endocrine therapy in the metastatic setting for ≥ 6 months (86%). TRODELVY demonstrated a statistically significant improvement in PFS and OS versus single agent chemotherapy. The efficacy results are summarized in Table 13 and Figure 3 and Figure 4. Table 13: Efficacy Results from TROPiCS-02 All Randomized Patients TRODELVY n=272 Single Agent Chemotherapy n=271 Progression-Free Survival by BICR PFS is defined as the time from the date of randomization to the date of the first radiological disease progression or death due to any cause, whichever comes first. Median PFS in months (95% CI) 5.5 (4.2, 7.0) 4.0 (3.1, 4.4) Hazard ratio (95% CI) 0.661 (0.529, 0.826) p-value Stratified log-rank test adjusted for stratification factors: prior chemotherapy regimens for metastatic disease (2 vs. 3–4), visceral metastasis (Y/N), and endocrine therapy in the metastatic setting for at least 6 months (Yes or No). BICR = Blinded Independent Central Review; CI = Confidence Interval 0.0003 Overall Survival Second interim OS analysis (conducted when 390 OS events were observed) Median OS in months (95% CI) 14.4 (13.0, 15.7) 11.2 (10.1, 12.7) Hazard ratio (95% CI) 0.789 (0.646, 0.964) p-value 0.0200 Objective Response Rate by BICR Response Rate, % (95% CI) 21.0 (16.3, 26.3) 14.0 (10.1, 18.7) Odds ratio (95% CI) 1.625 (1.034, 2.555) p-value 0.0348 Duration of Response (DOR) by BICR Median DOR in months (95% CI) 8.1 (6.7, 9.1) 5.6 (3.8, 7.9) Figure 3: Kaplan-Meier Plot of PFS by BICR in TROPiCS-02 Figure 4: Kaplan-Meier Plot of OS in TROPiCS-02 Figure 3 Figure 4 14.3 Locally Advanced or Metastatic Urothelial Cancer TROPHY Study The efficacy of TRODELVY was evaluated in TROPHY (NCT03547973), an single-arm, multicenter study that enrolled 112 patients with locally advanced or mUC who have received prior treatment with a platinum-containing chemotherapy and either PD-1 or PD-L1 inhibitor. Patients were administered TRODELVY 10 mg/kg as an intravenous infusion on Days 1 and 8 of a 21-day treatment cycle. Prior to the administration of TRODELVY, all patients were treated for prevention of chemotherapy induced nausea, vomiting and infusion reactions. Patients were treated until disease progression or unacceptable toxicity. The median age was 66 years (range: 33 to 90 years), 78% were male, 74% were White, 3% Asian, 3% Black and 20% unknown. All patients had a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 (28%) or 1 (72%). Ninety-six percent of patients had metastatic disease; 67% of patients had visceral metastases, including 34% with liver metastases. The median number of prior systemic therapies was 3 (range: 1 to 8). Sixty-five percent of patients received prior cisplatin, 21% received prior carboplatin, 13% received both prior cisplatin and carboplatin, and 100% received prior PD-1 or PD-L1 inhibitor. For 34% of patients, the platinum-containing chemotherapy was received in the neoadjuvant/adjuvant setting only. Nine percent of patients received prior enfortumab vedotin. The major efficacy outcome measures were the ORR and DOR, evaluated by Independent Review Assessment, using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Table 14 summarizes the efficacy results. Table 14: Efficacy results for patients with locally advanced or mUC in TROPHY TRODELVY (N=112) CI confidence interval + denotes ongoing Overall Response Rate by independent review assessment ORR (95% CI) 27.7% (19.6, 36.9) Complete response 5.4% Partial response 22.3% Response duration Number of responders 31 Median, Months (95% CI) 7.2 (4.7, 8.6) Range, Months 1.4+, 13.7
| All Randomized Patients | ||
|---|---|---|
| TRODELVY n=267 | Single Agent Chemotherapy n=262 | |
| CI = Confidence Interval | ||
| Disease Progression or Death (%) | 190 (71%) | 171 (65%) |
| Median PFS in months (95% CI) | 4.8 (4.1, 5.8) | 1.7 (1.5, 2.5) |
| Hazard ratio | 0.43 (0.35, 0.54) | |
| p-value | <0.0001 | |
| Deaths (%) | 179 (67%) | 206 (79%) |
| Median OS in months (95% CI) | 11.8 (10.5, 13.8) | 6.9 (5.9, 7.6) |
| Hazard ratio | 0.51 (0.41, 0.62) | |
| p-value | <0.0001 | |
| TRODELVY (N=108) | |
|---|---|
| CI: confidence interval | |
| +: denotes ongoing | |
| ORR (95% CI) | 33.3% (24.6, 43.1) |
| Complete response | 2.8% |
| Partial response | 30.6% |
| Number of responders | 36 |
| Median, Months (95% CI) | 7.7 (4.9, 10.8) |
| Range, Months | 1.9+, 30.4+ |
| % with duration ≥6 months | 55.6% |
| % with duration ≥12 months | 16.7% |
| All Randomized Patients | ||
|---|---|---|
| TRODELVY n=272 | Single Agent Chemotherapy n=271 | |
| Median PFS in months (95% CI) | 5.5 (4.2, 7.0) | 4.0 (3.1, 4.4) |
| Hazard ratio (95% CI) | 0.661 (0.529, 0.826) | |
| p-value | 0.0003 | |
| Median OS in months (95% CI) | 14.4 (13.0, 15.7) | 11.2 (10.1, 12.7) |
| Hazard ratio (95% CI) | 0.789 (0.646, 0.964) | |
| p-value | 0.0200 | |
| Response Rate, % (95% CI) | 21.0 (16.3, 26.3) | 14.0 (10.1, 18.7) |
| Odds ratio (95% CI) | 1.625 (1.034, 2.555) | |
| p-value | 0.0348 | |
| Median DOR in months (95% CI) | 8.1 (6.7, 9.1) | 5.6 (3.8, 7.9) |
| TRODELVY (N=112) | |
|---|---|
| CI confidence interval | |
| + denotes ongoing | |
| ORR (95% CI) | 27.7% (19.6, 36.9) |
| Complete response | 5.4% |
| Partial response | 22.3% |
| Number of responders | 31 |
| Median, Months (95% CI) | 7.2 (4.7, 8.6) |
| Range, Months | 1.4+, 13.7 |
References
This field may contain references when prescription drug labeling must summarize or otherwise relay on a recommendation by an authoritative scientific body, or on a standardized methodology, scale, or technique, because the information is important to prescribing decisions.15 REFERENCES 1. "OSHA Hazardous Drugs." OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html .
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.8.5 Geriatric Use Of the 366 patients with TNBC who were treated with TRODELVY, 19% of patients were 65 years and 3% were 75 years and older. No overall differences in safety and effectiveness were observed between patients ≥ 65 years of age and younger patients. Of the 322 patients with HR+/HER2- breast cancer who were treated with TRODELVY, 26% of patients were 65 years and older and 6% were 75 years and older. No overall differences in effectiveness were observed between patients ≥ 65 years of age and younger patients. There was a higher discontinuation rate due to adverse reactions in patients aged 65 years or older (14%) compared with younger patients (3%). Of the 180 patients with UC who were treated with TRODELVY, 59% of patients were 65 years and older and 27% were 75 years and older. No overall differences in effectiveness were observed between patients ≥ 65 years of age and younger patients. There was a higher discontinuation rate due to adverse reactions in patients aged 65 years or older (14%) compared with younger patients (8%).
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.8.4 Pediatric Use Safety and effectiveness of TRODELVY have not been established in pediatric patients.
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)8.1 Pregnancy Risk Summary Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. TRODELVY contains a genotoxic component, SN-38, and is toxic to rapidly dividing cells [see Clinical Pharmacology (12.1) and Nonclinical Toxicology (13.1) ] . Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 – 4% and 15 – 20%, respectively. Data Animal data There were no reproductive and developmental toxicology studies conducted with sacituzumab govitecan-hziy.
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. TRODELVY contains a genotoxic component, SN-38, and is toxic to rapidly dividing cells [see Clinical Pharmacology (12.1) and Nonclinical Toxicology (13.1) ] . Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 – 4% and 15 – 20%, respectively. Data Animal data There were no reproductive and developmental toxicology studies conducted with sacituzumab govitecan-hziy. 8.2 Lactation Risk Summary There is no information regarding the presence of sacituzumab govitecan-hziy or SN-38 in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 1 month after the last dose of TRODELVY. 8.3 Females and Males of Reproductive Potential Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to the initiation of TRODELVY. Contraception Females TRODELVY can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment with TRODELVY and for 6 months after the last dose. Males Because of the potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRODELVY and for 3 months after the last dose. Infertility Females Based on findings in animals, TRODELVY may impair fertility in females of reproductive potential [see Nonclinical Toxicology (13.1) ] . 8.4 Pediatric Use Safety and effectiveness of TRODELVY have not been established in pediatric patients. 8.5 Geriatric Use Of the 366 patients with TNBC who were treated with TRODELVY, 19% of patients were 65 years and 3% were 75 years and older. No overall differences in safety and effectiveness were observed between patients ≥ 65 years of age and younger patients. Of the 322 patients with HR+/HER2- breast cancer who were treated with TRODELVY, 26% of patients were 65 years and older and 6% were 75 years and older. No overall differences in effectiveness were observed between patients ≥ 65 years of age and younger patients. There was a higher discontinuation rate due to adverse reactions in patients aged 65 years or older (14%) compared with younger patients (3%). Of the 180 patients with UC who were treated with TRODELVY, 59% of patients were 65 years and older and 27% were 75 years and older. No overall differences in effectiveness were observed between patients ≥ 65 years of age and younger patients. There was a higher discontinuation rate due to adverse reactions in patients aged 65 years or older (14%) compared with younger patients (8%). 8.6 Hepatic Impairment No adjustment to the starting dosage is required when administering TRODELVY to patients with mild hepatic impairment [see Clinical Pharmacology (12.3) ] . The safety of TRODELVY in patients with moderate (total bilirubin > 1.5 to 3.0 × ULN) or severe (total bilirubin > 3.0 × upper limit of normal [ULN]) hepatic impairment has not been established. TRODELVY has not been tested in patients with AST or ALT > 3 ULN without liver metastases, or AST or ALT > 5 ULN with liver metastases. No recommendations can be made for the starting dosage in these patients.
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.16 HOW SUPPLIED/STORAGE AND HANDLING TRODELVY (sacituzumab govitecan-hziy) for injection is a sterile, off-white to yellowish lyophilized powder in a single-dose vial. Each TRODELVY vial is individually boxed in a carton: NDC 55135-132-01 contains one 180 mg vial Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of reconstitution. Do not freeze. TRODELVY is a hazardous drug. Follow applicable special handling and disposal procedures 1 .
Storage and handling
Information about safe storage and handling of the drug product.Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of reconstitution. Do not freeze. TRODELVY is a hazardous drug. Follow applicable special handling and disposal procedures 1 .
Boxed warning
Information about contraindications or serious warnings, particularly those that may lead to death or serious injury.WARNING: NEUTROPENIA AND DIARRHEA Severe or life threatening neutropenia may occur. Withhold TRODELVY for absolute neutrophil count below 1500/mm 3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis [see Dosage and Administration (2.3) ] . Initiate anti-infective treatment in patient with febrile neutropenia without delay [see Warnings and Precautions (5.1) ]. Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide [see Warnings and Precautions (5.2) ]. If severe diarrhea occurs, withhold TRODELVY until resolved to ≤ Grade 1 and reduce subsequent doses [see Dosage and Administration (2.3) ]. WARNING: NEUTROPENIA AND DIARRHEA See full prescribing information for complete boxed warning . Severe or life threatening neutropenia may occur. Withhold TRODELVY for absolute neutrophil count below 1500/mm 3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay. ( 2.3 , 5.1 ) Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold TRODELVY until resolved to ≤ Grade 1 and reduce subsequent doses. ( 2.3 , 5.2 )
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API