Sacituzumab Govitecan

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 ) 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.

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 ) Primary prophylaxis with G-CSF is recommended starting in the first cycle in all patients at increased risk of febrile neutropenia. ( 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). Prophylaxis for Neutropenia Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) is recommended starting in the first cycle for all patients at increased risk of febrile neutropenia [see Warnings and Precautions (5.1) ] . 2.3 Dose Modifications for Adverse Reactions Management of adverse reactions may require temporary interruption, dose reduction, or treatment discontinuation of TRODELVY as described in Tables 1 and 2. Do not re-escalate the TRODELVY dose after a dose reduction for adverse reactions has been made. Table 1: Dosage Reduction Levels Dose Level Dosage and Schedule Recommended starting dose 10 mg/kg once weekly on Days 1 and 8 of 21-day treatment cycles First dose reduction Reduce to 7.5 mg/kg Second dose reduction Reduce to 5 mg/kg Requirement for further dose reduction Permanently discontinue TRODELVY The recommended dosage modifications for adverse reactions are provided in Table 2. Table 2: Dose Modifications for Adverse Reactions Adverse reactions Severity Dose Modification Neutropenia [see Warnings and Precautions (5.1) ] Grade 3–4 neutropenia (Absolute Neutrophil Count [ANC] <1000/mm 3 ) or febrile neutropenia Withhold TRODELVY until ANC ≥1500/mm 3 for Day 1 dose or ANC ≥1000/mm 3 for Day 8 Dose Administer G-CSF during treatment as clinically indicated. Reduce one dose level for each occurrence of febrile neutropenia or prolonged Grade 3–4 neutropenia, or discontinue according to Table 1. Nausea/Vomiting/ Diarrhea [see Warnings and Precautions (5.2 , 5.4) ] Grade 3–4 nausea, vomiting or diarrhea that is not controlled with antiemetics or anti-diarrheal agents Withhold TRODELVY until resolved to ≤ Grade 1 Reduce one dose level with each occurrence, or discontinue according to Table 1. Infusion-Related Reaction [see Warnings and Precautions (5.3) ] Grade 1–3 infusion-related reactions Slow infusion rate or interrupt the infusion Grade 4 infusion-related reactions Discontinue TRODELVY. Other Toxicities Other Grade 3–4 toxicities of any duration despite optimal medical management Withhold TRODELVY until resolved to ≤ Grade 1 Reduce one dose level with each occurrence or discontinue according to Table 1. 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 current body weight [see Dosage and Administration (2.2) ] . 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.

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, which included 366 patients with mTNBC and 322 patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer from IMMU-132-01, ASCENT, and TROPiCS-02; and 375 patients with other tumor types. 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 3 and 4 summarize adverse reactions and laboratory abnormalities, respectively, in the ASCENT study. Table 3: 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 4: 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 5 and 6 summarize adverse reactions and laboratory abnormalities occurring in ≥ 10% of patients with mTNBC in the IMMU-132-01 study. Table 5: 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 6: 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 7 and 8 summarize adverse reactions and laboratory abnormalities in the TROPiCS-02 study. Table 7: 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 8: 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

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 9. Table 9: 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 and 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) ] .