TRODELVY

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 antiemet…

5 WARNINGS AND PRECAUTIONS Hypersensitivity and Infusion-Related Reactions: Hypersensitivity reactions including severe anaphylactic reactions have been observed. Monitor patients for infusion-related reactions. Permanently discontinue TRODELVY if severe or life-threatening reactions occur. ( 5.3 ) Nausea/Vomiting: Use antiemetic preventive treatment and withhold TRODELVY for patients with Grade 3 nausea or Grade 3–4 vomiting at the time of scheduled treatment. ( 5.4 ) Patients with Reduced UGT1A1 Activity: Individuals who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia following initiation of TRODELVY treatment. ( 5.5 ) Embryo-Fetal Toxicity: TRODELVY can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 ) 5.1 Neutropenia TRODELVY can cause severe, life-threatening, or fatal neutropenia as early as the first cycle of treatment. Neutropenia occurred in 64% of patients treated with TRODELVY. Grade 3–4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6% of patients. The median time to first onset of neutropenia (including febrile neutropenia) was 16 days (range: 1 to 435 days). Neutropenia occurred earlier in patients with reduced UGT1A1 activity [see Warnings and Precautions (5.5) ] . Neutropenic colitis occurred in 1.4% of patients. Primary prophylaxis with G-CSF is recommended starting in the first cycle of treatment in all patients at increased risk of febrile neutropenia, including older patients, patients with previous neutropenia, poor performance status, organ dysfunction, or multiple comorbidities. Monitor absolute neutrophil count (ANC) during treatment. Withhold TRODELVY for ANC below 1500/mm 3 on Day 1 of any cycle or below 1000/mm 3 on Day 8 of any cycle. Withhold TRODELVY for neutropenic fever. Dose modifications may be required due to neutropenia. Treat neutropenia with G-CSF and administer prophylaxis in subsequent cycles as clinically indicated or indicated in Table 2 [see Dosage and Administration (2.3) ] . 5.2 Diarrhea TRODELVY can cause severe diarrhea. Diarrhea occurred in 64% of all patients treated with TRODELVY. Grade 3–4 diarrhea occurred in 11% of all patients treated with TRODELVY. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold TRODELVY for Grade 3–4 diarrhea at the time of scheduled treatment administration and resume when resolved to ≤ Grade 1 [see Dosage and Administration (2.3) ]. At the onset of diarrhea, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment with TRODELVY (e.g., abdominal cramping, diarrhea, salivation, etc.) can receive appropriate premedication (e.g., atropine) for subsequent treatments. 5.3 Hypersensitivity and Infusion-Related Reactions TRODELVY can cause serious hypersensitivity reactions including life-threatening anaphylactic reactions. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions [see Contraindications (4) ] . Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients treated with TRODELVY. Grade 3–4 hypersensitivity occurred in 2% of patients treated with TRODELVY. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.2%. The incidence of anaphylactic reactions was 0.2%. Premedication for infusion reactions in patients receiving TRODELVY is recomme…

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 )

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.

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.

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.

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 frequ…