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.

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