Safety

4CONTRAINDICATIONS

TRODELVY is contraindicated in patients who have experienced a severe hypersensitivity reaction to TRODELVY [see Warnings and Precautions (5.3)].

5WARNINGS AND PRECAUTIONS

5.1 Neutropenia

TRODELVY can cause severe or life-threatening neutropenia. Withhold TRODELVY for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold TRODELVY for neutropenic fever. Dose modifications may be required due to neutropenia [see Dosage and Administration (2.3)].

Febrile neutropenia occurred in 6% (24/408) patients treated with TRODELVY, including 8% (9/108) patients with mTNBC after at least two prior therapies. Less than 1% (1/408) of patients had febrile neutropenia leading to permanent discontinuation.

The incidence of Grade 1-4 neutropenia was 64% in patients with mTNBC (n=108). In all patients treated with TRODELVY (n=408), the incidence of Grade1-4 neutropenia was 54%; Grade 4 neutropenia occurred in 13%. Less than 1% (2/408) of patients permanently discontinued treatment due to neutropenia.

5.2 Diarrhea

TRODELVY can cause severe diarrhea. 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.

Diarrhea occurred in 63% (68/108) of patients with mTNBC and 62% (254/408) of all patients treated with TRODELVY. In each population, events of Grade 3-4 occurred in 9% (10/108) of mTNBC patients and 9% (36/408) of all patients treated with TRODELVY. Four out of 408 patients (<1%) discontinued treatment because of diarrhea. Neutropenic colitis was observed in 2% (2/108) of patients in the mTNBC cohort and 1% of all patients treated with TRODELVY.

5.3 Hypersensitivity

TRODELVY can cause severe and life-threatening hypersensitivity. Anaphylactic reactions have been observed in clinical trials with TRODELVY.

Hypersensitivity reactions within 24 hours of dosing occurred in 37% (151/408) of patient treated with TRODELVY. Grade 3-4 hypersensitivity occurred in 1% (6/408) of patients treated with TRODELVY. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 1% (3/408).

Pre-infusion medication for patients receiving TRODELVY is recommended. Observe patients closely for infusion-related reactions during each TRODELVY infusion and for at least 30 minutes after completion of each infusion [see Dosage and Administration (2.3)]. Medication to treat such reactions, as well as emergency equipment, should be available for immediate use.

5.4 Nausea and Vomiting

TRODELVY is emetogenic. Nausea occurred in 69% (74/108) of patients with mTNBC and 69% (281/408) of all patients treated with TRODELVY. Grade 3 nausea occurred in 6% (7/108) and 5% (22/408) of these populations, respectively.

Vomiting occurred in 49% (53/108) of patients with mTNBC and 45% (183/408) of all patients treated with TRODELVY. Grade 3 vomiting occurred in 6% (7/108) and 4% (16/408) of these patients, respectively.

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) for prevention of chemotherapy-induced nausea and vomiting (CINV).

Withhold TRODELVY doses for Grade 3 nausea or Grade 3-4 vomiting at the time of scheduled treatment administration and resume with additional supportive measures when resolved to Grade ≤ 1 [see Dosage and Administration (2.3)].

Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

5.5 Use in 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 and may be at increased risk for other adverse reactions following initiation of TRODELVY treatment.

In 84% (343/408) of patients who received TRODELVY (up to 10 mg/kg on Days 1 and 8 of a 21-day cycle) and had retrospective UGT1A1 genotype results available, the incidence of Grade 4 neutropenia was 26% (10/39) in patients homozygous for the UGT1A1*28 allele, 13% (20/155) in patients heterozygous for the UGT1A1*28 allele and 11% (16/149) in patients homozygous for the wild-type allele [see Clinical Pharmacology (12.5)].

Closely monitor patients with reduced UGT1A1 activity for severe neutropenia. The appropriate dose for patients who are homozygous for UGT1A1*28 is not known and should be considered based on individual patient tolerance to treatment [see Dosage and Administration (2.3)].

5.6 Embryo-Fetal Toxicity

Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. TRODELVY contains a genotoxic component, SN-38, and targets 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. Advise females of reproductive potential to use effective contraception during treatment with TRODELVY and for 6 months after the last dose. 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 [see Use in Specific Populations (8.1), (8.3)].

6ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the label:

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 data described in the Warnings and Precautions section reflect exposure to TRODELVY as a single agent in a single-arm, open-label study (IMMU-132-01) in 408 patients with mTNBC and other malignancies who had received prior systemic therapeutic regimen for advanced disease. 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 data in Table 2 reflect exposure to TRODELVY in a subset of 108 patients with mTNBC who had received at least two prior treatments for metastatic disease in study (IMMU-132-01). Patients received TRODELVY 10 mg/kg via intravenous infusion on Days 1 and 8 of 21-day treatment cycles until disease progression or unacceptable toxicity. The median treatment duration in these 108 patients was 5.1 months (range: 0-51 months).

Serious adverse reactions were reported in 31% of the patients. The most frequent serious adverse reactions (reported in >1%) of the patients receiving TRODELVY were 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 discontinuation were anaphylaxis, anorexia/fatigue, headache (each <1%, 1 patient for each event). 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.

Adverse reactions occurring in ≥10% of patients with mTNBC in the IMMU-132-01 study are summarized in Table 2.

Table 2: Adverse Reactions in ≥ 10% of Patients with mTNBC in IMMU-132-01
Adverse ReactionTRODELVY (n=108)
Grade 1-4 (%)Grade 3-4 (%)
Any adverse reaction10071
Gastrointestinal disorders9521
Nausea696
Diarrhea639
Vomiting496
Constipation341
Abdominal paini261
Mucositisii141
General disorders and administration site conditions779
Fatigueiii578
Edemaiv190
Pyrexia140
Blood and lymphatic system disorders7437
Neutropenia6443
Anemia5212
Thrombocytopenia143
Metabolism and nutrition disorders6822
Decreased appetite301
Hyperglycemia244
Hypomagnesemia211
Hypokalemia192
Hypophosphatemia169
Dehydration135
Skin and subcutaneous tissue disorders634
Alopecia380
Rashv313
Pruritus170
Dry Skin150
Nervous system disorders564
Headache231
Dizziness220
Neuropathyvi240
Dysgeusia110
Infections and infestations5512
Urinary Tract Infection213
Respiratory Infectionvii263
Musculoskeletal and connective tissue disorders541
Back pain230
Arthralgia170
Pain in extremity110
Respiratory, thoracic and mediastinal disorders545
Coughviii220
Dyspneaix213
Psychiatric disorders261
Insomnia130

Graded per NCI CTCAE v. 4.0

i Including abdominal pain, distention, pain (upper), discomfort, tenderness

ii Including stomatitis, esophagitis, and mucosal inflammation

iii Including fatigue and asthenia

iv Including edema; and peripheral, localized, and periorbital edema

v Including rash; maculopapular, erythematous, generalized rash; dermatitis acneiform; skin disorder, irritation, and exfoliation

vi Including gait disturbance, hypoesthesia, muscular weakness, paresthesia, peripheral and sensory neuropathy

vii Including lower and upper respiratory tract infection, pneumonia, influenza, viral upper respiratory infection, bronchitis and respiratory syncytial virus infection

viii Includes cough and productive cough

ix Includes dyspnea and exertional dyspnea


Table 3: Laboratory Abnormalities observed in >10% of Patients while receiving TRODELVY
Laboratory AbnormalityTRODELVY (n=108)
All Grades (%)Grade 3-4 (%)
Hematology
Decreased hemoglobin936
Decreased leukocytes9126
Decreased neutrophils8232
Increased activated partial thromboplastin time6012
Decreased platelets303
Chemistry
Increased alkaline phosphatase572
Decreased magnesium513
Decreased calcium493
Increased glucose483
Increased aspartate aminotransferase453
Decreased albumin391
Increased alanine aminotransferase352
Decreased potassium303
Decreased phosphate295
Decreased sodium254.7
Increased magnesium244
Decreased glucose192

6.2 Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other sacituzumab govitecan products may be misleading.

The analysis of immunogenicity of TRODELVY in serum samples from 106 patients with mTNBC was evaluated using an electrochemiluminescence (ECL)-based immunoassay to test for anti-sacituzumab govitecan-hziy antibodies. Detection of the anti-sacituzumab govitecan-hziy antibodies was done using a 3-tier approach: screen, confirm, and titer. Persistent anti-sacituzumab govitecan-hziy antibodies developed in 2% (2/106) of patients.

7DRUG INTERACTIONS

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 substantially 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.

Next: Additional Risk Info
INDICATION

TRODELVY™ (sacituzumab govitecan-hziy) is indicated for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION
WARNING: NEUTROPENIA AND DIARRHEA

Severe neutropenia may occur. Withhold TRODELVY for absolute neutrophil count below 1500/mm3 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.

Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. Administer atropine, if not contraindicated, for early diarrhea of any severity. At the onset of late 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.

Contraindications

TRODELVY is contraindicated in patients who have experienced a severe hypersensitivity reaction to TRODELVY.

Hypersensitivity

TRODELVY can cause severe and life-threatening hypersensitivity. Anaphylactic reactions have been observed in clinical trials with TRODELVY.

Hypersensitivity reactions within 24 hours of dosing occurred in 37% (151/408) of patients treated with TRODELVY. Grade 3-4 hypersensitivity occurred in 1% (6/408) of patients treated with TRODELVY. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 1% (3/408).

Pre-infusion medication for patients receiving TRODELVY is recommended. Observe patients closely for infusion-related reactions during each TRODELVY infusion and for at least 30 minutes after completion of each infusion. Medication to treat such reactions, as well as emergency equipment, should be available for immediate use.

Nausea and Vomiting

TRODELVY is emetogenic. Nausea occurred in 69% (74/108) of patients with mTNBC and 69% (281/408) of all patients treated with TRODELVY. Grade 3 nausea occurred in 6% (7/108) and 5% (22/408) of these populations, respectively.

Vomiting occurred in 49% (53/108) of patients with mTNBC and 45% (183/408) of all patients treated with TRODELVY. Grade 3 vomiting occurred in 6% (7/108) and 4% (16/408) of these patients, respectively.

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) for prevention of chemotherapy-induced nausea and vomiting (CINV).

Withhold TRODELVY doses for Grade 3 nausea or Grade 3-4 vomiting at the time of scheduled treatment administration and resume with additional supportive measures when resolved to Grade ≤1.

Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Use in 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 and may be at increased risk for other adverse reactions following initiation of TRODELVY treatment.

In 84% (343/408) of patients who received TRODELVY (up to 10 mg/kg on Days 1 and 8 of a 21-day cycle) and had retrospective UGT1A1 genotype results available, the incidence of Grade 4 neutropenia was 26% (10/39) in patients homozygous for the UGT1A1*28 allele, 13% (20/155) in patients heterozygous for the UGT1A1*28 allele and 11% (16/149) in patients homozygous for the wild-type allele.

Closely monitor patients with reduced UGT1A1 activity for severe neutropenia. The appropriate dose for patients who are homozygous for UGT1A1*28 is not known and should be considered based on individual patient tolerance to treatment.

Embryo-Fetal Toxicity

Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. TRODELVY contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRODELVY and for 6 months after the last dose. 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.

Lactation

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.

Adverse Reactions

Most common adverse reactions (incidence ≥25%) in patients with mTNBC are nausea (69%), neutropenia (64%), diarrhea (63%), fatigue (57%), anemia (52%), vomiting (49%), alopecia (38%), constipation (34%), rash (31%), decreased appetite (30%), abdominal pain (26%), and respiratory infection (26%).

Please see full Prescribing Information, including boxed Warning, and Patient Information.