Trodelvy Drug Information

Important Use Information and Premedication Do

NOT substitute TRODELVY for or use with other drugs containing irinotecan or its active metabolite SN-38. Premedication Prior to each dose of TRODELVY, premedication for prevention of infusion reactions and 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 2 or 3 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.

Patient Selection for Combination Therapy

Select patients for treatment of unresectable locally advanced or metastatic TNBC with TRODELVY in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, based on the tumor expression of PD-L1 as confirmed by an FDA-authorized test. Information on FDA-authorized tests is available at http://www.fda.gov/companiondiagnostics.

Recommended Dosage

The recommended dosage of TRODELVY as a single agent or in combination with pembrolizumab is 10 mg/kg administered as an intravenous infusion on Days 1 and 8 of each 21-day cycle. Continue TRODELVY until disease progression or unacceptable toxicity. Do not administer TRODELVY at doses greater than 10 mg/kg.

When TRODELVY is administered in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, discontinue pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, after approximately 24 months. Refer to the Prescribing Information for pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph for the recommended dosing information.

Dosage Modifications for Adverse Reactions Management of adverse reactions may require temporary interruption, dose reduction, or permanent 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 The recommended dosage modifications for adverse reactions are provided in Table 2.

Table 2: Dosage Modifications for Adverse Reactions Adverse reactions Severity Dose Modification Neutropenia Grade 3-4 neutropenia (Absolute Neutrophil Count <1,000/mm 3 ) or febrile neutropenia Dosage Modifications for Adverse Reactions for TRODELVY in Combination with Pembrolizumab or Pembrolizumab and berahyaluronidase alfa-pmph Interrupt or discontinue one or both drugs of the combination or reduce the dose of TRODELVY to manage adverse reactions as appropriate. Refer to the prescribing information for pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph for recommendations on dosage interruption or discontinuation due to adverse reactions.

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.

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 reconstituted TRODELVY 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.

First infusion: Administer 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. Second and subsequent infusions: Administer over 1 to 2 hours if prior infusions were tolerated.

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 in the same intravenous line, with other medicinal products. Upon completion of the infusion, flush the intravenous line with 20 mL 0.9% Sodium Chloride Injection, USP.

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 as a single agent in 1354 patients, which included 641 patients with mTNBC and 322 patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer from ASCENT-03, IMMU-132-01, ASCENT, and TROPiCS-02; and 391 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.

In this pooled safety population, the most common (> 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count ( %). The data described in the following section reflects exposure to TRODELVY in combination with intravenous pembrolizumab in 221 patients with PD-L1 positive TNBC from ASCENT-04. Locally Advanced or Metastatic Triple-Negative Breast Cancer (TNBC) Single-Agent in Previously Untreated Unresectable Locally Advanced or Metastatic TNBC (ASCENT-03) The safety of TRODELVY was evaluated in 275 patients with unresectable locally advanced or metastatic TNBC who had not received previous systemic therapy for advanced disease and who were not candidates for PD-1 or PD-L1 inhibitor therapy who had received at least one dose of TRODELVY 10 mg/kg in ASCENT-03.

The median duration of treatment was 8.3 months (range: 0 to 29 months). Serious adverse reactions occurred in 26% of patients receiving TRODELVY. Serious adverse reactions in > 2% of patients included diarrhea, febrile neutropenia, and neutropenia (3.6% each) and pneumonia (2.9%).

Fatal adverse reactions occurred in 2.5% of patients who received TRODELVY including sepsis (1.1%) and acute respiratory failure, neutropenic colitis, pneumonia, and septic shock (0.4% each). Permanent discontinuation of TRODELVY due to adverse reactions occurred in 3.6% of patients, of which interstitial lung disease accounted for 1.1%. Dosage interruptions of TRODELVY occurred in 66% of patients.

Dose reductions of TRODELVY due to an adverse reaction occurred in 37% of patients. Tables 3 and 4 summarize the adverse reactions and laboratory abnormalities in ASCENT-03. Table 3: Adverse Reactions in ≥ 10% of Patients with Metastatic TNBC in ASCENT-03 % of Patients with Metastatic TNBC in ASCENT-03 0 4 0 In Combination with Pembrolizumab in Previously Untreated, Unresectable Locally Advanced or Metastatic TNBC whose tumors express PD-L1 (ASCENT-04) The safety of TRODELVY in combination with pembrolizumab was evaluated in 221 patients with unresectable locally advanced or metastatic TNBC who have not received previous systemic therapy for advanced disease and whose tumors express PD-L1 who received at least one dose of TRODELVY 10 mg/kg in combination with pembrolizumab.

The median duration of treatment of TRODELVY was 8.9 months (range: 0 to 27 months ). Fatal adverse reactions occurred in 3.2% of patients who received TRODELVY in combination with pembrolizumab including death (unknown cause) (0.9%) and completed suicide, neutropenic sepsis, sepsis, pneumonia, and pulmonary embolism (0.5% each). Permanent discontinuation of TRODELVY due to an adverse reaction occurred in 7% of patients.

Adverse reactions which resulted in permanent discontinuation of TRODELVY in ≥1% of patients included infusion related reaction (0.9%). Dosage interruptions of TRODELVY due to an adverse reaction occurred in 75% of patients. Dose reduction of TRODELVY due to an adverse reaction occurred in 35% of patients.

G-CSF was used in 63% of patients who received TRODELVY in combination with pembrolizumab. Tables 5 and 6 summarize the adverse reactions and laboratory abnormalities in ASCENT-04. Table 5: Adverse Reactions in ≥ 10% of Patients Receiving TRODELVY in Combination with Intravenous Pembrolizumab with Metastatic TNBC in ASCENT-04 % of Patients Receiving TRODELVY in Combination with Intravenous Pembrolizumab with Metastatic TNBC in ASCENT-04 Previously Treated Locally Advanced or Metastatic TNBC (ASCENT) The safety of TRODELVY was evaluated in 258 patients with metastatic TNBC who had previously received a taxane and at least two prior chemotherapies and who received at least one dose of TRODELVY 10 mg/kg in ASCENT.

The median duration of treatment was 4.4 months (range: 0 to 23 months). Adverse reactions which resulted in permanent discontinuation of TRODELVY in ≥1% of patients included pneumonia and fatigue (1% each). Adverse reactions which required a dose reduction in >4% of patients included neutropenia (11%) and diarrhea (5%).

Granulocyte-colony stimulating factor (G-CSF) was used in 44% of patients who received TRODELVY. Tables 7 and 8 summarize adverse reactions and laboratory abnormalities, respectively, in ASCENT. The median duration of treatment was 5.1 months (range: 0 to 51 months).

A fatal adverse reaction of metastases to spine occurred in 1 patient (0.9%) who received TRODELVY. Adverse reactions which resulted in permanent discontinuation of TRODELVY included anaphylaxis, decreased appetite, fatigue, and localized edema (each 0.9%). Adverse reactions which required dose reductions most commonly included neutropenia/febrile neutropenia.

Table 9: Adverse Reactions in ≥ 10% of Patients with Metastatic TNBC in IMMU-: Laboratory Abnormalities observed in > 10% of Patients with Metastatic TNBC in IMMU- Locally Advanced or Metastatic HR-Positive, HER2-Negative Breast Cancer TROPiCS-02 The safety of TRODELVY was evaluated in 268 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) who had received at least one dose of TRODELVY 10 mg/kg in TROPiCS-02. Serious adverse reactions occurred in 28% of patients who received TRODELVY. Fatal adverse reactions occurred in 2.2% of patients who received TRODELVY including arrhythmia, COVID-19 pneumonia, pneumonia, nervous system disorder, pulmonary embolism, and septic shock (0.4% each).

Adverse reactions which resulted in permanent discontinuation of TRODELVY in ≥ 0.5% of patients included asthenia, general physical health deterioration, and neutropenia (0.7% each). Adverse reactions which required dosage interruption in ≥ 5% of patients included neutropenia (50%). Adverse reactions which required dose reductions in >5% of patients included neutropenia (16%) and diarrhea (8%).

The most common (≥ 25%) adverse reactions, including laboratory abnormalities, were decreased leukocyte count summarize adverse reactions and laboratory abnormalities in TROPiCS-02.

Effect of Other Drugs on TRODELVY UGT1A1 Inhibitors

Avoid administering UGT1A1 inhibitors with TRODELVY. SN-38 is a UGT1A1 substrate. 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.

UGT1A1 Inducers Avoid administering UGT1A1 inducers with TRODELVY. Concomitant administration of TRODELVY with inducers of UGT1A1may reduce exposure to SN-38.

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.

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 respectively.

Data Animal data There were no reproductive and developmental toxicology studies conducted with sacituzumab govitecan-hziy.

Pediatric Use Safety and effectiveness of TRODELVY have not been established in pediatric patients.

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

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.