Trodelvy® (sacituzumab govitecan-hziy)

First-Line Use in Cisplatin- or Platinum‑Ineligible mUC

This document is in response to your request for information regarding Trodelvy® (sacituzumab govitecan-hziy [SG]) and its use in the first-line setting in patients with locally advanced or metastatic urothelial cancer (mUC) who are ineligible for cisplatin (cis)- or platinum-based therapy.

Some data may be outside of the US FDA-approved prescribing information. In providing this data, Gilead Sciences, Inc. is not making any representation as to its clinical relevance or to the use of any Gilead product(s). For information about the approved conditions of use of any Gilead drug product, please consult the FDA-approved prescribing information.

Trodelvy is not indicated for use in patients with mUC. The full indication, important safety information, and boxed warnings for neutropenia and diarrhea are available at: www.gilead.com/-/media/gileadcorpredesign/project/gilead/gileadcorporate/medicines/pdf/trodelvy_pi.

Summary

Combination Therapy With SG in First-Line Treatment of Cis-Ineligible mUC

A phase 1/2 non-randomized study evaluated the efficacy and safety of SG in combination with ipilimumab (IPI) + nivolumab (NIVO) in patients with treatment-naïve, locally advanced or mUC who are ineligible to receive cis-based chemotherapy.1,2  

• The recommended phase 2 dose (RP2D) from phase 1 was IPI 3 mg/kg + NIVO 1 mg/kg every 3 weeks for 4 cycles, followed by NIVO 3 mg/kg every 3 weeks + SG 8 mg/kg on Days 1 and 8 every 3 weeks.2
• In phase 2, the median progression-free survival (PFS) was 12.72 months (95% CI: 9.17–not assessable [NA]), the duration of best response was 8.04 months, and the median overall survival (OS) was NA (95% CI: 11.05 months–NA) among the 18 patients with evaluable efficacy data at a median follow-up of 21.57 months.2
• The trial was terminated early due to 2 events of Grade 5 immune-mediated myocarditis. The most common any-grade treatment-related adverse events (TRAEs) were diarrhea (72%), rash (56%), fatigue (56%), neutropenia (52%), and nausea (52%).2

Combination Therapy With SG in First-Line Treatment of Cis‑Ineligible mUC

IPI + NIVO With SG as First-Line Treatment for Cis-Ineligible mUC

Study design and demographics

A phase 1/2, non-randomized study evaluated the efficacy and safety of SG in combination with IPI + NIVO in patients with treatment-naïve, locally advanced or mUC who are ineligible to receive cis-based chemotherapy.1

Phase 1 (N=9) evaluated the feasibility and tolerability of escalating doses of IPI + NIVO + SG to determine the maximum tolerated dose and the RP2D of the combination. In phase 1, patients were given fixed doses of IPI 3 mg/kg + NIVO 1 mg/kg every 3 weeks for 4 cycles, followed by NIVO 360 mg IV every 3 weeks. Beginning at Cycle 1, IV SG 8 mg/kg (Dose Level 1) was administered on Days 1 and 8 every 3 weeks with an allowance of 1 dose escalation to 10 mg/kg (Dose Level 2) and 1 dose reduction to 6 mg/kg. Three patients experienced DLTs: 2 who received SG 10 mg/kg (Grade 3 pneumonitis and Grade 3 skin rash) and 1 who received SG 8 mg/kg (Grade 3 skin rash).1

In phase 2, 16 patients received the RP2D of IPI 3 mg/kg + NIVO 1 mg/kg every 3 weeks for 4 cycles, followed by NIVO 3 mg/kg every 3 weeks + SG 8 mg/kg on Days 1 and 8 every 3 weeks. The objectives were objective response rate (ORR), PFS, OS, and DOR.2 Baselined demographics and disease characteristics of the patients in phase 1/2 are summarized in Table 1.

Table 1. Phase 1/2 Study of IPI + NIVO Followed by NIVO + SG:
Baseline Demographics and Disease Characteristics2

Abbreviation: ECOG PS=Eastern Cooperative Oncology Group Performance Status.

Results2

With a median follow up of 21.57 months, the ORR in the efficacy analysis set (n=18) was 83.3%. Six patients had a complete response, 9 patients had a partial response, 1 patient had progressive disease (ie, emergence of a new lesion with a reduction of the target lesion), and 2 patients had stable disease. The median PFS was 12.72 months (95% CI: 9.17–NA), and the median OS was NA (95% CI: 11.05–NA). The duration of best response was 8.04 months.

The trial was terminated early due to 2 events of Grade 5 immune-mediated myocarditis. The most common (>20%) any-grade and Grade ≥3 TRAEs are presented in Table 2.

Table 2. Phase 1/2 Study of IPI + NIVO Followed by NIVO + SG:
Most Common (>20%) TRAEs2

References

1. Jain RK, Yang Y, Chadha J, et al. Phase I/II study of Ipilimumab plus Nivolumab (IPI-NIVO) combined with sacituzumab govitecan in patients with metastatic cisplatin-ineligible urothelial carcinoma [Poster 521]. Paper presented at: American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium; 16-18 February, 2023; San Francisco, CA.

2. Jain RK, Ong F, Chatwal M, et al. Phase 1/2 study of ipilimumab plus nivolumab (IPI-NIVO) combined with sacituzumab govitecan in patients with metastatic cisplatin-ineligible urothelial carcinoma (Poster #1969P). Paper presented at: European Society for Medical Oncology (ESMO); September 13-17, 2024; Barcelona, Spain.

Product Label

For the full indication, important safety information, and boxed warning(s), please refer to the Trodelvy US Prescribing Information available at: www.gilead.com/-/media/gileadcorpredesign/project/gilead/gileadcorporate/medicines/pdf/trodelvy_pi.

Follow-Up

For any additional questions, please contact Trodelvy Medical Information at:

☎1‐888-983-4668 or   www.askgileadmedical.com

Adverse Event Reporting

Please report all adverse events to:

Gilead Global Patient Safety ☎ 1-800-445-3235, option 3 or
 www.gilead.com/utility/contact/report-an-adverse-event

FDA MedWatch Program by ☎ 1-800-FDA-1088 or MedWatch, FDA, 5600 Fishers Ln, Rockville, MD 20852 or   www.accessdata.fda.gov/scripts/medwatch

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