733P - Efficacy and safety of sacituzumab govitecan (SG) in patients with advanced/metastatic endometrial cancer (EC): Updated results from TROPiCS-03

Background

Patients (pts) with advanced EC who progress on or after platinum (PT)-based chemotherapy (chemo) and immunotherapy (IO) have poor prognosis. SG is a Trop-2–directed antibody-drug conjugate that demonstrated encouraging efficacy and manageable safety in pts with metastatic, relapsed/refractory EC (Santin A et al; J Clin Oncol, 2023). We report updated results from TROPiCS-03.

Methods

This is a multicohort, open-label, phase 2 basket study in pts with metastatic solid tumors. Pts in the EC cohort had progressed after prior PT-based chemo and IO. Pts received SG 10 mg/kg on days 1 and 8 of a 21-day cycle. Primary end point was objective response rate (ORR) by investigator assessment per RECIST 1.1. Key secondary end points included clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS) per investigator assessment; overall survival (OS); safety.

Results

At data snapshot (March 8, 2024), this study enrolled 41 pts, with a median follow-up of 19.4 mo (range, 14.4-30.3). Median age was 68 years (range, 44-83), 20% of pts were microsatellite instability high, median prior lines of therapy was 3 (range, 1-6). ORR was 27% (95% CI, 14-43); median DOR was 9.0 mo (95% CI, 2.8-NR); median OS was 15.0 mo (95% CI, 5.9-NR) (table). Pts who previously received both PT-based chemo and IO (85%, n=35) had similar outcomes as the overall cohort. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 85% pts, most commonly neutropenia (49%), diarrhea (22%), and anemia (20%). Discontinuation rate due to TEAEs was 7%. Three pts had TEAEs leading to death (1, due to unknown cause, was deemed related to SG by the investigator).

Conclusions

In this first report of OS and with longer follow-up, SG shows promising clinical activity, with durable responses in pts pretreated with PT-based chemo with or without IO for advanced/metastatic EC. The safety profile was manageable, with low treatment discontinuation due to TEAEs. Table: 733P

Summary of efficacy endpoints

aPts without any post-baseline assessments are counted as not assessed.

bDuration ≥ 6 months for SD only.

cBased on patients who achieved a confirmed CR or PR. CR, complete response; NR, not reached; PR, partial response; SD, stable disease.

Clinical trial identification

NCT03964727.

Editorial acknowledgement

Medical writing and editorial support was provided by Priya Talluri, of Parexel.

Legal entity responsible for the study

Gilead Sciences, Inc.

Funding

Gilead Sciences, Inc.

Disclosure

B.R. Corr: Financial Interests, Institutional, Advisory Board: GSK, Gilead, ImmunoGen, Zentalis, Merck, Corcept, ImVax; Financial Interests, Institutional, Invited Speaker: Targeted Oncology; Financial Interests, Institutional, Coordinating PI: ImmunoGen, Clovis. E.E. Dumbrava: Financial Interests, Institutional, Other, Research/grant funding: Bayer HealthCare Pharmaceuticals, Immunocore Ltd, Amgen, Aileron Therapeutics, Compugen Ltd, Gilead, BOLT Therapeutics, Aprea Therapeutics, Bellicum, PMV Pharma, Triumvira, Seagen Inc, Mereo BioPharma 5 Inc, Sanofi, Rain Oncology, Astex Therapeutics, Sotio, Mersana Therapeutics, Poseida, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: PMV Pharma; Financial Interests, Personal, Advisory Board: BOLT Therapeutics, Mersana Therapeutics, Orum Therapeutics, Summit Therapeutics. A.I. Spira: Financial Interests, Personal, Other, Consulting or Advisory Role: Incyte, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Array Biopharma, Blueprint Medicines; Financial Interests, Personal, Other, Consulting or Advisory Role / Honoraria: Amgen, Novartis, Takeda, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, Janssen Oncology, Bayer; Financial Interests, Institutional, Officer, CEO: Next Oncology Virginia; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Local PI: LAM Therapeutics, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius, Synthekine, Mersana, Blueprint Medicines, Kezar, Revolution Med. L. Willmott: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Eisai, ImmunoGen, Merck, Seagen. J.E. Butrynski: Financial Interests, Personal, Other, Consultant as part of Ontada and US Oncology in Real World Experience in Dedifferentiated Liposarcoma: Boehringer Ingelheim; Financial Interests, Personal, Full or part-time Employment, Principal Investigator for Real World Experience in Dedifferentiated Liposarcoma at US Oncology: Ontada; Financial Interests, Institutional, Coordinating PI, National Principal investigator for US Oncology for trial of Sacituzumab Govitecan: Gilead. K.Y. Tse: Financial Interests, Personal, Invited Speaker: Zai Lab, GSK; Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca; Financial Interests, Institutional, Research Grant: Pfizer, Zai Lab, AstraZeneca; Financial Interests, Institutional, Coordinating PI: WKK Medical Equipment Co. Ltd. (Hong Kong); Financial Interests, Institutional, Local PI: Gilead; Non-Financial Interests, Leadership Role: Asia and Oceania Federation of Obstetrics and Gynecology Oncology committee. J. Patel: Financial Interests, Personal, Stocks/Shares: Gilead Sciences, Inc.. S. Mekan: Financial Interests, Institutional, Full or part-time Employment: Gilead Sciences. S. Mocci: Financial Interests, Personal, Full or part-time Employment, I am a full employee of the Company: Gilead. T. Wu: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences, Inc; Financial Interests, Personal, Stocks or ownership: Gilead Sciences, Inc. A.D. Santin: Financial Interests, Personal, Advisory Board: Merck, Eisai, Daiichi Sankyo, R-Pharm-US; Financial Interests, Institutional, Local PI: Merck, Verastem; Non-Financial Interests, Advisory Role: Merck, Eisai, Daiichi Sankyo, R-Pharm-USA.