1990MO - Sacituzumab govitecan (SG) as second-line (2L) treatment for extensive stage small cell lung cancer (ES-SCLC): Preliminary results from the phase II TROPiCS-03 basket trial

Background

Treatment options are limited for patients (pts) with ES-SCLC that progresses after anti-programmed death ligand 1 (PD-L1) therapy and chemotherapy (chemo). SG, a Trop-2-directed antibody-drug conjugate, demonstrated antitumor activity in previously treated ES-SCLC in a phase 1/2 study (Bardia, et al. Ann Oncol. 2021). TROPiCS-03 (NCT03964727) is an open-label, multicohort, phase 2 study evaluating SG in pts with metastatic or locally advanced solid tumors. Here, we report preliminary results from the ES-SCLC cohort.

Methods

Adult pts with ES-SCLC that progressed after no more than 1 prior line of platinum-based chemo and anti-PD-(L)1 therapy received SG 10 mg/kg on Days 1 and 8 of a 21-day cycle. The primary endpoint was objective response rate (ORR) by investigator assessment (INV) per RECIST v1.1. Key secondary endpoints included clinical benefit rate (CBR), duration of response, progression-free survival, overall survival, and safety. Pts who received ≥1 dose of SG were included in the safety analysis and pts who received ≥1 dose of SG and had ≥13.0 weeks of follow-up were included in the efficacy analysis.

Results

As of 18 April 2023, 26 pts received ≥1 dose of SG. Median age was 67 years (range, 48-79) and 89% of pts had an ECOG performance status of 1. Median follow-up was 3.5 months (range, 0.6-9.4). Treatment was ongoing for 16 (62%) pts. In the efficacy analysis (n=14), ORR was 29% and CBR was 36% (Table). In the safety analysis (n=26), any-grade treatment-related adverse events (TRAEs) occurred in 96% (grade ≥3, 46%) of pts. No TRAEs leading to discontinuation of study treatment were reported to date. No deaths due to AEs were reported to date.

Conclusions

SG as 2L treatment for ES-SCLC demonstrated promising antitumor activity and manageable safety, with no TRAEs leading to discontinuation reported to date. Additional data with more pts and longer follow-up will be presented.

Table: 1990MO

^aBy INV. ^bPts with CR + PR + SD for ≥ 6 months. BOR, best overall response; CI, confidence interval; CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease.

Clinical trial identification

NCT03964727.

Editorial acknowledgement

Editorial support was provided by Dominic Singson, MD of Parexel and funded by Gilead Sciences, Inc.

Legal entity responsible for the study

Gilead Sciences, Inc.

Funding

Gilead Sciences, Inc.

Disclosure

A. Dowlati: Financial Interests, Personal, Advisory Board: Ipsen, BMS, AstraZeneca, Seattle genetics, PUMA, Prelude. A. Cervantes: Financial Interests, Institutional, Advisory Board: Merck Serono, Amgen, Roche, Transgene, AnHeart Therapeutics, AbbVie, GSK; Financial Interests, Institutional, Invited Speaker: Amgen, Roche, Merck Serono, Foundation Medicine; Financial Interests, Personal, Other, Associate Editor: Annals of Oncology, ESMO Open; Financial Interests, Personal, Other, Editor in Chief: Cancer Treatment Reviews; Financial Interests, Institutional, Research Grant, Principal Investigator: Actuate Therapeutic, Amgen, Astellas Pharma, BeiGene, Bayer, AstraZeneca, BMS, Amcure, FibroGen, Lilly, Genentech, MedImmune, Merck Serono, Novartis, Natera, MSD, Servier, Sierra Oncology, Adaptimmune, Takeda, Affimed, Roche, Seamless, Gilead, Janssen, F. STAR Therapeutics, Ribon Therapeutics; Non-Financial Interests, Other, Scientific Director: INCLIVA Biomedical Research Institute. S. Babu: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Pharmacosmos, BeiGene, Kite, A Gilead Company, Janssen Oncology, Amgen; Financial Interests, Personal, Ownership Interest: MirusMD; Financial Interests, Institutional, Local PI, Institutional Ownership: BMS; Financial Interests, Institutional, Local PI, Shared Institutional Ownership: Novartis, Genentech/Roche, AstraZeneca/Medimmune, Janssen Oncology, Amgen, TG THerepeutics, AbbVie, Eli Lilly, Merck, Syndax, Sanofi, BeiGene, TORL Pharmaceuticals, Aptose, Argenx, Gilead, AbbVie, Scholar Rock, 1200 Pharma; Non-Financial Interests, Member of Board of Directors: Exigent Research Network. E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Novartis, Lilly, Pfizer, Mersana, iTeos, Janssen, Loxo, Relay Therapeutics, Olema Pharmaceuticals, Orum Therapeutics, Stemline Therapeutics, Arcus, AstraZeneca, Daiichi Sankyo, SeaGen, Ellipses Pharma, Greenwich LifeSciences, Tubulis, Verascity Science, Theratechnologies; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Millennium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Molecular Templates, Onconova Therapeutics, Dana Farber Cancer Hospital, Hutchinson MediPharma, MedImmune, SeaGen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, AbbVie, Nucana, Leap Therapeutics, Zenith Epigenetics, Harpoon, Orinove, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, PharmaMar, Olema, Immunogen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Atlas MedX, Ellipses, Incyte, Jacobio, Mabspace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Repertoire Immune Medicine, Treadwell Therapeutics, Accutar Biotechnology, Cascadian Therapeutics, Artios, BeiGene, Bliss BioPharmaceuticals, Context Therapeutics, Cullinan-Florentine, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Relay Therapeutics, Tolmar, Torque Therapeutics. A. Tazbirkova: Non-Financial Interests, Principal Investigator, Principal Investigator. Not remunerated.: Pindara Private Hospital. I.G. Sullivan: Financial Interests, Personal, Advisory Board: Roche, Novartis, Boehringer Ingelheim, Takeda, Sanofi, BMS; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Takeda, Pfizer, Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel grant: Roche, Takeda, Lilly, AstraZeneca. C. Van Marcke de Lummen: Financial Interests, Institutional, Advisory Board: Eli Lilly, Novartis, AstraZeneca; Non-Financial Interests, Member of Board of Directors: BSMO. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, CHUGAI, GSK; Financial Interests, Institutional, Coordinating PI: Bayer, AstraZeneca, Roche, MSD, IPSEN, MERCK. J. Patel: Financial Interests, Personal, Stocks/Shares: Gilead Sciences; Financial Interests, Personal, Full or part-time Employment: Gilead Sciences. S. Mekan: Financial Interests, Institutional, Full or part-time Employment: Gilead Sciences. T. Wu: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences; Financial Interests, Personal, Stocks/Shares: Gilead Sciences. A.C. Chiang: Financial Interests, Personal, Advisory Board, and consulting: AstraZeneca; Financial Interests, Personal, Advisory Board: Daichi, Genentech; Financial Interests, Institutional, Officer, SWOG Executive Officer for Lung and Breast: SWOG; Financial Interests, Institutional, Local PI: AstraZeneca, AbbVie, Genentech, BMS. All other authors have declared no conflicts of interest.