1786O - BMS-986012 (anti-fucosyl-monosialoganglioside-1 [fuc-GM1]) with carboplatin + etoposide + nivolumab (CE/NIVO) as first-line (1L) therapy in extensive-stage small cell lung cancer (ES-SCLC): Interim analysis (IA) of a randomized phase II study

Background

BMS-986012, a first-in-class, fully human immunoglobulin G1, binds fuc-GM1 with high affinity and specificity, and induces immune-mediated tumor cell death. BMS-986012 has shown preliminary antitumor activity and tolerability with NIVO in SCLC, in which fuc-GM1 is often highly expressed. Here we report a prespecified IA from a phase II study of BMS-986012 + CE/NIVO (Arm A) vs CE/NIVO (Arm B) as 1L ES-SCLC treatment (Tx).

Methods

Eligible patients (pts) were randomized 1:1 to four 21-day cycles of CE/NIVO ± BMS-986012 induction Tx, followed by up to 2 years (y) of NIVO ± BMS-986012 maintenance Tx. Primary endpoints were safety and progression-free survival (PFS) by blinded independent central review; overall survival (OS) was a secondary endpoint. The study was stratified by liver metastasis and ECOG performance status (PS).

Results

As of Sep 26, 2023, 132 pts had been randomized. Arms (both n = 66) were balanced for baseline characteristics, with overall median (m) age of 67 y (range 41–80); 89% of pts were White and 8% Asian; 73% were in Europe and 12% in North America. Liver metastases were present in 42% of pts, and 25%/75% had ECOG PS 0/1. The safety profile was similar between arms (Table). PFS did not significantly differ between arms: mPFS was 5.8 months (mo) (95% confidence interval [CI] 5.0–7.9) in Arm A vs 5.2 mo (95% CI 4.8–6.6) in Arm B (hazard ratio [HR] 0.89 [95% CI 0.57–1.40]; P = 0.61). mOS was 15.6 mo (95% CI 11.3–NA) in Arm A (23 deaths) vs 11.4 mo (95% CI 9.3–16.5) in Arm B (30 deaths), HR 0.80 (95% CI 0.46–1.40). At a later database lock (Feb 26, 2024), mPFS was 5.8 mo vs 5.1 mo (HR 0.81 [95% CI 0.53–1.23]), and mOS was 15.6 mo vs 11.4 mo (HR 0.71 [95% CI 0.44–1.16]), in Arm A vs Arm B, respectively. Table: 1786O

*Grade 3 rash/grade 2 pruritus

Conclusions

BMS-986012 + CE/NIVO showed a tolerable safety profile as 1L ES-SCLC Tx, alongside a promising signal of improved OS vs CE/NIVO alone.

Clinical trial identification

NCT04702880.

Editorial acknowledgement

Writing and editorial assistance were provided by Gleb Baida, PhD, Rose Goodchild, PhD, and Tina Allen, BSc, of Spark (a division of Prime, New York, USA).

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

E. Kalinka: Financial Interests, Personal, Advisory Board, advisory board member, clinical trial and lectures honoraria: Bristol Myerrs Squibb; Financial Interests, Personal, Invited Speaker, lectures and clinical trials honoraria, advisory role: Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker, lectures honoraria, advisory role: GSK; Financial Interests, Personal, Invited Speaker, lectures and clinical trials honoraria: Roche; Financial Interests, Personal, Invited Speaker, lectures honoraria and writing engagement: Sanofi, Regeneron; Financial Interests, Personal, Advisory Board, advisory role, clinical trials and lectures honoraria: AstraZeneca; Financial Interests, Personal, Invited Speaker, advisory role, clinical trials and lectures honoraria: Gilead; Financial Interests, Personal, Invited Speaker, clinical trials and lectures honoraria: Amgen; Financial Interests, Personal, Ownership Interest: Institute MSF Sp zoo; Financial Interests, Personal and Institutional, Local PI: AstraZeneca, Roche, Bristol Myers Squibb, Gilead; Financial Interests, Personal, Local PI: Merck Sharp Dohme. I. Bahce: Financial Interests, Institutional, Advisory Board: BMS, Boehringer Ingelheim, AstraZeneca, Roche, Pfizer, Takeda, MSD; Financial Interests, Institutional, Research Grant: BMS, Boehringer Ingelheim, AstraZeneca. A.F. Navarro Mendivil: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Oryzon Genomics, Amgen, Hengenix Biotech, MedSIR, BMS; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Pfizer, Takeda, Tecnofarma; Non-Financial Interests, Principal Investigator: BMS, PharmaMar, MSD, Amgen, Novartis, Debiopharm, Daiichi Sankyo, Roche, AstraZeneca. N. Ready: Financial Interests, Personal, Other, Paid unbranded speaker: Jazz, Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Paid advisor: Regeneron, BMS, RAPT, Merck, AbbVie, Genentech, EMD Serono; Financial Interests, Personal, Advisory Board, Paid advisor: Pfizer. Q.S. Chu: Financial Interests, Personal, Advisory Board: Amgen, AnHeart, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, GSK, Jazz Pharmaceuticals, Janssen, Merck, Novartis, Pfizer, Roche, Takeda, AbbVie, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, AbbVie, Daiichi Sankyo; Financial Interests, Personal, Other, DSMB: EMD Sereno; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Local PI: Alkermes, Amgen, Apollomics, Arrivent Biopharma, Astellas, Bayer, Bicycle, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, AstraZeneca, Esperas, GSK, iTEO, Mirati, Nuvalent, Pfizer, Revolution Medicines, Roche, TreadWell, Arrivent, Conjupro, Ocellaris, Merck, Signal Chemo Biopharma; Financial Interests, Local PI: Beigene. S. Sugawara: Financial Interests, Personal, Other, Lecture fee: AstraZeneca, Chugai Pharma, Nippon Boehringer Ingelheim, Taiho Pharmaceutical, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Ono Pharmaceutical, MSD K.K, Kyowa Kirin, Takeda, Nippon Kayaku, Merck, Amgen, Thermo Fisher Scientific; Financial Interests, Personal, Other, Lecture Fee: Eisai, Sysmex; Financial Interests, Institutional, Local PI: AstraZeneca, Chugai Pharma, MSD K.K, Daiichi Sankyo, Bristol Myers Squibb, AnHeart, Ono Pharmaceutical, Nippon Boehringer Ingelheim, AbbVie, Parexel International, Amgen, Taiho Pharmaceutical, Accerise, A2 Healthcare, EPS Corporation, Syneos Health, PPD-SNBL. A. Sibille: Financial Interests, Institutional, Advisory Board: Merck Sharp Dome, AstraZeneca, Bristol Myers Squibb, Roche, Pfizer. M. Provencio Pulla: Financial Interests, Personal, Advisory Board: BMS, MSD, Bayer, Lilly, Roche, Takeda, Janssen; Financial Interests, Personal, Other, Consulting, support for attending meetings and/or travel, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: BMS, AstraZeneca, MSD, Roche, Takeda, Eli Lilly, F. Hoffman-La Roche, Janssen, Pzifer, Amgen, Boehringer Ingelheim, Pierre Fabre Pharmaceuticals; Financial Interests, Institutional, Coordinating PI: AstraZeneca, BMS, Takeda, MSD, Roche; Non-Financial Interests, Leadership Role, President of Spanish Lung cancer Group: President; Non-Financial Interests, Leadership Role, Instituto Investigación Sanitaria Puerta de Hierro: Director; Non-Financial Interests, Leadership Role, President: Grupo Oncológico para el Tratamiento de las Enfermedades Linfoides. M.L. Johnson: Financial Interests, Institutional, Other, Consulting: AbbVie, Amgen, Arcus Biosciences, Arrivent, AstraZeneca, Daiichi Sankyo, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Immunocore, Janssen, Jazz Pharmaceuticals, Merck, Mirati Therapeutics, Molecular Axiom, Novartis, Pyramid Biosciences, Alentis Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, D3 Bio Limitied, Fate Therapeutics, Gilead Sciences, Hookipa Biotech, Lilly, Normunity, Novocure, Pfizer, Revolution Medicines, Sanofi-Aventis, SeaGen, Synthekine, Takeda Pharmaceuticals, VBL Therapeutics; Financial Interests, Institutional, Research Grant: AbbVie, Adaptimmune, Amgen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Carisma Therapeutics, City of Hope National Medical Center, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchinson MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte, Janssen, Kartos Therapeutics, Loxo Oncology, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Syndax Pharmaceuticals, Takeda Pharmaceuticals, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, Vyriad, Y-mAbs Therapeutics, ArriVent BioPharma, Bayer, LockBody Therapeutics, Taiho Oncology, Conjupro, Immuneering Corporation, Impact Therapeutics, NextPoint Therapeutics, OncoC4, Summit Therapeutics, Systimmune, TheRas, Vividion. J.T.J.N. Hiltermann: Financial Interests, Institutional, Advisory Board: BMS, AZD, Roche, Boehringer Ingelheim Pfizer; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Roche; Non-Financial Interests, Principal Investigator: BMS, AstraZeneca, Roche, Novartis, Merck, GSK, Amgen, Gilead. T. Ciuleanu: Financial Interests, Institutional, Other, Principal Investigator: Jounce Therapeutics; Financial Interests, Personal, Other, speaker, consultancy, advisory board, principal investigator: Roche, Merck Sharp & Dohme, AstraZeneca, Pfizer, Bristol Myers Squibb, Eli Lilly, Amgen, Astellas, Novartis, Takeda; Financial Interests, Personal, Other, speaker, consultancy, advisory board: Janssen, Sandoz, Sanofi, Accord, Magna Pharm; Financial Interests, Personal, Other, Principal Investigator: Tesaro, Mirati, AbbVie, Celltrion; Financial Interests, Personal, Other, Principal Investigator: BeiGene. R. Dziadziuszko: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pfizer, Novartis, Takeda, MSD, Bristol Myers-Squibb, Bayer; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Coordinating PI: Roche, AstraZeneca; Financial Interests, Personal and Institutional, Local PI: MSD, Amgen, Celon Pharma, Pfizer, Novartis, Bristol Myers Squibb, Eli Lilly, Loxo; Financial Interests, Personal and Institutional, Other, Subinvestigator and ad hoc Consultant: PDC* line Pharma; Financial Interests, Local PI: OSE Immunotherapeutics; Non-Financial Interests, Institutional, Product Samples: Novartis, Pfizer, AstraZeneca, Roche. A. Santo: Financial Interests, Institutional, Sponsor/Funding: Bristol Myers Squibb. Y. Zhang: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb. Y. Liu: Financial Interests, Institutional, Full or part-time Employment: BMS; Financial Interests, Institutional, Stocks/Shares: BMS. R. Sarmiento: Financial Interests, Institutional, Full or part-time Employment, I am full time employee of BMS: BMS; Financial Interests, Institutional, Stocks/Shares, I own BMS shares: BMS. S. Tannenbaum-Dvir: Financial Interests, Institutional, Full or part-time Employment, Full time employee of BMS: BMS; Financial Interests, Personal, Stocks/Shares, I own stock in BMS: BMS. L. Ojalvo: Financial Interests, Personal, Full or part-time Employment, Full time employee in early clinical development: Bristol Myers Squibb. J. Wu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. K.J. O'Byrne: Financial Interests, Personal, Other, Advisor/consultant on project development by the company: TriStar; Financial Interests, Personal, Other, Invited speaker; advisory board: BMS; Financial Interests, Personal, Other, Advisory board; invited speaker: AstraZeneca, MSD, Janssen; Financial Interests, Personal, Other, advisory board; invited speaker: Roche; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Other, Advisory board: Pfizer; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board, Advice on development of Lasertinib: Yuhan; Financial Interests, Personal, Other, advisory board and invited speaker: Takeda, Seagen; Financial Interests, Personal, Advisory Board, Advice re cabozantinib: Ipsen; Financial Interests, Personal, Advisory Board, Advice of drug development program, advisory board work and invited speaker: Beigene; Financial Interests, Personal, Invited Speaker, Topic - Tepotinib: Merck; Financial Interests, Personal, Other, Sponsorship for travel, accommodation and registration for ESMO Congress, Paris, 2022: Bayer; Financial Interests, Personal, Other, Sponsorship to ESMO annual congress 2023 - flights, registration and accommodation: Sanofi; Financial Interests, Personal, Stocks/Shares, 5% non-dilutable shares in a start-up Pharma company: RepLuca Pharmaceuticals Pty Ltd; Financial Interests, Personal, Stocks/Shares, Start-up diagnostics focused on genomics: DGC diagnostics; Financial Interests, Personal, Other, Co-founder, board member and share holder (15%) in the Pharma and biotech company: Carpe Vitae Pharmaceuticals Pty Ltd; Financial Interests, Personal, Steering Committee Member, Steering committee member 2 trials- CA-209-227- CA-001-050: BMS; Financial Interests, Personal, Steering Committee Member, Steering Committee member LUX-Lung program: Boehringer Ingelheim; Non-Financial Interests, Other, Chair an education session: foundation medicine.