Abstract 1664TiP
Background
SCLC is an aggressive disease with limited treatment (tx) options. Pts with ES-SCLC have a poor prognosis with chemotherapy (5-y survival rate, 2%). The addition of approved checkpoint inhibitors to chemotherapy in the 1L have provided only modest benefit. Therefore, combination regimens with novel mechanisms of action are needed. Fucosyl-GM1 is a monosialoganglioside highly expressed on SCLC cells (50%-70% of tumors) but has limited expression in normal tissues. BMS-986012 is a nonfucosylated, first-in-class, fully human IgG1 monoclonal antibody that binds to fucosyl-GM1 with high affinity and specificity and was engineered to enhance antibody-dependent, cell-mediated cytotoxicity. We previously reported that BMS-986012 + platinum-etoposide was tolerable in tx-naive pts with ES-SCLC (Paz-Ares et al. WCLC 2020. Abstract 3416). BMS-986012 also demonstrated preliminary clinical activity and a manageable safety profile when combined with NIVO in pts with relapsed/refractory SCLC (Chu et al. WCLC 2020. Abstract 3396). Here we describe a phase II, randomized, open-label global study assessing the safety and efficacy of BMS-986012 combined with carboplatin-etoposide and NIVO as 1L therapy in pts with ES-SCLC (NCT04702880).
Trial design
Pts (≈ 120) aged ≥ 18 y with previously untreated ES-SCLC will be enrolled. Pts must have ≥ 1 measurable lesion per RECIST v1.1 and be eligible for platinum-based chemotherapy. Key exclusion criteria include any prior tx for 1L SCLC or symptomatic CNS metastases. Pts will be randomized 1: 1 to 4 cycles of induction with carboplatin-etoposide + NIVO ± BMS-986012 followed by NIVO ± BMS-986012 maintenance for ≤ 2 y. Primary endpoints are safety, tolerability, and progression-free survival as determined by blinded independent central review using RECIST v1.1. Secondary endpoints are additional efficacy parameters (including response rate, duration of response, and overall survival), tumor fucosyl-GM1 and PD-L1 expression and associations with antitumor activity, and BMS-986012 immunogenicity. The first pt was treated in March 2021.
Clinical trial identification
NCT04702880.
Editorial acknowledgement
Writing and editorial assistance was provided by Larra Yuelling, PhD, of Chrysalis Medical Communications, Inc., funded by Bristol Myers Squibb.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
Q. Chu: Financial Interests, Personal, Other, Consultancy and Honorarium: AbbVie; Financial Interests, Personal, Other, Consultancy and Honorarium: Amgen; Financial Interests, Personal, Other, Consultancy and Honorarium: Astellas; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Other, Consultancy and Honorarium: AstraZeneca; Financial Interests, Personal, Other, Consultancy and Honorarium: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Other, Consultancy and Honorarium: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Exactis; Financial Interests, Personal, Other, Consultancy and Honorarium: Eli Lilly; Financial Interests, Personal, Other, Consultancy and Honorarium: Merck; Financial Interests, Personal, Other, DSMB: Merck KGaA; Financial Interests, Personal, Other, Consultancy and Honorarium: Novartis; Financial Interests, Personal, Other, Consultancy and Honorarium: Pfizer; Financial Interests, Personal, Other, Consultancy and Honorarium: Roche; Financial Interests, Personal, Other, Consultancy and Honorarium: Takeda. K. Parikh: Financial Interests, Personal, Other, Consultancy: AstraZeneca; Financial Interests, Personal, Other, Consultancy: Beigene; Financial Interests, Personal, Other, Consultancy: Blueprint Medicine. L. Paz-Ares: Financial Interests, Personal, Leadership Role: Altum Sequencing; Financial Interests, Personal, Leadership Role: European Medicines Agency; Financial Interests, Personal, Leadership Role: Genomica; Financial Interests, Personal, Other, Honoraria: Advanced Accelerator Applications; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: Blueprint Medicines; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Celgene; Financial Interests, Personal, Other, Honoraria: Incyte; Financial Interests, Personal, Other, Honoraria: Ipsen; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Merck Serono; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: PharmaMar; Financial Interests, Personal, Other, Honoraria: Roche/Genentech; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Personal, Other, Honoraria: Servier; Financial Interests, Personal, Other, Honoraria: Sysmex; Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Funding: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel: AstraZeneca; Financial Interests, Personal, Other, Travel: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel: MSD; Financial Interests, Personal, Other, Travel: Pfizer; Financial Interests, Personal, Other, Travel: Roche; Financial Interests, Personal, Other, Travel: Takeda. A. Navarro: Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Expert Testimony: Oryzon Genomics; Financial Interests, Personal, Other, Travel: Boehringer Ingelheim; Financial Interests, Personal, Other, Travel: Pfizer; Financial Interests, Personal, Other, Travel: Roche. B. Markman: Financial Interests, Personal, Writing Engagements: Bristol Myers Squibb; Financial Interests, Personal, Writing Engagements: Merck; Financial Interests, Personal, Writing Engagements: Amgen; Financial Interests, Personal, Writing Engagements: Akeso Biopharma. R. Sarmiento: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. G. Kollia: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. C. He: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. K. Sanghavi: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. H. Chang: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. B. Fischer: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. U. Guha: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S. Tannenbaum-Dvir: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. K. Wu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. Y. Liu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. N. Ready: Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Writing Engagements: Bristol Myers Squibb; Financial Interests, Personal, Writing Engagements: G1; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Writing Engagements: Merck; Financial Interests, Personal, Writing Engagements: Regeneron; Financial Interests, Personal, Writing Engagements: AstraZeneca; Financial Interests, Personal, Writing Engagements: Genentech; Financial Interests, Personal, Writing Engagements: Roche; Financial Interests, Personal, Writing Engagements: Novartis; Financial Interests, Personal, Writing Engagements: Pfizer; Financial Interests, Personal, Writing Engagements: EMD Serono.