Given the burden of comorbidities, lack of curative agents, and high mortality in pts with SCLC, novel treatment options with limited toxicity are needed. BMS-986012 is a first-in-class, fully human mAb with enhanced antibody-dependent cell-mediated cytotoxicity that binds to fucosyl-GM1, a ganglioside highly expressed on SCLC. BMS-986012 monotherapy is well tolerated and has shown evidence of antitumor activity in some pts with rel/ref SCLC in a phase 1/2 study (NCT02247349; Chu et al. Ann Oncol. 2016;27(6 suppl) [abstract 1427PD]). Here we present initial results of BMS-986012 + nivolumab (anti–programmed death-1 mAb) in pts with rel/ref SCLC (NCT02247349).
Pts with SCLC who relapsed after or were refractory to first-line therapy received BMS-986012 400 or 1000 mg + nivolumab 360 mg IV Q3W. Dose escalation was based on a modified toxicity probability interval design. Primary objectives were safety and tolerability and determination of dose-limiting toxicities (DLT) and maximum tolerated dose. Secondary objectives included pharmacokinetics, antitumor activity, and immunogenicity.
To date, 16 pts received BMS-986012 (400 mg, n = 8; 1000 mg, n = 8) + nivolumab. Demographic and safety data are based on 14 pts treated as of the April 3, 2017 cutoff. Median age was 64 y (range, 49-79 y), ECOG status was 0 (29%) or 1 (71%), and all pts were current (29%) or former (71%) smokers. All pts had prior platinum-based first-line therapy. The most common treatment-related AEs (TRAEs) were generalized pruritus (71%), vulvovaginal pruritus (21%), and dry skin (21%). Only 2 pts, both treated with 1000/360 mg, had G3/4 TRAEs (G3 pruritus with G4 lipase increase; G3 hepatic failure [DLT; led to discontinuation]). As of May 1, 2017, 4 of the 16 pts evaluable for efficacy achieved partial responses (2 unconfirmed). Updated efficacy data as well as data from ongoing biomarker analyses will be presented.
BMS-986012 in combination with nivolumab is well tolerated in pts with rel/ref SCLC, with no evidence of additive toxicity. Promising initial antitumor activity was observed with BMS-986012 + nivolumab in pts with rel/ref SCLC.
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Legal entity responsible for the study
N.B. Leighl: Research funding (institution) - Novartis. Travel/honoraria (unrelated CME) - AstraZenenca, Pfizer, Bristol-Myers Squibb, Merck, Sharpe & Dohme. R.A. Juergens: BMS: advisory board member, honoraria, and grant support; clinical trials funding to my institution (outside of submitted work). P. Basciano, S. Tannenbaum-Dvir, D. Williams, G. Kolaitis: BMS employee; Owner of BMS stock. D. Lathers, K. Urbanska: BMS employee; Ownership of BMS stock. G. Kollia: BMS employee owning company stock. C. Darby: Employee of Mindlance, Inc. and working at Bristol-Myers Squibb under contract. N. Ready: Personal fees from Bristol Myers Squibb, Merck, Celgene, AstraZeneca, and Abbvie outside of submitted work. All other authors have declared no conflicts of interest.