1528PD - Initial Results of BMS-986012, a First-in-Class Fucosyl-GM1 mAb, in Combination With Nivolumab, in Pts With Relapsed/Refractory (rel/ref) Small-Cel...

Date 11 September 2017
Event ESMO 2017 Congress
Session Non-metastatic NSCLC and other thoracic malignancies
Topics Small-Cell Lung Cancer
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter Quincy Siu-chung Chu
Citation Annals of Oncology (2017) 28 (suppl_5): v539-v542. 10.1093/annonc/mdx386
Authors Q.S. Chu1, C. van Herpen2, N.B. Leighl3, B. Markman4, S. Clarke5, R.A. Juergens6, P. Basciano7, D. Lathers7, S. Tannenbaum-Dvir7, K. Urbanska7, G. Kollia7, C. Darby7, D. Williams7, G. Kolaitis7, N. Ready8
  • 1Department Of Medical Oncology, Cross Cancer Institute, University of Alberta/Alberta Health Services, T6G 1Z2 - Edmonton/CA
  • 2Department Of Medical Oncology, Radboud University Medical Center Nijmegen, 6525 GA - Nijmegen/NL
  • 3Department Of Medical Oncology, Princess Margaret Cancer Centre, ON M5G1X6 - Toronto/CA
  • 4Department Of Oncology, Monash Health and Monash University, 3168 - Melbourne/AU
  • 5Department Of Medical Oncology, Royal North Shore Hospital, 2065 - St Leonards/AU
  • 6Department Of Medical Oncology, Juravinski Cancer Centre, L8V 5C2 - Hamilton/CA
  • 7Early Assets, Bristol-Myers Squibb, 08540 - Princeton/US
  • 8Department Of Medicine, Duke University Medical Center, NC 27710 - Durham/US

Abstract

Background

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).

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

NCT02247349

Legal entity responsible for the study

Bristol-Myers Squibb

Funding

Bristol-Myers Squibb

Disclosure

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.