Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2017

Initial efficacy of anti-lymphocyte activation gene-3 (anti–LAG-3; BMS-986016) in combination with nivolumab in patients with melanoma who progressed during prior anti–PD-1/PD-L1 therapy (#149)

Paulo A Ascierto 1 , Ignacio Melero 2 , Shailender Bhatia 3 , Petri Bono 4 , Rachel E Sanborn 5 , Evan J Lipson 6 , Margaret K Callahan 7 , Thomas Gajewski 8 , Carlos A Gomez-Roca 9 , F Stephen Hodi 10 , Giuseppe Curigliano 11 , Marta Nyakas 12 , Matthias Preusser 13 , Yoshinobu Koguchi 5 , Matthew Maurer 14 , Christopher Harbison 14 , Priyam Mitra 14 , Satyendra Suryawanshi 14 , Eva Munoz-Couselo 15 , Karl Hausler 16 , Jamie Lopez
  1. Istituto Nazionale Tumori Fondazione "G. Pascale", Napoli, Italy
  2. Clinica Universidad de Navarra, Pamplona, Spain
  3. University of Washington, Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
  4. Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland
  5. Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, United States
  6. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
  7. Memorial Sloan Kettering Cancer Center, New York, NY, United States
  8. University of Chicago Medical Center, Chicago, IL, United States
  9. Institut Universitaire du Cancer, Oncopole, Toulouse, France
  10. Dana-Farber Cancer Institute, Boston, MA, United States
  11. Istituto Europeo di Oncologia, Milano, Italy
  12. Oslo University Hospital, Oslo, Norway
  13. Medical University of Vienna, Comprehensive Cancer Center, Vienna, Austria
  14. Bristol-Myers Squibb, Princeton, NJ, United States
  15. Vall d´Hebron Institute of Oncology, Barcelona, Spain
  16. Bristol-Myers Squibb, Mulgrave, VIC, Australia


Simultaneous blockade of T-cell inhibitory receptors LAG-3 and PD-1 may synergistically restore T-cell activation and antitumor immunity, which is attenuated in many tumors, including melanoma. BMS-986016 (anti–LAG-3 monoclonal antibody [mAb]) ± nivolumab (anti–PD-1 mAb) demonstrated tolerability, peripheral T-cell activation, and preliminary clinical activity in a phase 1/2a study (NCT01968109; Lipson E, et al. J Immunother Cancer. 2016;4[s1]:173[P232]). Here we present preliminary efficacy of BMS-986016 + nivolumab in patients with melanoma who progressed during prior anti–PD-1/PD-L1 therapy (mel prior IO) and updated safety in all dose-expansion patients (n=212). 


Patients in the mel prior IO cohort received BMS-986016 80 mg + nivolumab 240 mg IV Q2W. Objectives included safety, objective response rate (ORR; complete [CR] + partial [PR] response), and disease control rate (DCR; CR + uCR + PR + uPR + stable disease [SD]).


As of April 7, 2017, 55 patients in the mel prior IO cohort received BMS-986016 + nivolumab. Fifty-two patients (95%) had prior anti–PD-1/PD-L1, 32 (58%) had prior anti–CTLA-4, 25 (45%) had ≥3 prior therapies, and 21 (38%) had BRAF mutations. Known prior best responses in the 52 patients with prior anti–PD-1/PD-L1 were 1 CR, 12 PR, 16 SD, and 22 progressive disease. In 48 efficacy-evaluable patients with prior anti–PD-1/PD-L1, ORR was 13% (confirmed/unconfirmed), and DCR was 54%, with benefit observed even in patients refractory to prior anti–PD-1. Median treatment duration in the 48 efficacy-evaluable patients was 14 weeks. ORR was higher in patients with LAG-3 expression ≥1% vs <1% (20% vs 7%). Any-grade and grade 3/4 treatment-related AEs occurred in 45% and 9%, respectively, across all 212 dose-expansion patients. 


BMS-986016 + nivolumab demonstrated encouraging initial efficacy in patients with melanoma who progressed during prior anti–PD-1/PD-L1 therapy, with a safety profile similar to nivolumab monotherapy.