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.