820P Nivolumab (NIVO) +/- relatlimab (RELA) or ipilimumab (IPI) for patients (pts) with advanced treatment-naïve or -refractory basal cell carcinoma (BCC)

Standard therapies for pts with locally-advanced or metastatic BCC (aBCC) include hedgehog pathway inhibitors (HHi), limited by tolerability, and 2nd-line (2L) anti-PD-1, limited by suboptimal response rates (∼20-30%). 1L anti-PD-1 efficacy data are limited to case reports, and anti-LAG-3 data have not been reported in BCC. The current study tests NIVO (anti-PD-1) alone in treatment-naïve and HHi-experienced pts, and NIVO+RELA (anti-LAG-3) or NIVO+IPI (anti-CTLA-4) in anti-PD-1-refractory aBCC (NCT03521830). The primary endpoint was overall response rate (ORR) per RECIST v1.1. Treatment-naïve and HHi-experienced pts with aBCC received NIVO 480 mg IV q4 weeks (W) for ≤48W. Pts with stable disease (SD) at ≥36W or progressive disease (PD) on anti-PD-1 received NIVO 480 mg + RELA 480 or 960 mg IV q4W x 12, or NIVO 240 mg + IPI 1 mg/kg IV q3W x 4 then NIVO 480mg q4W x 7. H&E-stained tumor biopsy specimens taken 2-12W after treatment initiation or regimen change were scored for % residual viable tumor (RVT) [Stein, et al. Ann Oncol, 2019]. 24 pts (5 metastatic) were enrolled 12/2018 – 3/2022, 22 of whom were evaluable. Pts received NIVO (n=15; 10 treatment-naïve), NIVO+RELA (n=8), or NIVO+IPI (n=1). Median follow-up was 9.9 mo (range 1.8 - 38.4). Toxicities associated with each regimen were consistent with previous experience. Complete or partial response (CR, PR) to NIVO was observed in 5/10 (50%) and 1/5 (20%) pts in the 1L and 2L settings, respectively. 9 pts had SD (median duration 8 mo). 6 evaluable pts received NIVO+RELA; PD (n=1), SD (n=4), PR (n=1, 0% RVT at 4W; this pt had SD >48W on 1L NIVO). One pt who received NIVO+IPI after HHi and NIVO had PD. No responses were seen in 5 pts with metastatic BCC regardless of cohort. In 14/15 pts who received NIVO or NIVO+RELA and underwent tumor biopsy at ≤12W, ≤35% RVT was associated with PR or CR. 1L NIVO demonstrated an ORR of 50% among 10 pts with aBCC. NIVO+RELA mediated tumor regression in 1/6 anti-PD-1-refractory pts. ≤35% RVT in on-treatment biopsy was associated with response and warrants further exploration as a predictive biomarker. These preliminary findings in this ongoing trial support testing NIVO+RELA in treatment-naïve pts with aBCC.