Abstract 820P
Background
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).
Methods
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].
Results
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.
Conclusions
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.
Clinical trial identification
NCT03521830.
Editorial acknowledgement
Legal entity responsible for the study
Principal Investigator: E.J. Lipson, M.D, Johns Hopkins University.
Funding
Bristol Myers Squibb (Hopkins BMS Immuno-Oncology Collaborative); The Bloomberg∼Kimmel Institute for Cancer Immunotherapy; The Marilyn and Michael Glosserman Fund for Basal Cell Carcinoma and Melanoma Research; The John P. Hussman Foundation.
Disclosure
J.S. Deutsch: Financial Interests, Personal, Other, Application No: 63/313,548: Patent pending. W.H. Sharfman: Financial Interests, Personal, Invited Speaker, non-branded speaker series consultant and speaker: BMS; Financial Interests, Personal, Other, Leads discussion groups on melanoma therapy: Merck; Financial Interests, Personal, Advisory Board: Regeneron, Pfizer, AmerisourceBergen; Financial Interests, Institutional, Invited Speaker: BMS, Merck, Genentech, AstraZeneca, Novartis. P.N. Brothers: Financial Interests, Personal, Invited Speaker, Non-branded education side effect management, care coordination multidisciplinary teams, mechanism of action immune-modulating therapies, ICI FDA-approved Cancer treatments for specific cancers: Merck. K. Bibee: Financial Interests, Personal, Advisory Role, consultant: Sanofi. J.M. Taube: Financial Interests, Personal, Stocks/Shares: Akoya Biosciences; Financial Interests, Personal, Advisory Role, consulting: Akoya Biosciences, BMS, Merck, AstraZeneca; Financial Interests, Personal, Funding, + equipment loan/reagent provision: Akoya Biosciences; Financial Interests, Personal, Funding: BMS; Financial Interests, Personal, Royalties, patent: multiplex IF image analysis; Financial Interests, Personal, Advisory Board, consultant: Genentech; Financial Interests, Personal, Advisory Role, consultant: Lunaphone, Compugen; Financial Interests, Personal, Licensing Fees, licensing of process to handle multiplex images using Astropath platform: Astropath platform. S.L. Topalian: Financial Interests, Personal, Advisory Role, consulting: AstraZeneca, Immunocore; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares, also consulting: Dragonfly Therapeutics, Five Prime Therapeutics. E.J. Lipson: Financial Interests, Personal, Advisory Board: Bristol Myers-Squibb, Merck, Sanofi, Regeneron, Genentech, Odonate Therapeutics, Eisai, Instil Bio, Natera, Nektar Therapeutics, OncoSec, Pfizer, Rain Therapeutics; Financial Interests, Personal, Other, Consultant: Macrogenics; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Regeneron, Merck. All other authors have declared no conflicts of interest.