Abstract 282P
Background
Anti-PD-1/PD-L1 blockade combined with chemotherapy is the first-line treatment for advanced biliary tract cancers (BTC). Combined anti-PD-1/CTLA-4 blockade using nivolumab (nivo) and ipilimumab (ipi) has shown encouraging activity in pts with intrahepatic cholangiocarcinoma (iCCA) and gallbladder carcinoma (GB) in two trials (CA209-538, SWOG1609). MoST-CIRCUIT (NCT04969887) further evaluates combined checkpoint blockade in this pt population.
Methods
60 pts with advanced iCCA or GB were enrolled across 14 Australian sites. Pts received nivo 3mg/kg and ipi 1mg/kg q3 weekly for 4 doses, followed by nivo 480mg q4 weekly for 96 weeks, or until disease progression or the development of unacceptable toxicity. Response (RECIST 1.1) was assessed every 12 weeks. Co-primary endpoints were objective response rate (ORR) and 6 month-progression free survival. Tumour genomic profiling was undertaken for 42 patients by NGS using the TSO500 or FoundationOne CDx assay.
Results
37 iCCA and 23 GB pts were enrolled with 47 (78%) being pre-treated with one line of therapy for metastatic disease including 12 with durvalumab. ORR was 15% in the overall population and 6% and 32% in iCCA and GB pts respectively, median duration of response was 4.2 months (range 1-10.4). The 6-month-PFS was 22.6% with the median OS being 6.7 months. Only one durvalumab pre-treated pt obtained a response. Tumours of all participants were microsatellite stable with a median TMB of 3.75/MB (range 0-12). TMB did not correlate with response (wilcox p=0.81) and analysis of genomic aberrations revealed two major clusters with GB being predominately part of a cluster characterised by TP53 mutations and CDKN2A deletions. 17 (28%) pts experienced a grade 3/4 immune –related adverse event.
Conclusions
Efficacy was limited in what is the largest BTC cohort treated to date with combined anti-CTLA-4/PD-1 blockade. However, encouraging activity was observed in GB pts, in keeping with recent findings identifying this BTC subtype as the most immune cell-rich. Only one pt who progressed on first-line chemo-immunotherapy with durvalumab responded to treatment. Further evaluation of immunotherapy using checkpoint blockade in BTC should focus on GB pts.
Clinical trial identification
NCT04969887.
Legal entity responsible for the study
Olivia Newton-John Cancer Research Institute.
Funding
Bristol Myers Squibb Ltd.; Omico; Minderoo Foundation; Medical Research Future Fund Australia.
Disclosure
M. Carlino: Financial Interests, Personal, Advisory Board, Consultant Advisor: MSD, BMS, Novartis, Amgen, Oncosec, Merck, Sanofi, Ideaya, Pierre Fabre, Eisai, Nektar, Regeneron. M. Brown: Financial Interests, Institutional, Advisory Board: BMS. C.R. Underhill: Financial Interests, Personal, Advisory Board: Merck Serono, AstraZeneca, Bayer. D. Kee: Financial Interests, Personal, Advisory Board: MSD, BMS, Medison. W. Lam: Financial Interests, Personal, Speaker’s Bureau: BMS. A. Nagrial: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, MSD. All other authors have declared no conflicts of interest.