44P - Chemo-immunotherapy combination of mFOLFOX6, bevacizumab and atezolizumab after first-line therapy for advanced biliary tract cancer: The COMBATBIL imCORE trial

Background

Standard 1st line treatment for advanced biliary tract cancer (BTC) involves GemCis and PD1/PDL1 inhibitors supported by TOPAZ-1 and KEYNOTE-966 trials. The ABC-06 trial showed a modest benefit of mFOLFOX6 in 2nd line therapy. Our phase 1b/2 study, COMBATBIL (NCT05052099), explored combined angiogenic and immune targeting with chemo by evaluating the efficacy and safety of mFOLFOX6 with bevacizumab and atezolizumab in PD1/PDL1 naïve patients (pts) after progression to 1st line therapy.

Methods

Eligible pts with unresectable/metastatic disease and ≥ 1 prior therapy, measurable disease per RECIST v1.1, and ECOG ≤ 1 received mFOLFOX6, atezolizumab 840 mg and bevacizumab 10 mg/kg IV biweekly until disease progression, unacceptable toxicity, or voluntary withdrawal. Primary endpoint overall response rate (ORR) by RECIST v1.1. Secondary endpoints: disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), ORR by independent radiological review, overall survival (OS), and safety assessed by CTCAE v5.0. Ongoing exploratory analyses include tumor biopsies (genomic alterations, biomarker expression), blood (immuno-phenotyping), and fecal samples (microbiome analysis).

Results

Recruitment completed with 35 pts as of September 12, 2023 and the data cut-off for analysis was April 30, 2024. Median age was 61 (range 30-78), with 18 males and 17 females. ORR was 31.4% (1 CR, 10 PR of 35 pts). DCR was 77.1%. DoR was 6.9 mo (95%CI 2.8-9.4). Median PFS was 8.36 mo (95%CI 5.49-10.69) and median OS was 13.8 mo (95%CI 11.7-17.5). Treatment for 3 pts was still ongoing at data cut-off. No new safety signals were observed. Adverse events of special interest (AESI) were observed in 8% of pts (3/35), 1 grade ≥3. 24.3% experienced AE leading to study drug discontinuation. Ongoing translational studies will be presented at the meeting.

Conclusions

mFOLFOX6, bevacizumab and atezolizumab showed a clinically meaningful ORR of 31% and superior OS in advanced BTC patients who progressed after 1^st line therapy when compared to OS benchmarks from the ABC-06 trial. Further randomized data is warranted to confirm these findings and support the use of this combination in clinical practice.

Clinical trial identification

EudraCT 2018-000257-45; NCT05052099.

Editorial acknowledgement

Legal entity responsible for the study

West German Cancer Center, University Hospital Essen, University Duisburg-Essen.

Funding

Roche through the imCORE network.

Disclosure

M. Ponz-Sarvise: Financial Interests, Personal, Advisory Board: Taiho, AstraZeneca; Financial Interests, Institutional, Funding: Roche, Novocure; Financial Interests, Institutional, Coordinating PI: AstraZeneca; Non-Financial Interests, Other, imFLAME Committee member: Roche. A. Landa Magdalena: Financial Interests, Personal, Other, Educational and travel support: Pfizer, Roche, Merck, Sanofi, Rovi, PharmaMar, AstraZeneca, Incyte. S. Kasper-Virchow: Financial Interests, Personal, Invited Speaker: BMS, MSD, Lilly, Merck, Amgen, Servier, Daiichi Sankyo, Pierre Fabre; Financial Interests, Personal, Advisory Board: GSK, Novartis, AstraZeneca; Financial Interests, Personal, Research Grant, IMAGINE Trial: BMS; Financial Interests, Personal, Coordinating PI, PIONEER and ANTONIO: Roche; Financial Interests, Personal, Coordinating PI, RAMTAS: Lilly; Non-Financial Interests, Advisory Role: BMS, MSD, Amgen, Merck, Lilly, Servier, AstraZeneca; Non-Financial Interests, Member: ASCO, DGHO. R. Garonce-Hediger: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche. E. Castanon Alvarez: Financial Interests, Personal, Advisory Board: MSD, Roche, BMS, Pfizer; Financial Interests, Personal, Invited Speaker: GSK; Non-Financial Interests, Principal Investigator: AZ, BMS, Roche, MSD, GSK, ARC, Ascendis, Sanofi. J.T. Siveke: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Servier, Immunocore, PSL Group, Novartis, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Roche, MSD Sharp & Dohme, MCI Deutschland, Falk Foundation; Financial Interests, Personal, Stocks/Shares: FAPi Holding AG; Financial Interests, Institutional, Coordinating PI, Trial support: AstraZeneca, Bristol Myers Squibb, Roche/Genentech; Financial Interests, Institutional, Research Grant, Project support: Abalos Therapeutics, Boehringer Ingelheim, Eisbach Bio GmbH. All other authors have declared no conflicts of interest.