1920MO - Regomune: A phase II study of regorafenib + avelumab in solid tumors - Results of the advanced or metastatic gastrointestinal stromal tumors (mGIST) cohort

Background

Regorafenib (R) has been approved as 3d line in mGIST patients (pts), with a median progression-free survival (mPFS) of 4.9 months (GRID study). R can alleviate the immunosuppressive GIST tumor micro environment by several mechanisms such as modifying the polarization of tumor-associated macrophages, reducing T regs infiltration. Thus, combining anti-PD1/PDL1 agents with anti-angiogenics appears promising in this population.

Methods

This is a single-arm open-label multicentric phase II trial assessing the efficacy and safety of R (160 mg QD 3weeks/4) + Avelumab (A) (10 mg/kg every 2 weeks) combination in pts with mGIST. The primary endpoint was the 6-month progression-free rate (6-month PFR) based on RECIST 1.1 criteria after central review. Secondary endpoints included: 6-month objective response, 1-year PFS, 1-year overall survival (OS), and safety using NCI-CTCAE v5.0. Correlative studies were planned from pts tumor samples obtained at baseline.

Results

Between November 2018 to July 2022, 50 pts were enrolled in 6 centers. Median age was 64 (range: 26-82). Median follow-up was 28.6 months (95% CI: 15.5 – 35.2). Median number of previous treatment lines was: 2 (range: 1-4). 42 (84%) pts experienced at least 1 dose modification or treatment interruption due to R and/or A. The most common grade 3/4 adverse events were: Palma-plantar erythrodysesthesia syndrome (18% of pts), hypertension (14%), diarrhea and maculopapular rash (12% each). No death was related to the treatment. Among the 46 assessable pts, 6-month PFR is 37% (N=17): 3 (6.5%) had partial response, 14 (30.4%) a stable disease, 23 (50%) a progressive disease, 6 were not evaluable. 24 (52.2%) had tumor shrinkage. Median PFS and OS are 5.5 months (95% CI: 3.6 – 7.5) and 19.5 months (95% CI: 13.7-33.5) respectively. 22% of pts are progression-free at one year. 6-month and 1-year OS rates are 93.5% (95% CI: 81.1-97.8) and 70.8% (95%CI: 55-81.9) respectively.

Conclusions

Regomune is the largest prospective study evaluating an approved TKI in combination with an IO agent in pts with advanced GIST. A subset of pts derived long term clinical benefit. Correlative studies will be presented at the meeting.

Clinical trial identification

NCT03475953.

Editorial acknowledgement

Legal entity responsible for the study

S. Cousin.

Funding

Bayer and Merck Serono S.A.S.

Disclosure

S. Cousin: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, BMS, MSD, Novartis; Financial Interests, Personal, Advisory Board: Sanofi, AbbVie; Non-Financial Interests, Institutional, Principal Investigator: MSD, BMS, GSK, Sanofi, AbbVie, Roche. T. Valentin: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, GSK, Blueprint. B. Verret: Financial Interests, Personal, Other, travel expenses: Lilly, Novartis, Pfizer, accord healthcare, Amgen, AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Speaker, Consultant, Advisor: Lilly, Daiichi Sankyo, Novartis, MSD, AstraZeneca, Owkins; Financial Interests, Personal, Speaker, Consultant, Advisor: Pfizer, Netcancer, Pierre Fabre, Seagen, Gilead. A. Adenis: Financial Interests, Personal, Advisory Board: Bayer, BMS, MSD; Financial Interests, Personal, Invited Speaker: Novartis, BMS; Financial Interests, Personal, Other, Travel: Servier, BMS, MSD; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Coordinating PI: Roche, BMS, MSD, Sanofi; Financial Interests, Institutional, Local PI: BeiGene, AstraZeneca. P. Cassier: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Roche, Amgen, Boehringer Ingelheim; Financial Interests, Personal, Other, Advisor: OSE immunotherapeutics; Financial Interests, Institutional, Local PI: AbbVie, Blueprint, Boehringer Ingelheim, BMS, Exelixis, GSK, Incyte, Janssen, Loxo/Eli Lilly, Novartis, Roche, Taiho, Toray Industries; Financial Interests, Institutional, Coordinating PI: Amgen, Transgene; Non-Financial Interests, Institutional, Product Samples: Plexxikon, Novartis, MSD, AstraZeneca, GSK. A. Hollebecque: Financial Interests, Personal, Invited Speaker: Servier, Incyte, Eisai; Financial Interests, Personal, Advisory Board: Basilea, Taiho, Relay Theraeutics, QED Therapeutics, Debiopharm, MSD, Boehringer Ingelheim; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Principal Investigator, M19-345: AbbVie; Non-Financial Interests, Principal Investigator, CO42216; WP42627; CO40939: Roche; Non-Financial Interests, Principal Investigator, MCLA-158: Merus; Non-Financial Interests, Principal Investigator, SGNB6A: Seatle Genetics; Non-Financial Interests, Principal Investigator, TAS-120-202: Taiho; Non-Financial Interests, Principal Investigator, Krystal-10: Mirati; Non-Financial Interests, Principal Investigator, ADP-0033: Adaptimmune; Non-Financial Interests, Principal Investigator, ACT16902: Sanofi; Non-Financial Interests, Principal Investigator, C4201002: Pfizer; Non-Financial Interests, Principal Investigator, RLY-4008: Relay Therapeutics; Non-Financial Interests, Principal Investigator, CC-90011: Celgene/BMS; Non-Financial Interests, Principal Investigator, Loxo-IDH: Loxo/Lilly; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator, SN-201 study: Sotio; Non-Financial Interests, Principal Investigator, Tropics-03: Gilead; Non-Financial Interests, Principal Investigator, BI1403: Boehringer Ingelheim. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Coordinating PI: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. All other authors have declared no conflicts of interest.