1925MO - Regomune study: A phase II study of regorafenib + avelumab in solid tumors. Results of the radioiodine-refractory differentiated thyroid cancer (RR-DTC)

Background

In refractory radioactive iodine-differentiated thyroid cancer (RR-DTC), anti-angiogenic agents like sorafenib, lenvatinib, and cabozantinib are key components of therapy. Combining these with immune checkpoint inhibitors could enhance therapeutic outcomes by targeting different mechanisms of tumor resistance and promoting a more robust anti-tumor immune response.

Methods

This phase II, single-arm, open-label, multicentric trial assessed the combination of regorafenib (160 mg daily for 3 weeks of a 4-week cycle) and avelumab (10 mg/kg biweekly) in RR-DTC patients. Primary endpoint was ORR by RECIST 1.1 after central review. Secondary endpoints included best overall response, 6-month ORR, progression-free survival (PFS), overall survival (OS), and safety. Correlative studies analyzed baseline tumor samples.

Results

From July 2019 to June 2023, 49 patients across 7 centers were enrolled, median age 67 (range: 37-83). Median follow-up was 10.5 months (95% CI: 8.6 – 22.1), with a median of 1 prior treatment line (range: 0-3). Twenty-five were TKI naive. Treatment modifications due to adverse events occurred in 41 (83.7%) patients. Common grade 3/4 adverse events included fatigue (22.4%), liver cytolysis (22.2%), and diarrhea (12.2%). No treatment-related deaths were reported. Among 44 evaluable patients, 25 (56.8%) achieved partial response, 14 (31.8%) had stable disease, and 5 (11.4%) progressed. ORR was 76% in TKI naive and 41.6% in previously treated patients. Median response duration was 13.1 months (95% CI: 7.4 – NR). Median PFS was 12.6 months (95% CI: 7.8 – 15.2); in TKI naive and previously treated patients, it was 12.6 and 20.4 months, respectively. Median OS has not been reached, with a one-year OS rate of 92% (95% CI: 71.1% – 98%). Biomarkers analysis will be reported at the meeting.

Conclusions

The Regomune study is the first to prospectively evaluate a combination of an immune checkpoint inhibitor with an anti-angiogenic agent in RR-DTC. The results demonstrate promising efficacy, particularly in patients previously treated with anti-angiogenics.

Clinical trial identification

NCT03475953.

Editorial acknowledgement

Legal entity responsible for the study

A. Italiano.

Funding

Bayer and Merck Serono S.A.S.

Disclosure

S. Cousin: Financial Interests, Personal, Advisory Board: Abbvie, Amgen, Lilly, Roche; Non-Financial Interests, Principal Investigator: AstraZeneca, Daiichi Sankyo, Gilead, Takeda, Sanofi, MSD, GSK, BMS. J. Hadoux: Financial Interests, Personal, Advisory Board: Ipsen, Lilly, PharmaMar; Financial Interests, Institutional, Invited Speaker: AAA, Pfizer, ITM; Financial Interests, Institutional, Advisory Board: Eisai, HRA pharma, Roche; Financial Interests, Institutional, Funding: Lilly. C.A. Gomez-Roca: Financial Interests, Personal, Invited Speaker: BMS, Roche / Genentech, Pierre Fabre; Financial Interests, Personal, Other, IDMC member: Pharmamar; Financial Interests, Personal, Advisory Board: Macomics, Ellipses Pharma, PSAD; Financial Interests, Institutional, Research Grant: Roche / Genentech, Amgen; Financial Interests, Institutional, Coordinating PI: Amunix, Kazia Therapeutics, IDEAYA; Non-Financial Interests, Member of Board of Directors: FITC (Société française d'Immuno-Thérapies du Cancer); Non-Financial Interests, Officer: ESMO Membership Committee, ESMO - MCBS Extended Working Group; Non-Financial Interests, Officer, Young Investigators Committee at imCORE: inFLAME; Non-Financial Interests, Member of Board of Directors, Network of Early Phase Units: OncoDistinct; Non-Financial Interests, Leadership Role: FITC (Société française d'Immuno-Thérapies du Cancer). 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, Bristol Meyer Squibbb, 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. S. Hescot: Financial Interests, Personal, Other, writing: Ipsen; Financial Interests, Personal, Advisory Board, board: MSD; Financial Interests, Institutional, Research Grant: Ipsen. I. Soubeyran: Financial Interests, Institutional, Invited Speaker, congress; meeting: AstraZeneca; Financial Interests, Institutional, Funding, research funding: AstraZeneca. 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.