59MO - COTESARC – A multicentre, phase I-II clinical trial evaluating the combination of MEK and PDL-1 inhibitors in patients (pts) with advanced soft tissue sarcoma (STS): Results from complex (CG) and simple genomic (SG) STS cohorts

Background

Immune checkpoint inhibitor (ICI) effectiveness in unselected STS remains underwhelming but biological rationale suggest that MEK inhibitor combination may enhance response in advanced STS.

Methods

COTESARC is a multicenter, open-label, phase I-II trial evaluating cobimetinib (60 mg orally once daily for days 1 – 21 over 28 days-cycle) plus atezolizumab (840 mg intravenously every 2 weeks) in CG STS, SG STS, malignant peripheral nerve sheath tumors (MPNST), and rhabdomyosarcoma (RMS) cohorts. The progression-free-rate at 16 weeks (PFR-16W) is analysed sequentially every 10 pts per cohort according to a Bayesian approach. The enrolment could be stopped in case of probability for the PFR-16w to be ≤ 30%. Key secondary endpoints are safety, overall response rate (ORR) and progression-free survival (PFS).

Results

Baseline characteristics and main efficacy outcomes are presented for CG and SG cohorts in the table. Unexpected grade 3 myocarditis incidence (n=3/20) was reported. Efficacy outcomes are detailed in the table. With a median follow-up of 18.6 months, 3 pts are still under study treatment: 1 undifferentiated pleomorphic sarcoma and 2 SG STS including 1 alveolar soft part sarcoma with impressive response leading to surgical complete resection.

Table: 59MO

Main efficacy outcomes

Conclusions

Cobimetinib + atezolizumab not seems to demonstrate synergic clinical activity and is associated with an unexpected incidence of myocarditis. Yet, some patients benefit from the combination with long lasting response. Enrollment in MPNST and RMS cohorts is ongoing.

Clinical trial identification

NCT04216953.

Editorial acknowledgement

Legal entity responsible for the study

Centre Léon Bérard.

Funding

Roche.

Disclosure

A. Dufresne: Non-Financial Interests, Personal, Project ssLead, Translational research project: GSK, Adaptimmune; Non-Financial Interests, Personal, Project Lead, Translational research program: Bayer. M. Brahmi: Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Amgen, PharmaMar, Deciphera. P. Pautier: Financial Interests, Personal, Advisory Board, 2015, 2022: PharmaMar; Financial Interests, Institutional, Advisory Board, 2020: Roche, Clovis; Financial Interests, Institutional, Advisory Board, 2021: AstraZeneca; Financial Interests, Personal, Advisory Board, 2019-2020: AstraZeneca; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Personal, Advisory Board, 2018-2019: Roche; Financial Interests, Institutional, Expert Testimony, 2022: MSD; Financial Interests, Personal and Institutional, Research Grant: PharmaMar; Financial Interests, Personal, Research Grant: ONXEO. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmune, Eisai, SUTRO, BMS, Adaptimmune, Daiichi Sankyo; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Personal, Principal Investigator: PAOLA1; Non-Financial Interests, Personal, Other, President: GINECO. J-Y. Blay: Financial Interests, Institutional, Invited Speaker: MSD, MSD, PharmaMar; Financial Interests, Institutional, Advisory Board: Bayer, GSK, Roche; Financial Interests, Personal, Advisory Board: Deciphera; Financial Interests, Personal, Other, member of the supervisory board. No remunerations in 2021 and 2022.: Innate pharma; Financial Interests, Personal, Member of Board of Directors: Transgene; Financial Interests, Institutional, Funding: MSD, BMS, Deciphera; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bayer, GSK, Novartis, OSE pharma. All other authors have declared no conflicts of interest.