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

Immune checkpoint inhibitor (ICI) effectiveness in unselected STS remains underwhelming but biological rationale suggest that MEK inhibitor combination may enhance response in advanced STS. 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). 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: 59MOMain efficacy outcomesEndpoint cohortPFR-16W, N Bayesian mean estimated success rate 95% credible interval (Prob. PFR-16W ≤30%)ORR, NPFS, weeks (95%CI)CG cohort, N= 25 Median age min-max: 59y 15-77 Median N prior lines: 4 1-72/25 10.7% 2.4% ; 24.3% (Prob=0.99)07.9 (7.0-8.0)SG cohort, N= 20 Median age: 66y 19–79 Median N prior lines: 2 1-85/20 26.1% 10.7% ; 45.4% (Prob=0.69)2/20 (2 PR)8.0 (7.4-16) Open table in a new tab 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.