478P Metronomic oral vinorelbine (MOV) combined with tremelimumab (T) + durvalumab (D): Results of the tumor mutational burden-high (TMB-h) and/or microsatellite instability-high (MSI-h) cohort of the MOVIE study

Both TMB-h and MSI-h result in a high rate of neoantigens, which may favor the efficacy of immune checkpoint inhibitors. Pembrolizumab (an anti- PD1) has been FDA-approved in MSI-h/TMB-h advanced solid tumor (AST) with an agnostic indication. MOVIE is a multi-cohort phase I/II study examining the combination of T+D+MOV in AST. We report here the results of the TMB-h and/or MSI-h cohort in miscellaneous AST. Patients (pts) were eligible with TMB-h (as determined by a local molecular tumor board), and/or MSI-h (by locally performed PCR and IHC test). T was administered for up to 4 cycles (cy) and D for up to 26 cy (or 24 months (mo) whichever is longer). MOV was administered at 40 mg orally thrice weekly, until disease progression (PD). Primary endpoint of phase II part was clinical benefit rate (CBR= CR, PR or SD > 24 wks) according to RECIST 1.1. Continuous monitoring of efficacy was planned using a Bayesian approach, with a futility bound of 40%. Secondary objectives included safety, ORR, DOR, PFS and OS. 30 pts were included in the cohort: 10 MSI-h, 13 TMB-h and 7 both. Median age was 65 (35; 83). Median number of previous metastatic lines of systemic treatment was 1.5 (0 ; 10). As of April 2022, 9 pts were on treatment, 17 stopped for PD and 4 for unacceptable toxicity; median follow-up was 9.1 mo (1.4 – 24.1). Clinical benefit was observed for 15 pts: 1 CR, 9 PR, and 5 SD > 24 wks. Bayesian estimations of the mean CBR (95%(CI)) according to the prior distributions defined are reported in the table. 21 (70%) pts had grade ≥2 treatment-related adverse events, including 9 pts (30%) with grade ≥3. No toxic death was recorded. Bayesian estimations of the mean CBR.Table: 478PPrior non-informative beta (1,1)Informative Prior Beta (5.7,5.7)Less informative optimism Beta (1.3,1.3)Mean [95% CI]50% [33.1% ; 66.9%]50% [35.0% ; 65.0%]50% [33.2% ; 66.8%] Open table in a new tab T+D+MOV has promising activity in TMB-h and or MSI-h cohort. Toxicity profile was consistent with previous reports of T+D combination or MOV.