PURPOSE: Trabectedin has shown pre-clinical synergy with immune-checkpoint inhibitors in pre-clinical models. EXPERIMENTAL DESIGN: TRAMUNE is a phase Ib study investigating trabectedin combined with durvalumab trough a dose-escalation phase and two expansion cohorts (soft tissue sarcoma and ovarian carcinoma). Trabectedin was given at three dose levels (1 mg/m2, 1.2 mg/m2 and 1.5 mg/m2) on day 1, in combination with durvalumab, 1120 mg on day 2, every 3 weeks. The primary endpoints were the recommended phase II dose (RP2D) of trabectedin combined with durvalumab and the objective response rate (ORR) as per RECIST 1.1. The secondary endpoints included safety, 6-month progression-free rate (PFR), progression-free survival (PFS), overall survival, and biomarker analyses. RESULTS: 40 patients were included (dose escalation: n=9; STS cohort: n=16; ovarian cohort: n=15, 80% platinum resistant/refractory). The most frequent toxicities were grade 1-2 fatigue, nausea, neutropenia, and alanine/aspartate aminotransferase increase. One patient experienced a dose-limiting toxicity at dose level 2. Trabectedin at 1.2 mg/m2 was selected as the RP2D. In the STS cohort, 43% of patients experienced tumor shrinkage, the ORR was 7% (95% CI 0.2 - 33.9) and the 6-month PFR 28.6% (95% CI 8.4-58.1). In the ovarian carcinoma cohort, 43% of patients experienced tumor shrinkage, the ORR was 21.4% (95% CI 4.7 - 50.8) and the 6-month PFR 42.9% (95% CI 17.7 - 71.1). Baseline levels of PD-L1 expression and CD8-positive T-cell infiltrates were associated with PFS in ovarian carcinoma patients. CONCLUSIONS: Combining trabectedin and durvalumab is manageable. Promising activity is observed in platinum-refractory ovarian carcinoma patients.< Réduire