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Trabectedin plus durvalumab manageable in STS

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Forty patients participated in this phase Ib investigational study and received a combination of trabectedin with durvalumab through a dose-escalation phase with 2 expansion cohorts (soft tissue sarcoma and ovarian carcinoma).

Trabectedin was given at 1 mg/m2, 1.2 mg/m2, and 1.5 mg/m2 on day 1, and in combination with durvalumab (1120 mg) on day 2, every 3 weeks.

Of the 40 participants, 9 were in the dose escalation phase, 16 in the soft tissue sarcoma cohort, and 15 in the ovarian cohort (80% platinum resistant/refractory).

The most frequent toxicities included grade 1-2 fatigue, nausea, neutropenia, and alanine/aspartate aminotransferase increase. A dose-limiting toxicity at 1.2 mg/m2 was experienced by 1 patient.  A dose of 1.2 mg/m2 was selected as the recommended phase II dose.

STS cohort results:
-Tumor shrinkage in 43% of patients
-Objective response rate of 7%
-Six-month progression-free rate of 28.6%

Ovarian carcinoma cohort results:
-Tumor shrinkage in 43% of patients
-Objective response rate of 21.4%
-Six-month progression-free rate of 42.9%

Baseline levels of PD-L1 expression and CD8-positive T-cell infiltrates were associated with progression-free survival in ovarian carcinoma patients.

Toulmonde M, Brahmi M, Giraud A, et al. Trabectedin plus durvalumab in patients with advanced pretreated soft tissue sarcoma and ovarian carcinoma (TRAMUNE): an open-label, multicenter phase Ib study. Clin Cancer Res. 2021;clincanres.2258.2021. doi: 10.1158/1078-0432.CCR-21-2258. Epub ahead of print. PMID: 34965951.