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Supplementary Table from Trabectedin plus Durvalumab in Patients with Advanced Pretreated Soft Tissue Sarcoma and Ovarian Carcinoma (TRAMUNE): An Open-Label, Multicenter Phase Ib Study

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posted on 2023-03-31, 23:13 authored by Maud Toulmonde, Mehdi Brahmi, Antoine Giraud, Camille Chakiba, Alban Bessede, Michèle Kind, Emilie Toulza, Marina Pulido, Sabrina Albert, Jean-Philippe Guégan, Sophie Cousin, Simone Mathoulin-Pelissier, Raul Perret, Sabrina Croce, Jean-Yves Blay, Isabelle Ray-Coquard, Anne Floquet, Antoine Italiano
Supplementary Table from Trabectedin plus Durvalumab in Patients with Advanced Pretreated Soft Tissue Sarcoma and Ovarian Carcinoma (TRAMUNE): An Open-Label, Multicenter Phase Ib Study

Funding

PharmaMar

AstraZeneca

Institut Bergonié

PharmaMar and AstraZeneca

NetSARC+ (INCA & DGOS) LYRICAN

InterSARC

LabEx DEvweCAN

PIA Institut Convergence François Rabelais PLAsCAN

EURACAN

RHU4 DEPGYN

History

ARTICLE ABSTRACT

Trabectedin has shown preclinical synergy with immune checkpoint inhibitors in preclinical models. TRAMUNE is a phase Ib study investigating the combination of trabectedin with durvalumab through a dose escalation phase and two expansion cohorts, soft tissue sarcoma (STS) 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, 1,120 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. A total of 40 patients were included (dose escalation, n = 9; STS cohort, n = 16; ovarian carcinoma 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% confidence interval (CI), 0.2–33.9], and the 6-month PFR was 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 was 42.9% (95% CI, 17.7–71.1). Baseline levels of programmed death-ligand 1 expression and CD8-positive T-cell infiltrates were associated with PFS in patients with ovarian carcinoma. Combining trabectedin and durvalumab is manageable. Promising activity is observed in patients with platinum-refractory ovarian carcinoma.See related commentary by Digklia et al., p. 1745

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