Trabectedin plus Durvalumab in Patients with Advanced Pretreated Soft Tissue Sarcoma and Ovarian Carcinoma (TRAMUNE): An Open-Label, Multicenter Phase Ib Study.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
02 05 2022
02 05 2022
Historique:
received:
20
06
2021
revised:
12
09
2021
accepted:
20
12
2021
pubmed:
31
12
2021
medline:
4
5
2022
entrez:
30
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34965951
pii: 1078-0432.CCR-21-2258
doi: 10.1158/1078-0432.CCR-21-2258
doi:
Substances chimiques
Antibodies, Monoclonal
0
durvalumab
28X28X9OKV
Trabectedin
ID0YZQ2TCP
Banques de données
ClinicalTrials.gov
['NCT03475953']
Types de publication
Research Support, Non-U.S. Gov't
Journal Article
Comment
Langues
eng
Sous-ensembles de citation
IM
Pagination
1765-1772Commentaires et corrections
Type : CommentIn
Type : CommentOn
Informations de copyright
©2021 American Association for Cancer Research.