Trabectedin plus durvalumab in patients with advanced pretreated soft tissue sarcoma and ovarian carcinoma (TRAMUNE): an open-label, multicenter phase Ib study
| dc.rights.license | open | en_US |
| dc.contributor.author | TOULMONDE, Maud | |
| dc.contributor.author | BRAHMI, Mehdi | |
| dc.contributor.author | GIRAUD, Antoine | |
| dc.contributor.author | CHAKIBA, Camille | |
| dc.contributor.author | BESSEDE, Alban | |
| dc.contributor.author | KIND, Michele | |
| dc.contributor.author | TOULZA, Emilie | |
| dc.contributor.author | PULIDO, Marina | |
| dc.contributor.author | ALBERT, Sabrina | |
| dc.contributor.author | GUEGAN, Jean Philippe | |
| dc.contributor.author | COUSIN, Sophie | |
| hal.structure.identifier | Bordeaux population health [BPH] | |
| dc.contributor.author | MATHOULIN-PELISSIER, Simone | |
| dc.contributor.author | PERRET, Raul | |
| dc.contributor.author | CROCE, Sabrina | |
| dc.contributor.author | BLAY, Jean Yves | |
| dc.contributor.author | RAY-COQUARD, Isabelle | |
| dc.contributor.author | FLOQUET, Anne | |
| dc.contributor.author | ITALIANO, Antoine | |
| dc.date.accessioned | 2022-01-24T10:28:02Z | |
| dc.date.available | 2022-01-24T10:28:02Z | |
| dc.date.issued | 2021-12-29 | |
| dc.identifier.issn | 1557-3265 (Electronic) 1078-0432 (Linking) | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/124601 | |
| dc.description.abstractEn | 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. | |
| dc.language.iso | EN | en_US |
| dc.title.en | Trabectedin plus durvalumab in patients with advanced pretreated soft tissue sarcoma and ovarian carcinoma (TRAMUNE): an open-label, multicenter phase Ib study | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1158/1078-0432.CCR-21-2258 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Santé publique et épidémiologie | en_US |
| dc.identifier.pubmed | 34965951 | en_US |
| bordeaux.journal | Clinical Cancer Research | en_US |
| bordeaux.hal.laboratories | Bordeaux Population Health Research Center (BPH) - UMR 1219 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | INSERM | en_US |
| bordeaux.team | EPICENE_BPH | |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| hal.identifier | hal-03540805 | |
| hal.version | 1 | |
| hal.date.transferred | 2022-01-24T10:28:06Z | |
| hal.export | true | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Clinical%20Cancer%20Research&rft.date=2021-12-29&rft.eissn=1557-3265%20(Electronic)%201078-0432%20(Linking)&rft.issn=1557-3265%20(Electronic)%201078-0432%20(Linking)&rft.au=TOULMONDE,%20Maud&BRAHMI,%20Mehdi&GIRAUD,%20Antoine&CHAKIBA,%20Camille&BESSEDE,%20Alban&rft.genre=article |
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