Xevinapant Combined with Pembrolizumab in Patients with Advanced, Pretreated, Colorectal and Pancreatic Cancer: Results of the Phase Ib/II CATRIPCA Trial.

Autor:	Voisin A; Molecular Regulation of Cancer Immunity, Cancer Research Center of Lyon, Labex DEV2CAN, Centre Léon Bérard, INSERM U1052, CNRS UMR5286, Université Claude Bernard Lyon 1, Lyon, France., Terret C; Department of Medical Oncology, Centre Léon Bérard, Lyon, France., Schiffler C; Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon, France., Bidaux AS; Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon, France., Vanacker H; Department of Medical Oncology, Centre Léon Bérard, Lyon, France., Perrin-Niquet M; Molecular Regulation of Cancer Immunity, Cancer Research Center of Lyon, Labex DEV2CAN, Centre Léon Bérard, INSERM U1052, CNRS UMR5286, Université Claude Bernard Lyon 1, Lyon, France., Barbery M; Molecular Regulation of Cancer Immunity, Cancer Research Center of Lyon, Labex DEV2CAN, Centre Léon Bérard, INSERM U1052, CNRS UMR5286, Université Claude Bernard Lyon 1, Lyon, France., Vinceneux A; Department of Medical Oncology, Centre Léon Bérard, Lyon, France., Eberst L; Department of Medical Oncology, Centre Léon Bérard, Lyon, France., Stéphan P; Molecular Regulation of Cancer Immunity, Cancer Research Center of Lyon, Labex DEV2CAN, Centre Léon Bérard, INSERM U1052, CNRS UMR5286, Université Claude Bernard Lyon 1, Lyon, France., Garin G; Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon, France., Spaggiari D; Debiopharm International SA, Lausanne, Switzerland., Pérol D; Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon, France., Grinberg-Bleyer Y; Molecular Regulation of Cancer Immunity, Cancer Research Center of Lyon, Labex DEV2CAN, Centre Léon Bérard, INSERM U1052, CNRS UMR5286, Université Claude Bernard Lyon 1, Lyon, France., Cassier PA; Molecular Regulation of Cancer Immunity, Cancer Research Center of Lyon, Labex DEV2CAN, Centre Léon Bérard, INSERM U1052, CNRS UMR5286, Université Claude Bernard Lyon 1, Lyon, France.; Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 May 15; Vol. 30 (10), pp. 2111-2120.
DOI:	10.1158/1078-0432.CCR-23-2893
Abstrakt:	Purpose: Xevinapant is an orally available inhibitor of apoptosis proteins (IAP) inhibitor. Preclinical data suggest that IAP antagonism may synergize with immune checkpoint blockers by modulating the NFκB pathway in immune cells. Patients and Methods: Adult patients with non-high microsatellite instability advanced/metastatic pancreatic ductal adenocarcinoma (PDAC) or colorectal cancer were enrolled in this phase Ib/II study and received pembrolizumab 200 mg every 3 weeks intravenously, and ascending doses of oral xevinapant (100, 150, and 200 mg daily for 14 days on/7 days off). Dose escalation followed a 3+3 design with a 21-day dose-limiting toxicity (DLT) evaluation period. Following the determination of the recommended phase II dose (RP2D), 14 patients with PDAC and 14 patients with colorectal cancer were enrolled in expansion cohorts to assess preliminary efficacy. Results: Forty-one patients (26 males) with a median age of 64 years were enrolled: 13 in the dose escalation and 28 in the two expansion cohorts. No DLT was observed during dose escalation. The RP2D was identified as xevinapant 200 mg/day + pembrolizumab 200 mg every 3 weeks. The most common adverse events (AE) were fatigue (37%), gastrointestinal AE (decreased appetite in 37%, nausea in 24%, stomatitis in 12%, and diarrhea and vomiting in 10% each), and cutaneous AE (pruritus, dry skin, and rash seen in 20%, 15%, and 15% of patients, respectively). The best overall response according to RECIST1.1 was partial response (confirmed) in 1 (3%), stable disease in 4 (10%), and progressive disease in 35 (88%). Conclusions: Xevinapant combined with pembrolizumab was well tolerated with no unexpected AEs. However, antitumor activity was low. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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