Multicenter Phase I/II Trial of Napabucasin and Pembrolizumab in Patients with Metastatic Colorectal Cancer (EPOC1503/SCOOP Trial)

医学 彭布罗利珠单抗 队列 内科学 结直肠癌 不利影响 肿瘤科 临床终点 临床试验 癌症 胃肠病学 免疫疗法
作者
Akihito Kawazoe,Yasutoshi Kuboki,Eiji Shinozaki,Hiroki Hara,Tomohiro Nishina,Yoshito Komatsu,Satoshi Yuki,Masashi Wakabayashi,Shogo Nomura,Akihiro Sato,Takeshi Kuwata,Masahito Kawazu,Hiroyuki Mano,Yosuke Togashi,Hiroyoshi Nishikawa,Takayuki Yoshino
出处
期刊:Clinical Cancer Research [American Association for Cancer Research]
卷期号:26 (22): 5887-5894 被引量:64
标识
DOI:10.1158/1078-0432.ccr-20-1803
摘要

This is a phase I/II trial to assess the efficacy and safety of napabucasin plus pembrolizumab for metastatic colorectal cancer (mCRC).Phase I was conducted to determine the recommended phase 2 dose (RP2D) in a dose escalation design of napabucasin (240 to 480 mg twice daily) with 200 mg pembrolizumab every 3 weeks. Phase II included cohort A (n = 10, microsatellite instability high, MSI-H) and cohort B (n = 40, microsatellite stable, MSS). The primary endpoint was immune-related objective response rate (irORR). PD-L1 combined positive score (CPS), genomic profiles, and the consensus molecular subtypes (CMS) of colorectal cancer were assessed.A total of 55 patients were enrolled in this study. In phase I, no patients experienced dose-limiting toxicities, and napabucasin 480 mg was determined as RP2D. The irORR was 50.0% in cohort A and 10.0% in cohort B. In cohort B, the irORR was 0%, 5.3%, and 42.9% in CPS < 1, 1≤ CPS <10, and CPS ≥ 10, respectively. Patients with objective response tended to have higher tumor mutation burden than those without. Of evaluable 18 patients for CMS classification in cohort B, the irORR was 33.3%, 0%, 33.3%, and 33.3% in CMS1, CMS2, CMS3, and CMS4, respectively. The common grade 3 or higher treatment-related adverse events included fever (10.0%) in cohort A and decreased appetite (7.5%) and diarrhea (5.0%) in cohort B.Napabucasin with pembrolizumab showed antitumor activity with acceptable toxicities for patients with MSS mCRC as well as MSI-H mCRC, although it did not meet the primary end point. The impact of related biomarkers on the efficacy warrants further investigations in the additional cohort.See related commentary by Nusrat, p. 5775.
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