RT Journal Article
SR Electronic
T1 Multicenter Phase I/II Trial of Napabucasin and Pembrolizumab in Patients with Metastatic Colorectal Cancer (EPOC1503/SCOOP Trial)
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 5887
OP 5894
DO 10.1158/1078-0432.CCR-20-1803
VO 26
IS 22
A1 Kawazoe, Akihito
A1 Kuboki, Yasutoshi
A1 Shinozaki, Eiji
A1 Hara, Hiroki
A1 Nishina, Tomohiro
A1 Komatsu, Yoshito
A1 Yuki, Satoshi
A1 Wakabayashi, Masashi
A1 Nomura, Shogo
A1 Sato, Akihiro
A1 Kuwata, Takeshi
A1 Kawazu, Masahito
A1 Mano, Hiroyuki
A1 Togashi, Yosuke
A1 Nishikawa, Hiroyoshi
A1 Yoshino, Takayuki
YR 2020
UL http://clincancerres.aacrjournals.org/content/26/22/5887.abstract
AB Purpose: This is a phase I/II trial to assess the efficacy and safety of napabucasin plus pembrolizumab for metastatic colorectal cancer (mCRC).Patients and Methods: 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.Results: 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.Conclusions: 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