Multicenter phase 1/2 Trial of napabucasin and pembrolizumab in patients with metastatic colorectal cancer (EPOC1503/SCOOP Trial)

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Akihito KawazoeT Yoshino

Abstract

This is a phase 1/2 trial of napabucasin plus pembrolizumab for metastatic colorectal cancer (mCRC). Phase 1 was conducted to determine the recommended phase 2 dose (RP2D) in a dose escalation design of napabucasin (240mg to 480 mg twice daily) with 200mg pembrolizumab every 3 weeks. Phase 2 included cohort A (n = 10, microsatellite instability high) and cohort B (n = 40, microsatellite stable). 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 1, 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 ...Continue Reading

References

Jan 27, 2011·European Journal of Immunology·Sabine J WölfleKlaus Heeg
Jun 2, 2015·The New England Journal of Medicine·Dung T LeLuis A Diaz
Jun 4, 2015·Statistical Methods in Medical Research·Cornelia U KunzMeinhard Kieser
Oct 13, 2015·Nature Medicine·Justin GuinneySabine Tejpar
Feb 12, 2017·Journal of the National Comprehensive Cancer Network : JNCCN·Jun GongMarwan Fakih
Feb 6, 2018·The Lancet. Gastroenterology & Hepatology·Derek J JonkerChristopher J O'Callaghan
Apr 17, 2018·The New England Journal of Medicine·Matthew D HellmannLuis Paz-Ares
Sep 21, 2018·American Society of Clinical Oncology Educational Book·Michael J OvermanMichael A Morse
Nov 15, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Dung T LeThierry André

❮ Previous
Next ❯

Citations

Sep 23, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Maliha Nusrat
Feb 19, 2021·Expert Opinion on Investigational Drugs·Matteo SantoniNicola Battelli
Apr 6, 2021·Frontiers in Cell and Developmental Biology·Xiangru HuangLingyong Jiang
Jun 29, 2021·Frontiers in Oncology·Yongjiu DaiXiaofeng Qian
May 1, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Keigo ChidaTakayuki Yoshino
Jun 3, 2021·Journal of the National Cancer Institute·Sanne Ten HoornLouis Vermeulen
May 17, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Wen NiJianming Li

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.