Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2020 Jun 20;38(18):2053-2061.
doi: 10.1200/JCO.19.03296. Epub 2020 Apr 28.

Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603)

Shota Fukuoka  1   2 , Hiroki Hara  3 , Naoki Takahashi  3 , Takashi Kojima  1 , Akihito Kawazoe  1 , Masako Asayama  3 , Takako Yoshii  3 , Daisuke Kotani  1 , Hitomi Tamura  4 , Yuichi Mikamoto  4 , Nami Hirano  4 , Masashi Wakabayashi  4 , Shogo Nomura  4 , Akihiro Sato  4 , Takeshi Kuwata  5 , Yosuke Togashi  2 , Hiroyoshi Nishikawa  2 , Kohei Shitara  1
Affiliations
Clinical Trial

Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603)

Shota Fukuoka et al. J Clin Oncol. .

Abstract

Purpose: This is a phase Ib trial of regorafenib plus nivolumab for gastric and colorectal cancer.

Patients and methods: Enrolled patients received regorafenib plus nivolumab in a dose-finding part to estimate the maximum tolerated dose. Additional patients were enrolled in a dose-expansion part. Regorafenib of 80-160 mg was administered once daily for 21 days on/7 days off with nivolumab 3 mg/kg every 2 weeks. The primary end point was dose-limiting toxicity (DLT) during the first 4 weeks to estimate the recommended dose.

Results: Fifty patients (25 each with gastric and colorectal cancer) were enrolled. All patients had received ≥ 2 previous lines of chemotherapy, including anti-angiogenetic inhibitors in 96% of patients. Seven patients with gastric cancer had previously been treated with immune checkpoint inhibitors. One patient had microsatellite instability-high colorectal cancer, whereas the remaining patients had microsatellite stable or mismatch repair-proficient tumors. Three DLTs (grade 3 colonic perforation, maculopapular rash, and proteinuria) were observed with regorafenib 160 mg; none were observed with 80 or 120 mg. During the dose-expansion part, regorafenib dose was reduced from 120 to 80 mg because of frequent maculopapular rash. The common grade ≥ 3 treatment-related adverse events were rash (12%), proteinuria (12%), and palmar-plantar erythrodysesthesia (10%). Objective tumor response was observed in 20 patients (40%), including 11 with gastric cancer (44%) and 9 with colorectal cancer (36%). Median progression-free survival was 5.6 and 7.9 months in patients with gastric and colorectal cancer, respectively.

Conclusion: The combination of regorafenib 80 mg plus nivolumab had a manageable safety profile and encouraging antitumor activity in patients with gastric and colorectal cancer, which warrants additional investigations in larger cohorts.

Trial registration: ClinicalTrials.gov NCT03406871.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

Associated data