Phase 1b/2 trial of fruquintinib plus sintilimab in treating advanced solid tumours: The dose-escalation and metastatic colorectal cancer cohort in the dose-expansion phases
Ye Guo, Weijie Zhang, Jieer Ying, Yanqiao Zhang, Yueyin Pan, Wensheng Qiu, Qingxia Fan, Qi Xu, Yue Ma, Gang Wang, Jing Guo, Weiguo Su, Songhua Fan, Panfeng Tan, Yan Wang, Yang Luo, Hui Zhou, Jin Li, Ye Guo, Weijie Zhang, Jieer Ying, Yanqiao Zhang, Yueyin Pan, Wensheng Qiu, Qingxia Fan, Qi Xu, Yue Ma, Gang Wang, Jing Guo, Weiguo Su, Songhua Fan, Panfeng Tan, Yan Wang, Yang Luo, Hui Zhou, Jin Li
Abstract
Background: Fruquintinib (anti-vascular endothelial growth factor 1/2/3) plus sintilimab (anti-programmed death-1) demonstrated enhanced anti-tumour effects versus monotherapy in a preclinical study. We investigated the combination in patients with advanced solid tumours, including metastatic colorectal cancer (mCRC).
Methods: In this phase 1b/2, open-label, multi-centre, multi-cohort dose-escalation and dose-expansion study, patients with advanced solid tumours (dose-escalation) or mCRC (one cohort in dose-expansion) received different doses of fruquintinib plus a fixed dose of sintilimab once every 4 weeks (Q4W) or 3 weeks (Q3W). Primary objectives were safety, tolerability, and the preliminary efficacy. This study is registered at ClinicalTrials.gov, NCT03903705.
Findings: By the data cut-off date (30th December 2021), 23 patients were enrolled in the dose-escalation and 37 patients in the mCRC cohort of the dose-expansion; 44 patients with mCRC who received sintilimab Q3W were pooled for analysis. One dose-limiting toxicity event (grade 3 troponin T increased) occurred during the dose escalation. Grade ≥3 treatment-related adverse events occurred in 43.5% and 47.7% of patients in the dose-escalation phase and pooled mCRC analysis, respectively. Among patients treated with the recommended phase 2 dose (fruquintinib 5 mg once daily, 2 weeks on/1 week off, plus sintilimab 200 mg Q3W) in pooled mCRC analysis, the objective response rate was 23.8% (95% CI 8.2-47.2), median progression-free survival was 6.9 months (95% CI 5.4-8.3), and overall survival was 14.8 months (95% CI 8.8-not reached); in patients with mismatch repair-proficient mCRC, these were 20.0% (95% CI 4.3-48.1), 6.9 months (95% CI 4.8-10.1), and 20.0 months (95% CI 8.1-not reached), respectively.
Interpretation: Fruquintinib plus sintilimab was well tolerated in patients with advanced solid tumours and showed promising efficacy in mCRC.
Keywords: Advanced solid tumors; Fruquintinib; Metastatic colorectal cancer; Sintilimab.
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
Source: PubMed