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. (March 2023)

• Record Type: Journal Article
• Authors: Guo, Ye; Zhang, Weijie; Ying, Jieer; Zhang, Yanqiao; Pan, Yueyin; Qiu, Wensheng; Fan, Qingxia; Xu, Qi; Ma, Yue; Wang, Gang; Guo, Jing; Su, Weiguo; Fan, Songhua; Tan, Panfeng; Wang, Yan; Luo, Yang; Zhou, Hui; Li, Jin
• Is Part Of: European journal of cancer. Volume 181(2023)
• Page Start: 26
• Page End: 37
• Publication Date: 2023-03
• Subjects: Fruquintinib -- Sintilimab -- Advanced solid tumors -- Metastatic colorectal cancer; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2022.12.004
• Languages: English
• ISSNs: 0959-8049

Abstract

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. Highlights: Fruquintinib plus sintilimab was tolerated in patients with advanced solid tumour. Fruquintinib plus sintilimab showed anti-tumour activity in patients with metastatic colorectal cancer. The combination had promising clinical activity in patients with mismatch repair-proficient metastatic colorectal cancer.