Efficacy and safety of chidamide in combination with serplulimab and standard third-line treatments in advanced colorectal cancer: A single arm, exploratory phase 2 trial.

Abstract

TPS3637 Background: The efficacy of third line and subsequent treatments for advanced colorectal cancer (mCRC) is suboptimal, and the available drug options are limited. Approximately 95% of mCRC patients belong to the type of satellite stability (MSS), which often shows poor response to single immunotherapy. Previous clinical trials have preliminarily demonstrated that the potential application of combining anti-angiogenesis drugs with immune checkpoint inhibitors (ICIs) in mCRC. Chidamide is an isoform selective inhibitor of histone deacetylase (HDAC). Studies have shown its synergistic effect with PD-1 monoclonal antibody in anti-tumor activity. Therefore, we aim to conduct further investigations centered on the combination of Chidamide+Serplulimab+standard third-line treatments in mCRC. Methods: This prospective, open-label, single-arm, exploratory multi-center clinical trial has been planned to enroll 30 patients with advanced CRC who have progressed after two lines of standard therapies. The key inclusion criteria are: pathologically confirmed colorectal malignancy; age ≥18 years, regardless of gender; estimated survival ≥3 months; ECOG score 0-1; at least one measurable lesion according to iRECIST criteria; requiring third-line or beyond treatment and no prior treatment with PD1 monoclonal antibody, regorafenib/fruquintinib or TAS-102±bevacizumab; adequate major organ function; and signed informed consent and good compliance, agreeing to cooperate with survival follow-up. Enrolled patients receive Chidamide (20mg twice a week), Serplulimab (3mg/kg on day 1 every two weeks), and standard third-line treatments (TAS-102 35mg/m² twice daily on days 1-5 and 8-12 of a 28-day cycle ± bevacizumab 5mg/kg on day 1 every two weeks or regorafenib 120mg daily or fruquintinib 5mg daily for three weeks followed by one week off ).The primary endpoints are safety and objective response rate (ORR) determined by investigators. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate(DCR), PFS rate at 6 months and 12 months, OS rate at 6 months and 12 months, DCR, quality of life score(QoL), and nutritional score PG-SGA. As of February 2024, eight patients have been enrolled in the study. Trial registration number: ChiCTR2300077213. Clinical trial information: ChiCTR2300077213.