Serplulimab Combination May Be Effective First-line Option for Metastatic Colorectal Cancer

A novel combination regimen involving serplulimab, a PD-1 inhibitor, may be a promising first-line treatment option for patients with metastatic colorectal cancer (mCRC), according to results of a phase 2/3 study presented at the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

While immunotherapy has demonstrated the ability to improve survival in patients with mismatch repair deficient/microsatellite instability-high mCRC, whether the addition of immunotherapy to the standard of care can improve efficacy in proficient mismatch repair/microsatellite stable (pMMR/MSS) mCRC is unclear.

Rui-Hua Xu, MD, PhD, and colleagues designed a randomized, double-blind, multicenter, phase 2/3 study to compare the efficacy of serplulimab (300 mg intravenously every 3 weeks) plus HLX04 (7.5 mg/kg intravenously every 3 weeks)—a biosimilar to bevacizumab—and XELOX (group A) versus placebo plus bevacizumab and XELOX (group B) as a first-line treatment for mCRC. A total of 114 patients were randomized (1:1) from July 2021 to January 2022 and were stratified by PD-L1 expression level (combined positive score [CPS] <1 vs ≥1 and CPS <50 vs CPS ≥50), Eastern Cooperative Oncology Group performance status score (0 vs 1), and primary tumor site (left- vs right-sided).

The primary end point of the analysis was independent radiological review committee-assessed progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors v1.1. Secondary end points included other efficacy end points, safety, pharmacokinetics, biomarker explorations, and quality-of-life assessments.

As of the June 1, 2023, data cutoff, the median follow-up duration in the intention-to-treat population was 17.7 months. Median PFS was 17.2 months in group A versus 10.7 months in group B (hazard ratio [HR], 0.60; 95% CI, 0.31-1.14). The median overall survival was not reached in either group (HR, 0.77; 95% CI, 0.41-1.45).

Grade 3 or higher treatment-related adverse events (TRAEs) were reported in 65.5% and 56.1% of patients in group A and group B, respectively. Most common among these reported TRAEs were decreased neutrophil count (21.8% vs 10.5%, respectively) and decreased platelet count (16.4% vs 10.5%, respectively).

Grade 3 or higher immune-related AEs were reported in 9.1% and 1.8% of patients in group A and group B, respectively. Researchers acknowledged that treatment-related deaths occurred in 4 patients in group A and 3 patients in group B.

These results led Dr. Xu and colleagues to conclude that “serplulimab plus HLX04 and XELOX is a promising first-line treatment option for mCRC patients that warrants further investigation.”