Updated efficacy and subgroup analysis of first-line serplulimab plus bevacizumab and XELOX versus placebo plus bevacizumab and XELOX in metastatic colorectal cancer: A phase 2/3 study.
Authors: Rui-Hua Xu, Feng Wang, Zi-Xian Wang, Junjie Peng, Xinjun Liang, Ying Cheng, Yanhong Deng, Kehe Chen, Mingjun Zhang, Jingdong Zhang, Wei Wang, Bangwei Cao, Yongdong Jin, Meili Sun, Yuan Lin, Suxia Luo, Zhen Li, Liu Yang, Qingyu Wang, Jun Zhu
Journal: Journal of Clinical Oncology (2025)

170 Background: This is a randomized, double-blind, multicenter phase 2/3 study comparing the efficacy and safety of serplulimab (a novel anti-PD-1 antibody) plus bevacizumab and XELOX chemotherapy vs. placebo plus bevacizumab and XELOX as first-line treatment for metastatic colorectal cancer (mCRC). Our previous presentation at the 2024 ASCO Meeting showed the progression-free survival results. Here we present the updated efficacy and safety findings together with subgroup analysis results after a median follow-up of 31.0 months. Methods: A total of 114 patients with mCRC and no prior systemic therapy were randomized 1:1 (serplulimab arm, n = 57; placebo arm, n = 57) to receive intravenous (IV) serplulimab (300 mg) plus bevacizumab (7.5 mg/kg) and XELOX (IV oxaliplatin [130 mg/m 2 ] and oral capecitabine [1000 mg/m 2 ]) (group A) or placebo plus bevacizumab and XELOX (group B) once every 3 weeks. Stratification factors were PD-L1 expression level, ECOG PS score, and primary tumor site. The primary endpoint was independent radiological review committee (IRRC)-assessed PFS per RECIST 1.1. Secondary endpoints included other efficacy endpoints, safety, pharmacokinetics, biomarker explorations, and quality-of-life assessments. Results: In the phase 2 part, by the data cutoff of June 30, 2024, sustained improvements in PFS (16.6 vs. 10.7 months, stratified HR 0.66, 95% CI 0.37–1.19) and DOR (17.7 vs. 11.3 months, stratified HR 0.45, 95% CI 0.20–0.98) were observed for patients in group A compared to group B in the modified intent-to-treat population (n = 112; two patients in group A did not receive any intended study treatment). 32/55 (58.2%) patients in group A and 35/57 (61.4%) in group B have died. Median overall survival (OS) was 25.6 months in group A and 21.2 months in group B (stratified HR 0.86, 95% CI 0.53–1.42). A trend of PFS and OS benefits was similarly observed for the patients with a microsatellite stable (MSS) status (PFS: 16.8 vs. 10.1 months, stratified HR 0.65, 95% CI 0.33–1.29; OS: 23.5 vs. 20.2 months, stratified HR 0.79, 95% CI 0.45–1.38). 39 (70.9%) patients in group A and 34 (59.6%) in group B had grade ≥3 treatment-related adverse events. Serplulimab/placebo-related serious TRAEs occurred in 13 (23.6%) patients in group A and 14 (24.6%) patients in group B. Conclusions: With a follow-up duration of 31.0 months, improved survival benefits demonstrated with the addition of serplulimab were maintained in the first-line treatment of mCRC patients including those with MSS status alongside a manageable safety profile. The phase 3 part of this study is currently ongoing to further evaluate serplulimab plus bevacizumab and XELOX as a first-line treatment option in mCRC. Clinical trial information: NCT04547166 .