An anti-PD-1 antibody (SCT-I10A) plus anti-EGFR antibody (SCT200) and chemotherapy for RAS/BRAF wild-type metastatic colorectal cancer: A phase Ib study.

Immunotherapy has demonstrated limited efficacy against microsatellite-stable (MSS) metastatic colorectal cancer (mCRC). However, combining epidermal growth factor receptor (EGFR) antibodies with chemotherapy might improve antitumour immune activity. This research evaluated the safety and effectiveness of SCT200 (an anti-EGFR antibody) plus SCT-I10A (an anti-PD-1 inhibitor) with different chemotherapies as first-/second-line therapies for MSS and RAS/BRAF wild-type (WT) mCRC. This open-label, multicentre, phase Ib study tested combination therapies with SCT-I10A, SCT200, and XELOX or IRI regimens in MSS and RAS/BRAF WT mCRC patients. The objective response rate (ORR) and safety were considered primary endpoints. Progression-free survival (PFS), overall survival (OS) and the disease control rate (DCR) served as secondary endpoints of this study. By May 2024, 76 patients were enrolled. Cohort A (first-line) achieved the following: ORR: 78.57 %; DCR: 100 %; mPFS: 12.45 months; and mOS: 25.03 months. Cohort A (second-line) achieved the following: ORR: 63.64 %; DCR: 90.91 %; mPFS: 9.28 months; and mOS: 20.40 months. Cohort B achieved the following: ORR: 37.5 %; DCR: 87.5 %; mPFS: 6.96 months; and mOS: 20.5 months. Additionally, Olink technology was used to analyze the peripheral immune proteome, and the results demonstrated a significant correlation between efficacy and the activation of immune factors. This trial demonstrated the antitumour activity and acceptable safety of combination therapy in MSS and RAS/BRAF WT mCRC. Oxaliplatin may induce greater immune activation, with GZMA and CXCL13 serving as potential prognostic biomarkers. Thus, combining immunotherapy, EGFR inhibitors, and XELOX represents an optimal therapeutic strategy for mCRC.