Phase Ib study of anti-EGFR antibody (SCT200) in combination with anti-PD-1 antibody (SCT-I10A) for patients with RAS/BRAF wild-type metastatic colorectal cancer

Cancer Biol Med. 2023 Dec 23;21(7):636-650. doi: 10.20892/j.issn.2095-3941.2023.0301.

Abstract

Objective: This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor (EGFR) antibody (SCT200) and an anti-programmed cell death 1 (PD-1) antibody (SCT-I10A) as third-line or subsequent therapies in patients with rat sarcoma viral oncogene (RAS)/v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (wt) metastatic colorectal cancer (mCRC).

Methods: We conducted a multicenter, open-label, phase Ib clinical trial. Patients with histologically confirmed RAS/BRAF wt mCRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200. The primary endpoints were the objective response rate (ORR) and safety. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

Results: Twenty-one patients were enrolled in the study through January 28, 2023. The ORR was 28.57% and the DCR was 85.71% (18/21). The median PFS and OS were 4.14 and 12.84 months, respectively. The treatment-related adverse events (TRAEs) were tolerable. Moreover, compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt mCRC in a third-line setting, no significant improvements in PFS and OS were observed in the combination group.

Conclusions: SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt mCRC patients with an acceptable safety profile. Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting. (Registration No. NCT04229537).

Keywords: Colorectal cancer; SCT-I10A; SCT200; epidermal growth factor receptor; programmed cell death 1.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • ErbB Receptors* / antagonists & inhibitors
  • ErbB Receptors* / genetics
  • ErbB Receptors* / immunology
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor* / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor* / immunology
  • Progression-Free Survival
  • Proto-Oncogene Proteins B-raf* / genetics

Substances

  • Proto-Oncogene Proteins B-raf
  • ErbB Receptors
  • BRAF protein, human
  • Programmed Cell Death 1 Receptor
  • Antibodies, Monoclonal, Humanized
  • EGFR protein, human
  • PDCD1 protein, human
  • camrelizumab
  • toripalimab
  • Immune Checkpoint Inhibitors

Associated data

  • ClinicalTrials.gov/NCT04229537