First-Line Camrelizumab Versus Placebo Plus Chemotherapy With or Without Radiotherapy for Brain Metastases in NSCLC: The CTONG 2003 Randomized Placebo-Controlled Trial

J Thorac Oncol. 2025 Jul;20(7):928-940. doi: 10.1016/j.jtho.2025.02.004. Epub 2025 Feb 8.

Abstract

Introduction: Retrospective studies have indicated the potential benefits of immunotherapy for brain metastases (BMs) in NSCLC. To our knowledge, CTONG 2003 is the first randomized controlled trial to evaluate camrelizumab for untreated BM of NSCLC.

Methods: CTONG 2003 is a multicenter, randomized, double-blind, placebo-controlled trial. Treatment-naïve NSCLC with BM, negative for EGFR mutations and ALK fusions, were randomized 1:1 to receive either camrelizumab or placebo, plus platinum-doublet chemotherapy for four to six cycles, followed by maintenance therapy with camrelizumab or placebo with or without pemetrexed for up to 31 cycles. Radiotherapy was administered for BM, if necessary, within 42 days of the first treatment dose. The co-primary endpoints were intracranial progression-free survival (iPFS) and progression-free survival (PFS). The planned enrollment included 200 patients, but recruitment was terminated early because of therapeutic paradigm shifts globally.

Results: Between May 28, 2021, and July 21, 2023, 60 patients were randomized, with 32 assigned to the camrelizumab group and 28 to the placebo group. The median iPFS was 12.7 months (95% confidence interval [CI]: 7.1-25.3) for camrelizumab versus 9.9 months (95% CI: 6.3-14.6) for placebo (hazard ratio = 0.45, 95% CI: 0.21-0.96). The median PFS was 9.7 months (95% CI: 6.6-14.0) for camrelizumab versus 6.7 months (95% CI: 4.1-8.6) for placebo (hazard ratio = 0.57, 95% CI: 0.29-1.11). Grade 3 or higher treatment-related adverse events occurred in 65.6% and 46.4% of the respective groups, mainly neutrophil count decrease and anemia.

Conclusions: Despite early termination, camrelizumab demonstrated a trend toward improved iPFS and PFS in the BM of NSCLC with an acceptable safety profile.

Trial registration: ClinicalTrials.gov Identifier: NCT04768075.

Keywords: Brain metastases; Camrelizumab; Chemoradiotherapy; Immune checkpoint inhibitors; Non–small cell lung cancer.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / pharmacology
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / secondary
  • Brain Neoplasms* / therapy
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Carcinoma, Non-Small-Cell Lung* / radiotherapy
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • Double-Blind Method
  • Female
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / therapy
  • Male
  • Middle Aged
  • Survival Rate

Substances

  • Antibodies, Monoclonal, Humanized
  • camrelizumab

Associated data

  • ClinicalTrials.gov/NCT04768075