Abstract 666P
Background
Retrospective studies suggest benefits of immunotherapy plus radiotherapy for brain metastases (BM) in NSCLC. CTONG 2003 is the first RCT to assess first-line camrelizumab versus placebo for BM in NSCLC.
Methods
CTONG 2003 is a multicenter, randomized, double-blind, placebo-controlled trial conducted at 15 sites in China. Treatment-naïve NSCLC patients with BM and no EGFR/ALK alterations were randomized 1:1 to receive camrelizumab (200 mg) or placebo, plus platinum-doublet chemotherapy on day 1 of each 3-week cycle for 4-6 cycles, followed by maintenance camrelizumab or placebo ± pemetrexed (500 mg/m2) for up to 31 cycles. SRT or WBRT was administered for BM within 42 days of the first dose, if necessary. Stratification factors included histology (squamous vs. non-squamous), BM lesion number (1-5 vs. ≥6), and radiotherapy use (yes vs. no). Co-primary endpoints were intracranial PFS (iPFS) and PFS. Planned enrollment was 200, but recruitment was terminated early due to therapeutic paradigm shifts in China.
Results
Between May 28, 2021, and July 21, 2023, 60 patients were randomized: 32 to camrelizumab and 28 to placebo. Radiotherapy was given to 65.6% of the camrelizumab group and 82.1% of the placebo group. As of July 8, 2024, median follow-up was 20.5 months (95% CI: 15.1-23.7). Median iPFS was 12.7 months (95% CI: 7.1-25.3) for camrelizumab versus 9.9 months (95% CI: 6.3-14.6) for placebo (HR: 0.45, 95% CI: 0.21-0.97). Median PFS was 9.7 months (95% CI: 6.6-14.0) versus 6.7 months (95% CI: 4.1-8.6; HR: 0.56 [95% CI: 0.29-1.09]). OS trends also favored camrelizumab (HR: 0.59, 95% CI: 0.25-1.39). iORR was 56.3% for camrelizumab versus 42.9% for placebo, with median iDoR of 16.3 months (95% CI: 5.7-21.2) versus 7.1 months (95% CI: 3.9-15.9). ORR were 65.6% versus 32.1%, with median DoR of 8.9 months (95% CI: 5.7-17.0) versus 4.2 months (95% CI: 2.8-7.1). Grade ≥3 TRAEs occurred in 56.3% of the camrelizumab group and 50.0% of the placebo group, primarily neutropenia (31.3% vs. 25.0%) and anemia (25.0% vs. 21.4%).
Conclusions
Despite early termination, camrelizumab showed trends toward improved iPFS and PFS in NSCLC patients with BM, with manageable toxicities.
Clinical trial identification
NCT04768075; 2021-02-24.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J. Lv: Financial Interests, Personal, Affiliate: Jiangsu Hengrui Pharmaceuticals. All other authors have declared no conflicts of interest.