Camrelizumab plus apatinib in patients with advanced or refractory chordoma: A single-arm, open-label, phase 2 trial.

Abstract

11503 Background: The limited efficacy of current treatments for chordoma underscores the need for novel therapeutic options. Immune checkpoint inhibitors (ICI) have changed the landscape of cancer treatment but are rarely investigated for chordomas. Additionally, no established biomarkers reliably predict the efficacy of ICI and targeted therapies in this context. Methods: This investigator-initiated, single-arm, phase 2 trial evaluated the efficacy and safety of camrelizumab (anti-programmed death 1, PD-1) combined with apatinib (a tyrosine kinase inhibitor) in patients with advanced or refractory chordoma. Eligible patients received camrelizumab (200 mg intravenously every 2 weeks) and apatinib (250/500 mg orally daily) in 28-day cycles. The primary endpoint was objective response rate (ORR) assessed per RECIST 1.1 and Choi criteria. Secondary endpoints were median progression-free survival (PFS), overall survival, disease control rate (DCR) and safety. Next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) were used to explore predictive biomarkers. The trial is registered on Chictr.org.cn (ChiCTR2100042938). Results: Between September 2021, and October 2024, 38 patients were screened, and 33 were enrolled for efficacy and safety analyses. The median treatment duration was 7 months (IQR 4-14), with a median radiologic evaluation time of 10 months (IQR 9-13) and median follow-up of 15 months (IQR 9-22). At data cutoff, 15 (45.5%) patients remained on treatment. Per RECIST 1.1, seven patients (21.2%, [95% CI, 9.0-38.9]) achieved partial response (PR), with a 6-month DCR of 85.2% (23/27). The median PFS was 18.1 months (95% CI, 11.0-28.5). According to Choi criteria, 16 patients (48.5%, [95% CI, 30.8-66.5]) achieved PR, with a 6-month DCR of 77.7% (21/27) and a median PFS of 15.3 months (95% CI, 10.6-NE). Two patients died of tumor progression, and two others with cervical recurrent chordoma died from postoperative complications. NGS analyses revealed copy number deletion (CND) of CDKN2A in 30% (6/20) of cases. Post hoc FISH analysis of 25 specimens identified homozygous deletion (HD) of CDKN2A in 40.0% (10/25), which correlated with poorer outcomes. Adverse events (AEs) occurred in 93.9% (31/33) of patients, with grade 3/4 AEs in 48.5%. Treatment-related AEs led to apatinib dose interruptions in 39.4% and camrelizumab interruptions in 21.2%. Conclusions: The combination of camrelizumab and apatinib demonstrated promising efficacy and manageable toxicity in chordoma treatment. Furthermore, CDKN2A alterations (CND or HD) were associated with poorer outcomes, providing a potential biomarker for therapeutic stratification. Clinical trial information: ChiCTR2100042938 .