Camrelizumab Plus Apatinib Demonstrates Encoruaging Activity in Patients With Refractory Chordoma

Clinical Summary:

• Design/Population: This investigator-initiated phase 2 trial evaluated camrelizumab plus apatinib in patients with refractory chordoma. 
• Key Outcomes: The combination demonstrated encouraging response rates, prolonged progression-free survival, and durable response with manageable toxicity. CDKN2A alterations were associated with poorer outcomes.
• Clinical Relevance: These findings support further evaluation of combined PD-1 inhibition and antiangiogenic therapy in chordoma and identify CDKN2A as a potential prognostic biomarker.

According to results from an investigator-initiated phase 2 study, camrelizumab plus apatinib demonstrated encouraging efficacy and durable disease control among patients with refractory chordoma.

The “limited efficacy of current treatments for chordoma calls for novel therapeutic options,” stated Cheng Yang, MD, Second Affiliated Hospital of Naval Medical University, Shanghai, China, and coauthors. The “combination of immune checkpoint inhibitors and antiangiogenic drugs has altered the landscape of cancer treatment but has rarely been investigated in chordoma.” 

In this single-center trial, 33 patients with chordoma that was either unresectable or not amenable to radical surgery received 200 mg of intravenous camrelizumab once every 2 weeks with alternating doses of 250 mg and 500 mg of apatinib every other day in 4-week cycles until spinal cord progression, unacceptable toxicity, or no further clinical benefit. The primary end point was objective response rate (ORR), assessed via RECIST version 1.1. Key secondary end points included ORR (assessed via Choi criteria), progression-free survival (PFS), overall survival (OS), disease control rate, duration of response, and safety. 

At a median follow-up of 20.8 months, the confirmed ORR was 24.2%, as assessed via RECIST version 1.1. Median time to response was 6 months and the median duration of response was not reached. The disease control rate was 90.9%, with a median PFS of 28.4 months. The 6- and 12-month PFS rates were 84.4% and 70%, respectively. 

As assessed via Choi criteria, the confirmed ORR was 48.5%. Median time to response was 2.5 months and the median duration of response was 22.2 months. The disease control rate was 81.8%, with a median PFS of 15.3 months. The 6- and 12-month PFS rates were 78.3% and 69.1%, respectively. 

During the follow-up period, 2 patients died due to tumor progression. Two patients underwent salvage surgical resection following treatment discontinuation; however, both patients died due to postoperative complications. Median OS was not reached. 

Exploratory biomarker analyses demonstrated that all sequenced tumors were PD-L1–negative, microsatellite stable, and had low tumor mutational burden. CDKN2A copy-number loss or homozygous deletion was associated with significantly lower response and shorter PFS, suggesting that CDKN2A alterations may serve as a prognostic biomarker in patients treated with camrelizumab plus apatinib.

Treatment-related adverse events were reported in 93.9% of patients with grade 3/4 events reported in 60.6% of patients. The most common grade 3/4 treatment-related adverse events were increased aspartate aminotransferase (39.4%) and increased alanine aminotransferase (33.3%). Treatment-related adverse events led to 13 apatinib interruptions, including 6 dose reductions, and 7 camrelizumab interruptions. Recurrent AST/ALT elevation led to 4 treatment discontinuations. No treatment-related deaths were reported. 

“Our findings suggest the encouraging antitumor activity and manageable safety profile of camrelizumab plus apatinib in patients with refractory chordoma,” concluded Dr Yang et al.  “Importantly, we identified CDKN2A genomic alterations as a potential negative prognostic biomarker, which could assist treatment selection and decision making in the future treatment of chordoma.” 

“These data establish use of a vascular endothelial growth factor receptor-targeted kinase inhibitor and immunotherapy in a prospective trial in recurrent or metastatic disease and set a standard for future randomized trials,” added Journal of Clinical Oncology associate editor Robert Maki, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York. 

Source:

Yang C, Jia Q, Zhao C, et al. Efficacy and safety of camrelizumab plus apatinib in patients With refractory chordoma: A phase II clinical trial. J Clin Oncol.  Published online: May 13, 2026. doi:10.1200/jco-25-02719