Efficacy and Safety of Camrelizumab Plus Apatinib in Patients With Refractory Chordoma: A Phase II Clinical Trial

PURPOSE Limited efficacy of current treatments for chordoma calls for novel therapeutic options. Combination of immune checkpoint inhibitors and antiangiogenic drugs has altered the landscape of cancer treatment but has rarely been investigated in chordoma. METHODS An investigator-initiated, single-center, phase II trial was conducted on camrelizumab (a PD-1 inhibitor, 200 mg once every 2 weeks) plus apatinib (an antiangiogenic drug, 250 mg and 500 mg on alternate days, that is, 250 mg one day, 500 mg the next day, alternating) in patients with refractory chordoma for 4-week cycles. The primary end point was the objective response rate (ORR) per RECIST version 1.1. Secondary end points included ORR per Choi criteria, progression-free survival (PFS), overall survival, the disease control rate, median duration of response (mDoR), safety, and quality of life. The trial is registered with Chictr.org.cn (ChiCTR2100042938). RESULTS Of the 38 patients initially screened between September 2021 and October 2024, 33 were enrolled. Median follow-up duration was 20.8 months (IQR, 13.35-26.55). ORR was 24.2% (8/33 [95% CI, 11.1 to 42.3]) per RECIST 1.1 and 48.5% (16/33 [95% CI, 30.8 to 66.5]) per Choi criteria. The median PFS was 28.4 months (95% CI, 13.53 to 43.28). The mDoR was not reached per RECIST 1.1 and was 22.2 months (95% CI, 12.5 to not reached) per Choi criteria. CDKN2A copy-number deletion or homozygous deletion was found to associate with worse prognosis. The most common grade 3 or 4 treatment-related adverse events included increased aspartate aminotransferase (13 [39.4%]) and increased alanine aminotransferase (11 [33.3%]). No treatment-related deaths occurred. CONCLUSION Combination of camrelizumab and apatinib offered encouraging efficacy with manageable toxicity in chordoma treatment. CDKN2A alterations are associated with worse prognosis and may prove to be a potential biomarker for treatment selection.