Combination of cadonilimab (anti-PD-1 and CTLA-4 bispecific antibody) with chemotherapy in anti-PD-1 resistant recurrent or metastatic nasopharyngeal carcinoma: an open-label, single-arm, phase II clinical trial

Abstract Treatment options are limited for patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) after failure to anti-PD-1 therapy. Cadonilimab (AK104) is a humanized bispecific antibody that targets to PD-1 and CTLA-4. We aimed to evaluate the efficacy and safety of cadonilimab plus TPC chemotherapy (NAB-paclitaxel, cisplatin or lobaplatin, and capecitabine) in patients with RM-NPC who failed to at least one line of systemic chemotherapy and anti-PD-1 therapy. In this phase II clinical trial (ChiCRT2200067057), 25 patients were enrolled and received cadonilimab plus TPC chemotherapy every three weeks for up to six cycles followed by maintenance treatment of cadonilimab plus capecitabine. Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of progression-free survival, overall survival, duration of response, and safety. This trial met its prespecified primary endpoint of ORR (68%, 95% CI, 48-88), with 3 complete response (12%), 14 partial response (56%), 6 stable disease (24%). Grade ≥3 treatment-related adverse events were occurred in 12 (48%) patients, with the most common being anemia (6[24%]) and neutropenia (6[24%]). This phase II trial shows that cadonilimab in combination with TPC chemotherapy demonstrated satisfactory antitumoral efficacy and manageable toxicities in patients with systemic chemotherapy and anti-PD-1 therapy resistance RM-NPC.