893P - 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

Background

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.

Methods

This was an open-label, single-arm, phase II study for systemic chemotherapy and anti-PD-1 therapy-resistant RM-NPC patients. Enrolled patients received cadonilimab (10mg/kg, day 1) plus TPC chemotherapy (NAB-paclitaxel; cisplatin or lobaplatin; and capecitabine) every 3 weeks for up to 6 cycles, followed by cadonilimab plus capecitabine every 3 weeks for a maximum of 2 years. The primary endpoint was objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS), time to response (TTR), duration of response (DoR), and safety.

Results

Between February 15, 2023 and June 28, 2023, a total of 25 patients were enrolled (median age, 44 years). There were 20% patients who had previously received two or more different PD-1 inhibitors. Up to March 25, 2024, the median follow-up was 10.2 months (range, 4.3 – 13.7 months). The ORR was 68% (95% CI, 48 - 88%), with 3 complete response (12%), 14 partial response (56%). The median DoR was 9.1 months (95% CI, 3.8 – 14.5 months). The median PFS was 10.6 months (95% CI, 5.2 – 16.1 month). The median OS has not yet been reached. Grade 3 or 4 treatment-related adverse events occurred in 12 patients (48%), with the most common being anemia (24%), neutropenia (24%), thrombocytopenia (16%), hypoaesthesia (8%), fatigue (8%), leukopenia (8%), rash (8%), and febrile neutropenia (8%). The most common immune-related adverse events (irAEs) were grade 1-2 thyroid‘stimulating hormone elevation (40%). One patient experienced grade 3 immune-related rash and another patient had grade 3 immune-related lipase increase. No treatment-related death occurred.

Conclusions

Cadonilimab in combination with TPC chemotherapy demonstrated satisfactory antitumoral efficacy and manageable toxicities in patients with RM-NPC who failed at least one line of systemic chemotherapy and anti-PD-1 therapy.

Clinical trial identification

Editorial acknowledgement

Funding

Kangfang Pharmaceutical Co, Ltd.

Disclosure

All authors have declared no conflicts of interest.