TQB2618 plus penpulimab, alone or in combination with chemotherapy, for recurrent or metastatic nasopharyngeal carcinoma: a multicentre, two-cohort, phase 2 trial.

Abstract

To evaluate the efficacy and safety of dual immunotherapy blocking T-cell immunoglobulin and mucin-domain containing protein-3 (TIM-3) and programmed cell death protein-1 (PD-1) in recurrent/metastatic nasopharyngeal carcinoma. The TP cohort enrolled patients with progression on prior PD-(L)1 blockade to receive intravenous TQB2618 plus penpulimab every 3 weeks. The TPGC cohort enrolled treatment-naïve patients to receive TQB2618, penpulimab, gemcitabine, and cisplatin every 3 weeks for 4-6 cycles, followed by maintenance dual immunotherapy. Primary endpoints were dose-limiting toxicity and objective response rate for the TP cohort, and progression-free survival for the TPGC cohort. This two-cohort trial is registered with ClinicalTrials.gov, NCT05563480. Between November 2022 and October 2023, 17 patients were enrolled in the TP cohort and 30 in the TPGC cohort. No dose-limiting toxicities were observed. In the TP cohort, disease control was achieved in ten (58.8%) of 17 patients, with no complete or partial responses; median progression-free survival was 1.6 months (95% CI, 0.0-3.2). In the TPGC cohort, objective response rate was 86.2%, including four (13.8%) complete responses. Median progression-free survival was 10.8 months (95% CI, 9.6-16.4), with a 12-month rate of 40.9%; median overall survival was unreached. Grade 3-4 treatment-related adverse events occurred in two (11.8%) patients in the TP cohort and 25 (83.3%) in the TPGC cohort, predominantly hematological toxicities. TQB2618 plus penpulimab combined with gemcitabine-cisplatin demonstrated encouraging antitumor activity and a manageable safety profile in treatment-naïve patients. However, the chemotherapy-free dual regimen showed limited efficacy in immunotherapy-refractory disease.