TQB2618 plus Penpulimab, Alone or in Combination with Chemotherapy, for Recurrent or Metastatic Nasopharyngeal Carcinoma: A Multicenter, Two-Cohort, Phase II Trial.

PURPOSE: The purpose of this study was 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.

PATIENTS AND

METHODS

The TQB2618 plus penpulimab (TP) cohort enrolled patients with progression on prior PD-1 or programmed cell death ligand-1 blockade to receive intravenous TP every 3 weeks. The TP combined with gemcitabine-cisplatin (TPGC) cohort enrolled treatment-naïve patients to receive TQB2618, penpulimab, gemcitabine, and cisplatin every 3 weeks for four to six cycles, followed by maintenance dual immunotherapy. Primary endpoints were dose-limiting toxicity (DLT) and objective response rate for the TP cohort and progression-free survival (PFS) for the TPGC cohort. This two-cohort trial is registered with ClinicalTrials.gov (NCT05563480).

RESULTS

Between November 2022 and October 2023, 17 patients were enrolled in the TP cohort and 30 in the TPGC cohort. No DLTs were observed. In the TP cohort, disease control was achieved in 10 (58.8%) of 17 patients, with no complete or partial responses; the median PFS was 1.6 months [95% confidence interval (CI), 0-3.2]. In the TPGC cohort, the objective response rate was 86.2%, including 4 (13.8%) complete responses. The median PFS was 10.8 months (95% CI, 9.6-16.4), with a 12-month rate of 40.9%; the median overall survival was unreached. Grade 3 to 4 treatment-related adverse events occurred in 2 (11.8%) patients in the TP cohort and 25 (83.3%) in the TPGC cohort, predominantly hematologic toxicities.

CONCLUSIONS

TP 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.