GFH018 and toripalimab combination therapy for previously treated recurrent or metastatic nasopharyngeal carcinoma: Results from a phase 1b/2 study

Abstract Purpose: GFH018 is a novel TGFβRI inhibitor, which has been shown to potentiate the antitumor effect of anti-PD-1/PD-L1 blockade. This study aimed to evaluate the safety and efficacy of GFH018 plus toripalimab in recurrent/metastatic (R/M) NPC patients. Patients & Methods: This phase Ib/II study included patients with R/M NPC who had failed at least one prior line of standard therapy. Patients received GFH018 (40 or 80 mg) BID for 14 days on/14 days off, combined with toripalimab (3 mg/kg) intravenously every two weeks on a 28-day cycle. Treatment continued until disease progression or intolerable toxicity. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), duration of response (DoR), and safety. Results: Forty-six patients were were accrued. The ORR was 26.1% (90% CI: 15.8–38.8%), and the disease control rate (DCR) was 43.5% (90% CI: 31.0–56.6%). The median PFS was 2.0 months (90% CI: 1.8–8.9), and the median DoR was 7.6 months (90% CI: 5.6–not reached). In patients without prior immune checkpoint inhibitor (ICI) treatment, the ORR was 40% (90% CI: 23.6–58.3%), and the DCR was 60% (90% CI: 41.7–76.4%). The median PFS was 9.0 months (90% CI: 1.9–not reached), and the median DoR was not reached. High parenchymal CD8+ T cell density correlated with better PFS in these patients. Conclusions: The combination of GFH018 and toripalimab showed a manageable toxicity profile and durable antitumor activity in R/M NPC patients, especially those without prior ICI exposure.