GFH018 and Toripalimab Combination Therapy for Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: Results from a Phase Ib/II Study

Abstract Purpose: GFH018 is a novel TGF-β type I receptor 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 patients with recurrent/metastatic (R/M) nasopharyngeal carcinoma (NPC). Patients and Methods: This phase Ib/II study included patients with specific solid tumors who had failed at least one prior line of standard therapy. Patients received GFH018 (40 or 80 mg) twice a day for 14 days on/14 days off, combined with toripalimab (3 mg/kg) intravenously every 2 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 with R/M NPC were accrued. The ORR was 26.1% [90% confidence interval (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. In patients previously exposed to ICIs, the ORR was 9.5% (90% CI, 1.7%–27.1%) and the DCR was 23.8% (90% CI, 9.9%–43.7%). High parenchymal CD8+ T-cell density correlated with better PFS in these patients. Data from other solid tumor cohorts will be reported in future analyses. Conclusions: The combination of GFH018 and toripalimab showed a manageable toxicity profile and durable antitumor activity in patients with R/M NPC, especially those without prior ICI exposure.