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Published on: October 27, 2014
GFH018 and Toripalimab Combination Therapy for Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma:
Lin-Quan Tang1, Sai-Lan Liu1, Muh-Hwa Yang2
1Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
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.
Insights
The combination of GFH018 and toripalimab demonstrated manageable safety and antitumor effects in recurrent/metastatic nasopharyngeal carcinoma (NPC). Patients who had not received prior immune checkpoint inhibitors (ICIs) showed improved outcomes with this novel therapy.
Area of Science:
- Oncology
- Immunotherapy
- Drug Development
Background:
- GFH018 is a novel transforming growth factor beta receptor I (TGFβRI) inhibitor.
- TGFβRI inhibitors can enhance the efficacy of anti-programmed cell death protein 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) therapies.
- Nasopharyngeal carcinoma (NPC) is a challenging malignancy, particularly in its recurrent/metastatic (R/M) setting.
Purpose of the Study:
- To evaluate the safety and efficacy of combining GFH018 with toripalimab in patients with R/M NPC.
- To assess the objective response rate (ORR), progression-free survival (PFS), duration of response (DoR), and safety profile of the combination therapy.
Main Methods:
- A phase Ib/II clinical trial was conducted involving R/M NPC patients with at least one prior standard therapy line.
- Patients received GFH018 (40 or 80 mg) twice daily for 14 days on/14 days off, plus toripalimab (3 mg/kg) intravenously every two weeks.
- Treatment continued until disease progression or unacceptable toxicity, with ORR as the primary endpoint.
Main Results:
- The study accrued 46 patients. The overall objective response rate (ORR) was 26.1%, and the disease control rate (DCR) was 43.5%.
- Median progression-free survival (PFS) was 2.0 months, and median duration of response (DoR) was 7.6 months.
- In patients without prior immune checkpoint inhibitor (ICI) exposure, the ORR was 40%, DCR was 60%, median PFS was 9.0 months, and median DoR was not reached. High CD8+ T cell density correlated with better PFS.
Conclusions:
- The combination of GFH018 and toripalimab demonstrated a manageable toxicity profile in R/M NPC patients.
- The novel combination therapy showed durable antitumor activity, particularly in patients with no prior ICI treatment.
- Further investigation into this therapeutic strategy, especially for ICI-naïve patients, is warranted.
