Combination of GFH018 and Toripalimab Provides Desired Efficacy in Advanced Solid Tumor Patients Resulting in Enhanced Anti-tumor activity

Clinical Findings on GFH018 and Toripalimab

Recent studies have confirmed that the TGF-β signaling pathway is essential for controlling the immune-microenvironment in cancer therapies. For patients with a dismal prognosis who have become resistant to prior immunotherapies, drug candidates targeting this pathway present a vitally important approach.

GFH018, a novel TGF-βR1 inhibitor can modulate the tumor immune microenvironment by inhibiting the activity of TGF-βR1 kinase to block the signal transduction of TGF-β.

Toripalimab is an anti-PD-1 monoclonal antibody that inhibits PD-L1 binding to the PD-1 receptor at a specific region, reducing possibilities for tumor cells to evade the immune system and decreasing PD-1 expression on T-cells as a secondary approach of restoring the body's immune response. 

In a multicenter study being initiated by GenFleet, the efficacy, safety and pharmacokinetics was evaluated. The study enrolled the patients that failed at the prior line of therapy, and received 80 mg twice a day 14-day-on/14-day-off GFH018 in combination with toripalimab. As per response evaluation criteria in Solid Tumor, tumor assessment was performed every 8 weeks. In the intention-to-treat population, the primary endpoint measured the incidence of dose-limiting toxicity (DLT) events, and objective response rate (ORR).

According to the results presented at ASCO 2023, the overall response rate (ORR) was 31.3% in 32 patients having post-baseline tumor assessments, while the DCR (Disease Control Rate) was 50%. The median progression-free survival was not reached among 17 patients who had never received ICI treatment; the ORR was 47.1% and the DCR was 64.7%. 15 patients who had previously received ICI treatment had an ORR of 13.3%, a DCR of 33.3%, and a median PFS of 1.4 months.

Four patients that received ICIs previously, discontinued the study without any post-baseline tumor assessment due to any adverse events. Five subjects were premature for tumor evaluation.

As far as safety is concerned, eleven individuals reported ≥ Grade 3 adverse events, while 82.9% patients experienced treatment-related emergent adverse events of any grade. Approximately 13.7% patients experienced immune-related adverse effects; the most common ones were anemia, rash, hyponatraemia, elevated AST, low WBC, and exhaustion. One patient experienced an acute myocardial infarction of Grade 5, which might be due to tumor metastasis, a low immune system, or another ailment.

KOL insights

“The preclinical findings are quite encouraging, GFH018's displayed potent anti-tumor abilities in both vivo and in vitro against cancer cells. Additionally, translational and mechanistic studies have demonstrated how well it interacts with checkpoint inhibitors and the TGF-β signalling pathway. At this time, researchers are optimistic about its potential as a result of the pathway's overexpression in a number of solid tumors” -Expert Opinion.


GFH018 coupled with toripalimab in patients with R/M Nasopharyngeal Carcinoma was well tolerated and showed early effectiveness. The study demonstrated the increased anti-tumor activities of the combination therapy. Also, GFH018 exhibits immunomodulation effects that may enhance the efficacy of ICIs. Overall, these clinical findings support more research in ICI-naive R/M Nasopharyngeal Carcinoma patients.