GenFleet Receives CTAs Approval for Two Phase II Combination Studies of TGF-β R1 Inhibitor (GFH018) with PD-1 Inhibitor

Jul 22, 2022

GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, announced China’s National Medical Products Administration (NMPA) has approved the Clinical Trial Applications (CTAs) for GFH018 in two clinical studies for combination therapies.

One study is a phase Ib/II trial of GFH018 with PD-1 inhibitor treating patients with advanced solid tumors; the other study is a phase II trial of GFH018, PD-1 inhibitor with concurrent chemoradiotherapy treating patients with locally advanced & unresectable NSCLC. GenFleet has completed a phase I trial of GFH018 monotherapy treating solid tumors in early 2022, and the data will soon be published in relevant international medical conference. 

“Pre-clinical in-vivo data have demonstrated desirable anti-tumor effects of GFH018 in combination with PD-1 inhibitors; the combo study(GFH018X0201)being conducted in Australia and China’s Taiwan has completed the dose escalation phase (phase Ib), with the dose expansion phase (phase II) currently ongoing. From this multi-regional, multi-center clinical trial, we expect to collect additional evidence to further confirm the efficacy of combination therapies with GFH018 in cancer patients. In the study of GFH018, PD-1 inhibitor with concurrent chemoradiotherapy(GFH018X1202), we will investigate the combination’s potential in improving the immunosuppressive microenvironment and reducing the side effects from concurrent chemoradiotherapy.” said Yu Wang, M.D./Ph.D., Chief Medical Officer of GenFleet. 

“GFH018 is GenFleet’s first product that has moved into clinical development stage. The progress of GFH018’s multi-regional studies clearly demonstrates GenFleet’s capability in global regulatory registration, patient enrollment and market positioning, and will substantially accelerate GFH018’s global clinical development. TGF-β signaling pathway has been studied as a critical target in multiple solid tumors; however, no drugs have been approved to date for this pathway. GFH018 is a small molecule drug designed to specifically target and inhibit TGF-β R1, and the discovery and development of GFH018 truly reflects GenFleet’s strategy of novel mechanism-focused innovation in drug development. GenFleet expects the development of the GFH018 to bring a novel therapy with great clinical benefit to cancer patients. “said Jiong Lan, Ph.D., Chief Executive Officer of GenFleet.

Both studies are multi-center, single-arm, and open-label trials designed to evaluate the safety/tolerability and efficacy of the GFH018 in combination therapies. Shanghai Oriental Hospital and Sun Yat-Sen University Cancer Center will lead the phase Ib/II study evaluating the combination of GFH018 and anti-PD-1 monoclonal antibody conducted in over 20 domestic hospitals. The safety/tolerability and efficacy of combination of GFH018, anti-PD-1 monoclonal antibody, concurrent chemoradiotherapy will be evaluated in the phase II study, which will be conducted at over 10 hospitals including West China Hospital of Sichuan University, Peking Union Medical College Hospital.  

About GFH018 and TGF-β R1

Developed by GenFleet Therapeutics, GFH018 is an orally administered TGF-β R1 inhibitor and entered into phase I clinical trial in 2019. Preclinical data showed evidence of GFH018's good anti-tumor properties against cancer cells in vivo and in vitro. Besides, translational and mechanistic studies confirmed it effectively acts on TGF-β signaling pathway and synergizes with checkpoint inhibitors.

In the microenvironment of advanced solid tumors, TGF-β signaling pathway can promote epithelial mesenchymal transition (EMT) & metastasis, induce the formation of cancer stem cells and their functional maintenance, inhibit anti-tumor immunity, enhance vasculature and fibrosis, and ultimately result in tumor progression. Among patients of hepatocellular carcinoma, glioma, colorectal cancer, lung cancer, pancreatic cancer, urothelial cancer and other solid tumors, high expression of genes related to TGF-β signaling pathway is frequently discovered in their blood and tumor tissues. The expression level is positively correlated to the malignancy & poor differentiation of tumor and unfavorable prognosis in patients.