On September 7, 2022 GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, reported the results from phase I study of GFH018 (TGF-β R1 inhibitor) monotherapy (NCT05051241) for treatment of advanced solid tumor will be presented as a poster at the 2022 European Society for Medical Oncology Meeting in Paris on September 12th (Press release, GenFleet Therapeutics, SEP 7, 2022, View Source [SID1234619217]).
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Through an open-label, multicenter study, GFH018 demonstrated a favorable safety/tolerability profile and preliminary efficacy signal among advanced solid tumor patients that failed to respond to prior standard therapies. No dose-limiting toxicities were observed and over 20% patients with different types of cancer achieved stable disease. Two phase II combination studies of GFH018 with PD-1 inhibitor are ongoing with additional data to be presented at medical meetings in the future.
"We are delighted to collaborate with GenFleet in the clinical research of GFH018 as an innovative small-molecule kinase inhibitor designed to specifically target and inhibit TGF-β R1. We are pleased to report the preliminary efficacy signal and good safety/tolerability profile of GFH018 monotherapy and look forward to the further trials in combination studies." said Professor Ye Guo of Shanghai Oriental Hospital.
"It is the first time for GenFleet to present clinical data at ESMO (Free ESMO Whitepaper), which represents a significant milestone in the company’s multi-regional clinical research and global development. We have recently determined the recommended phase II dose and hope to confirm the response of combination therapies in patients with advanced tumors. Moreover, we expect to release more data related to GFH018 in future academic conferences." said Yu Wang, M.D./Ph.D., Chief Medical Officer of GenFleet.
Phase I study of GFH018, a small molecular TGF-β R1 inhibitor, in patients with advanced solid tumor
Poster 437p, Abstract：#1623, Poster Area: Hall 4
This is an open-label, multicenter study comprising of a modified 3 + 3 dose escalation part followed by an expansion part and the starting dose was 5 mg. Eligible patients with advanced solid tumors failed to standard therapies were administrated with GFH018 BID, 14d on/14d off in 28-day cycles. As of Jan. 25, 2022, 39 patients were sequentially enrolled in the dose escalation part. The median lines of prior therapy were≥3. No dose-limiting toxicities were observed, the maximum tolerated dose was not reached, and no patients discontinued the study treatment due to adverse events.
PK of GFH018 was linear and dose-independent with mean half-life in the range of 3.11 hours to 8.30 hours. Of 24 evaluable patients, 5 achieved stable disease. A patient with thymic carcinoma receiving 50 mg achieved a durable stable disease with tumor shrinkage (maximum lesion decreased by 18.4% and has stayed on treatment for 185 days as of the data cut-off date.
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.