GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, today announced the preliminary data from phase I clinical study of GFH925 (IBI351) as monotherapy for treating solid tumors will be presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. Discovered by GenFleet and partnered with Innovent Biologics （“Innovent”）(HKEX: 01801); the clinical data of GFH925 dose escalation part of the phase I trial (NCT05005234), currently conducted by Innovent, will be released as a poster at ASCO held from June 3-7th.
Favorable safety/tolerability and promising antitumor activities of GFH925 monotherapy were observed in previously-treated advanced non-small cell lung cancer and colorectal cancer harboring KRASG12C mutation. As data cutoff, the dose escalation is still ongoing. More cumulating data will be presented at the future medical meeting.
Phase I dose-escalation study of GFH925 (IBI351) monotherapy in patients with advanced solid tumors
Poster Presentation, Abstract #: 3110
GFH925 is a novel, irreversible covalent inhibitor of KRASG12C mutation. The NCT05005234 study presented was a first-in-human study conducted in China to evaluate the safety, tolerability and efficacy of GFH925 monotherapy in patients with advanced solid tumors who failed or were intolerant of standard-of-care treatment. As data cutoff (15 April 2022), 31 subjects were enrolled in the study, including 25 patients with non-small cell lung cancer, 5 colorectal cancer and 1 pancreatic cancer. Approximately 30% patients received 3 lines or above prior systemic anticancer therapy. The highlights of the study results are as following:
• Of 21 patients (including 16 non-small cell lung cancer and 5 colorectal cancer) having at least 1 tumor assessment per RECISTv1.1, 9 achieved PR, with investigator assessed ORR 42.9% and DCR 81%.
• Of 12 patients with NSCLC treated at/above doses of 700mg once daily, 6 achieved PR, with investigator assessed ORR 50% and DCR 83.3%.
• Of 5 CRC patients, 2 achieved PR, with investigator assessed ORR 40% and DCR 60%.
• As data cutoff, GFH925 was well tolerated. No DLT was reported and MTD was not reached. Treatment-related adverse events (TRAEs) occurred in 93.5% (29/31) patients and the most common TRAEs were anemia, transferase increased, bilirubin increased, vomiting and diarrhea. The majority of the TRAEs were grade 1-2 with 12.9% (4/31) of patients reporting grade 3 TRAEs. There were no grade 4-5 TRAEs or TRAEs led to treatment discontinuation.
“KRASG12C mutation occurs in about 2~4% of non-small cell lung cancer and 2.5% of colorectal cancer in China, and no KRASG12C inhibitor was approved yet in China. GFH925 (IBI351) is a novel, irreversible covalent inhibitor of KRASG12C mutation. The preliminary data shows the favorable safety and promising activity of GFH925 (IBI351) monotherapy in KRAS G12C mutated advanced solid tumor. We look forward to more positive clinical data from this study, “stated Professor Yi-Long Wu from Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital.
“We are very pleased that at ASCO Annual meeting 2022 our partner will disclose preliminary clinical data, demonstrating good safety/tolerability and promising efficacy of GFH925 as monotherapy for treating advanced non-small cell lung cancer and colorectal cancer patients with KRAS G12C mutation. We are encouraged by the results and GenFleet has started to propel clinical development of GFH925 ex-China as planned. Our company will adhere to serving unmet medical needs and continue to deliver more innovative drugs benefiting patients worldwide,” stated Yu Wang, M.D./Ph.D., Chief Medical Officer of GenFleet.
About GFH925 (IBI351)
Discovered by GenFleet Therapeutics, GFH925 (Innovent R&D code: IBI351) is a novel, orally active, potent KRASG12C inhibitor designed to effectively target the GTP/GDP exchange, an essential step in pathway activation, by modifying the cysteine residue of KRASG12C protein covalently and irreversibly. Preclinical cysteine selectivity studies demonstrated high selectivity of GFH925 towards G12C. Subsequently, GFH925 effectively inhibits the downstream signal pathway to induce tumor cells’ apoptosis and cell cycle arrest. In September 2021, Innovent and GenFleet Therapeutics entered into an exclusive license agreement for the development and commercialization of GFH925 in China (including mainland China, Hong Kong, Macau and Taiwan) with additional option-in rights for global development and commercialization.
