On November 13, 2022 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, reported the updated results of IBI351 (GFH925) (KRASG12C inhibitor) from a phase Ia clinical trial (NCT05005234) at the 2022 Chinese Society of Clinical Oncology (CSCO) Annual Meeting (Press release, Innovent Biologics, NOV 13, 2022, View Source [SID1234623905]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Phase Ia study of IBI351 (GFH925) monotherapy in patients with advanced solid tumors: updated results
IBI351(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 IBI351 monotherapy in patients with advanced solid tumors who failed or intolerant to standard of care treatment. As data cutoff (29 July 2022), 67 subjects were enrolled in the study, including 61 patients with non-small cell lung cancer (NSCLC), 5 colorectal cancer(CRC) and 1 pancreatic cancer. Approximately 50% patients received 2 lines or above prior systemic anticancer therapy. 37.7% of NSCLC patients had brain metastases. The highlights of the study results were as follows:
Of 55 evaluable NSCLC patients, 28 achieved partial response (PR), with investigator assessed ORR 50.9% and DCR 92.7%. As data cutoff, most patients remained on treatment. Sustained treatment response was observed at low dose of IBI351. Median duration of response (DOR) and median progression free survival (PFS) were not reached yet.
Of 21 patients with NSCLC treated at 600mg BID (the recommended phase 2 dose), better efficacy signal was observed, with investigator assessed ORR 61.9%(13/21) and DCR 100%.
Of 5 CRC patients, 3 achieved PR, with investigator assessed ORR and DCR 60%. 1 pancreatic cancer patient achieved PR in 1st tumor assessment, and remained on treatment.
As data cutoff, IBI351 was well tolerated. No DLT was reported and MTD was not reached. Treatment-related adverse events (TRAEs) occurred in 92.5% (62/67) patients and the most common TRAEs were anemia, transferase increased, bilirubin increased, pruritus and fatigue. The majority of the TRAEs were grade 1-2 with 19.4% (13/67) of patients reporting grade 3 or higher TRAEs. There were no grade 5 TRAEs or TRAEs led to treatment discontinuation.
Favorable safety and tolerability and promising antitumor activity of IBI351 monotherapy were observed in previously-treated advanced NSCLC, CRC and pancreatic cancer harboring KRASG12C mutation. A single arm registrational trial of IBI351 monotherapy in previously-treated advanced non-small cell lung cancer is ongoing. More data will be presented at the future medical meeting.
Professor Yi-Long Wu from Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, stated: "KRAS mutation as the "undruggable" target for decades has become one of the most popular direction for clinical development recently. IBI351 is a novel, irreversible covalent inhibitor of KRASG12C mutation, whose preliminary data of safety and efficacy was reported at 2022 ASCO (Free ASCO Whitepaper). The update data shows the favorable safety and promising activity of IBI351 (GFH925) monotherapy in KRAS G12C mutated advanced solid tumor. We look forward to more positive clinical data from this study. "
Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to present our clinical development updates at the 2022 CSCO, and that IBI351 monotherapy demonstrated encouraging efficacy and safety data in phase Ia study. A single arm registrational trial of IBI351 monotherapy in previously-treated advanced NSCLC is ongoing. We are working to advance into late stage clinical development to explore the potential of IBI351 as monotherapy and in combo-therapy. We are actively exploring next-generation immunotherapies, hoping to benefit more cancer patients."
About IBI351/GFH925 (KRASG12C Inhibitor)
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 IBI351 towards G12C. Subsequently, IBI351 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 IBI351 in China (including mainland China, Hong Kong, Macau and Taiwan) with additional option-in rights for global development and commercialization.