On April 17, 2023 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 1 clinical trial (NCT05005234) in an oral presentation at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Innovent Biologics, APR 17, 2023, View Source [SID1234630188]).
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Topic: Phase I study of IBI351 (GFH925) monotherapy in patients with advanced solid tumors: updated results
Main Researcher: Prof. Qing Zhou, Prof. Yi-Long Wu, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital
Abstract Number: CT030
Presentation Date/Time: Monday Apr 17, 2023 2:30 PM – 4:30 PM
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 date (30 November 2022), 74 subjects were enrolled in the study, including 67 patients with non-small cell lung cancer (NSCLC), 6 colorectal cancer (CRC) and 1 pancreatic cancer. In the presentation, we updated safety and efficacy of NSCLC subjects. Approximately 38.8% of NSCLC patients had brain metastases at baseline. The highlights of the study results were as follows:
As of February 10, 2023, of the 67 evaluable NSCLC patients, 41 achieved partial response (PR), with investigator assessed ORR 61.2% and DCR 92.5%. Most patients remained on treatment.
Of 30 patients with NSCLC treated at 600mg BID (the recommended phase 2 dose), better efficacy signal was observed, with investigator assessed ORR 66.7% (confirmed ORR 53.3%) and DCR 96.7%. The mDOR was not reached yet, the 6m DoR rate was 74.5%（95% CI, 39.8-91.7）. The mPFS was 8.2m (PFS events 46.7%), the data is immature yet. The 6m and 9m PFS rate were 58.9%（95% CI, 39.0-74.3） and 47.3%（95% CI, 26.1-65.8, respectively, with a median follow-up of 8.1 months.
As of 30 November 2022, IBI351 was well tolerated. No DLT was reported and MTD was not reached. Treatment-related adverse events (TRAEs) occurred in 94.0% (63/67) patients and the most common TRAEs were anemia, pruritus, transferase increased, asthenia, protein urine present and bilirubin increased. The majority of the TRAEs were grade 1-2 with 31.3% of patients reporting ≥grade 3 TRAEs. There were no TRAEs led to treatment discontinuation or death.
Favorable safety and tolerability and promising antitumor activity of IBI351 monotherapy were observed in previously-treated advanced NSCLC harboring KRASG12C mutation. A single-arm registrational trial of IBI351 monotherapy in previously-treated advanced non-small cell lung cancer is ongoing.
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) and CSCO. The update data shows the favorable safety and promising activity of IBI351 (GFH925) monotherapy in KRAS G12C mutated advanced NSCLC. Median duration of response (DOR) was not reached and the data of median progression free survival (PFS) was immature. 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 2023 AACR (Free AACR Whitepaper), and that IBI351 monotherapy demonstrated encouraging efficacy and safety data in phase I 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 cancer therapies, 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.