GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, today announced the publication of updated clinical data of GFH925 (IBI351, KRAS G12C inhibitor) monotherapy treating non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) at the European Society for Medical Oncology Asia Congress (ESMO Asia) in 2023, held during December 1-3 in Singapore. 

The abstract with results from GFH925 monotherapy treating NSCLC in the registrational phase II study (NCT05005234) was accepted as a LBA (Late-breaking abstracts) program in 2023 ESMO Asia, after the New Drug Application for GFH925 monotherapy treating NSCLC patients was recently accepted by National Medical Products Administration and granted with Priority Review Designation. The data demonstrated encouraging antitumor activity and favorable tolerability of GFH925 among NSCLC patients, with a confirmed objective response rate (assessed by the Independent Imaging Review Committee) meeting the study’s primary endpoint. 

Data of GFH925 monotherapy treating advanced CRC patients in two studies (NCT05005234, NCT05497336) were also announced at the congress; favorable safety/tolerability and promising efficacy were observed among subjects. GFH925 received Breakthrough Therapy Designations treating advanced NSCLC patients and CRC patients harboring KRAS G12C mutation in 2023. 

Presentation title: Efficacy and safety of IBI351 (GFH925), a selective KRAS G12C inhibitor, monotherapy in advanced non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation: initial results from a registrational phase II study

Abstract #: LBA12

IBI351 (GFH925) is a selective, covalent and irreversible KRAS G12C inhibitor. The data presented was from a single-arm Phase 2 registration clinical study (NCT05005234) in advanced NSCLC patients harbouring KRAS G12C mutation who have received at least one systemic therapy. As data cutoff date (June 13, 2023), a total of 116 NSCLC subjects were enrolled and evaluable:

• GFH925 demonstrated encouraging antitumor activity. The confirmed objective response rate assessed by the Independent Imaging Review Committee was 46.6% (95%CI: 37.2-56.0), meeting the primary endpoint. Disease control rate was 90.5% (95%CI: 83.7, 95.2). The median duration of response was 8.3 months, and 53.7% (29/54) of participants with tumor response were still on treatment. Median progression-free survival was 8.3 months (95%CI: 5.6-10.4), and median survival was not yet reached.

• GFH925 was well tolerated in general. As data cutoff, about 90.5% (105/116) of subjects had treatment-related adverse events, most were grade 1-2. The most common TRAEs were anemia, alanine aminotransferase increased, aspartate aminotransferase increased, asthenia and protein urine present. About 40.5% of subjects had grade 3 or higher TRAEs. 

“KRAS mutation as the 'undruggable' target for decades has become one of the most popular direction for clinical development recently. Although FDA has approved KRAS G12C targeted drugs overseas, there's no drug approved in China. GFH925 is China’s first KRAS G12C inhibitor with NDA acceptance. As a selective, covalent and irreversible KRAS G12C inhibitor, GFH925 has demonstrated excellent efficacy and manageable safety in pivotal Phase 2 study. We look forward to the approval of this drug to benefit more NSCLC patients harboring KRAS G12C mutation have received at least one systemic therapy.” stated Professor Yi-Long Wu, Leading Principal Investigator of the study, from Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital. 

Presentation title: Efficacy and safety of IBI351(GFH925) monotherapy in metastatic colorectal cancer harboring KRAS G12C mutation: updated results from a pooled analysis of two phase I studies

Abstract #: 106P

IBI351 (GFH925) is a specific selective, covalent and irreversible KRAS G12C inhibitor. The updated data presented is based on the pooled analysis of two ongoing clinical studies (NCT05005234, NCT05497336) with extended follow-up. As of June 13, 2023, a total of 56 patients with advanced CRC were enrolled (3 in the 700mg QD dose group, 4 in the 450mg BID dose group, 48 in the 600mg BID dose group, and 1 in the 750mg BID dose group).  

• For 600mg BID patients (n=48), confirmed ORR was 45.8% and DCR was 89.6%. Median DoR was not reached, and the 6 month DoR rate was 65.5%. Median PFS was 7.6 months. Median OS has not yet been reached, with a 6month OS rate of 91.1%.

• For 600mg BID patients with at least two lines of prior treatment (n=27), confirmed ORR and DCR were 63.0% and 88.9%, respectively.

•TRAEs occurred in 94.6% patients while majority of them were grade 1-2. The most common TRAEs were anemia, white blood cell count decreased, blood bilirubin increased, pruritus, neutrophil count decreased, aspartate aminotransferase increased, and gamma-glutamyl transferase increased. Grade 3 TRAEs occurred in 23.2% patients. No grade 4-5 TRAEs or TRAEs leading to treatment discontinuation occurred.

 "Advanced colorectal cancer patients with KRAS G12C mutation have poor prognosis and short survival time with limited existing treatment methods; there is an urgent unmet clinical need. GFH925 as a selective covalent irreversible KRAS G12C inhibitor, its monotherapy has demonstrated outstanding efficacy and manageable safety in advanced colorectal cancer with KRAS G12C mutation. We look forward to more positive results update from this study." stated Professor Ying Yuan, Leading Principal Investigator of the study, from the Second Affiliated Hospital of Zhejiang University School of Medicine.