Phase I Data of GFH925 Monotherapy Treating CRC Released at ASCO

Jun 06, 2023

GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, today announced the preliminary data of IBI351 (GFH925, KRASG12C inhibitor) was presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. 

Favorable safety/tolerability and promising antitumor activity of GFH925 monotherapy were observed among advanced colorectal cancer (CRC) patients harboring KRASG12C mutation according to preliminary results from a pooled analysis of two phase I studies(NCT05005234, NCT05497336).

So far, GFH925 has received CDE Breakthrough Designation as monotherapy for previously treated advanced non-small cell lung cancer (NSCLC) and colorectal carcinoma patients in Jan 2023 and May 2023 respectively. 

Efficacy and safety of IBI351 monotherapy in metastatic colorectal cancer harboring KRASG12C mutation: preliminary results from a pooled analysis of two Phase 1 studies

Abstract #: 3586

IBI351 (GFH925)is a novel, irreversible covalent inhibitor of KRASG12C mutation. Data presented in ASCO 2023 was from a pooled analysis of two Phase 1 studies (NCT05005234, NCT05497336). As of data cutoff date (Feb 16, 2023), a total of 54 metastatic colorectal cancer patients were included for analysis (including 3 subjects at 700mg QD, 4 subjects at 450mg BID, 46 subjects at 600mg BID and 1 subject at 750mg BID). The study results were as followed: 

 Of 42 evaluable subjects at 600mg BID, ORR was 42.9% (18/42), confirmed ORR was 31.0% (13/42), DCR was 88.1% (37/42). A total of 23 subjects at 600mg BID received ≥2 lines of systematic anticancer therapy prior to enrollment. ORR was 65.2% (15/23), confirmed ORR was 43.5% (10/23), DCR was 87.0% (20/23).

 The median duration of response (DoR) was not reached yet, with a median follow-up of 5.5 months. The 3-month DoR rate was 85.7%. As data cutoff, 92.3% of the confirmed responders were remained on treatment.

 As data cutoff, GFH925 was well tolerated. Treatment-related adverse events (TRAEs) occurred in 87.0% (47/54) subjects and the majority of the TRAEs were grade 1-2. The most common TRAEs were anemia, white blood cell count decreased, pruritus, alanine aminotransferase increased, neutrophil count decreased, aspartate aminotransferase increased, blood bilirubin increased and asthenia. About 18.5% subjects reporting grade 3 TRAEs. There were no grade 4-5 TRAEs or TRAEs led to treatment discontinuation.

According to GLOBOCAN 2020 report, there were over 1.9 million new cases of colorectal cancer worldwide in 2020 and caused over 900,000 deaths. New CRC cases and the number of deaths in China both accounted for about 30% of all CRC patients globally. KRASG12C mutation was commonly seen in about 2.5% of CRC patients and the development of KRAS inhibitors is crucial to cope with the major public health problem in China and across the whole world. 

“The prognosis of advanced colorectal carcinoma patients with KRASG12C mutation is worse than KRAS wild type patients with limited therapeutic options. Currently, there are no approved drugs targeting KRASG12C available on the market in China. GFH925 is a novel, irreversible covalent inhibitor of KRASG12C mutation. The preliminary data shows favorable safety and promising activity of GFH925 monotherapy in KRASG12C mutated advanced colorectal cancer. We look forward to more positive clinical data from this study. " stated by Professor Kefeng Ding from the Second Affiliated Hospital Zhejiang University School of Medicine.

“It’s pleasing to see the preliminary clinical development results of GFH925 among advanced colorectal cancer patients at ASCO. GFH925 has shown encouraging efficacy and a good safety profile in advanced solid tumors and has received Breakthrough Designation by CDE for NSCLC and colorectal cancer. We are expecting more data from trials sponsored by Innovent, and GenFleet will explore more innovative regimens with GFH925 treating CRC in the subsequent studies  for the benefit of global cancer patients. " stated by Yu Wang, M.D.,Ph.D., Chief Medical Officer of GenFleet.


1. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, 2021, CA: A Cancer Journal for Clinicians

2. Disease Burden of Total and Early-Onset Colorectal Cancer in China from 1990 to 2019 and Predictions of Cancer Incidence and Mortality, 2023, Clinical Epidemiology

3. KRAS G12C mutations in Asia: a landscape analysis of 11,951 Chinese tumor samples, 2020, Translational Lung Cancer Research