Phase I Data for GFH925 Monotherapy Presented at 2023 AACR-GenFleet Therapeutics

Phase I Data for GFH925 Monotherapy Presented at 2023 AACR

Apr 19, 2023
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GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, today announced the updated results of GFH925 (IBI351) from a Phase I clinical trial (NCT05005234) in an oral presentation at the 2023 American Association for Cancer Research (AACR) Annual Meeting. Favorable safety and tolerability and promising antitumor activity of GFH925 (KRASG12C inhibitor) monotherapy were observed in previously-treated advanced NSCLC harboring KRASG12C mutation. 

The Center for Drug Evaluation of China's National Medical Products Administration has granted Breakthrough Therapy Designation for the product as monotherapy to treat advanced non-small cell lung cancer patients with KRASG12C mutation that have received at least one prior line of systemic therapy.

Aside from the monotherapy, the phase Ib/II study of GFH925 in combination with ERBITUX® (cetuximab) has been approved by European Medicine Agency (EMA). Proposed and operated by GenFleet, the study is expected to target more NSCLC patients that will potentially benefit from this combination therapy in first line setting.


Professor Yi-Long Wu, Guangdong Lung Cancer Institute & Guangdong Provincial People’s Hospital

KRAS mutation as the “undruggable” target for decades has become one of the most popular direction for clinical development recently. GFH925 is a novel, irreversible covalent inhibitor of KRASG12C mutation, whose preliminary data of safety and efficacy was reported at 2022 ASCO and CSCO. The update data shows the favorable safety and promising activity of GFH925 monotherapy in KRASG12C 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. 

Topic: Phase 1 study of IBI351 (GFH925) monotherapy in patients with advanced solid tumors: updated results

•Main Researchers: Prof. Qing Zhou(Leading Site PI), Prof. Yi-Long Wu (Leading PI), Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital

Presenting Author: 

Chongrui Chong, MD, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital

•Abstract Number: CT030

•Presentation Date/Time: Monday Apr 17, 2023 

•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%), data is immature. 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, GFH925 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.