GENFLEET-B(02595): GFH375 (oral KRAS G12D inhibitor) Phase II monotherapy superior data in pretreated NSCLC to be presented as an oral presentation at the 2026 World Conference on Lung Cancer

GENFLEET-B(02595) announced that updated Phase II trial data for GFH375 monotherapy in pretreated KRAS G12D-mutant non-small cell lung cancer (NSCLC) were presented as an oral presentation on September 14 local time at this year's World Conference on Lung Cancer (WCLC) held in Seoul. The report demonstrated excellent efficacy of GFH375 at the 600mg QD dose level in NSCLC patients, with nearly 100% of enrolled patients having distant metastases and over 40% having received two or more prior lines of therapy: as of the data cutoff date, 71 patients had completed at least one post-treatment assessment, with an objective response rate (ORR) of 59.2%, a confirmed objective response rate (cORR) of 52.1%, and a disease control rate (DCR) of 93%. In addition, patients who had not previously received taxane-based therapy achieved a median progression-free survival (mPFS) of 9.6 months (median follow-up of 11 months), and the 12-month overall survival rate (12-month OS rate) for all patients was 77% (median follow-up of 11.2 months). Dr. Wang Yu, Chief Medical Officer of GenFleet, stated: "This is the second time that clinical data for GFH375 in the treatment of NSCLC has been selected for WCLC, demonstrating excellent efficacy in treating pretreated NSCLC in a larger patient sample. Based on Phase I/II data, GFH375 was the first in China to receive Breakthrough Therapy Designation (BTD) for pretreated KRAS G12D-mutant NSCLC, and this year entered the world's first Phase III study of an oral KRAS G12D inhibitor for the treatment of NSCLC ('KIRIN-FLY 01'). GenFleet possesses a RAS therapy matrix spanning multiple targets, multiple molecular modalities, and diverse clinical regimens, and the GFH375 NSCLC treatment program also includes monotherapy and first-line combination therapies. We are confident in advancing the 'KIRIN-FLY 01' study and look forward to continued positive progress across multiple therapeutic approaches for this product." As of September 4, 2026, a total of 75 patients with KRAS G12D-mutant NSCLC had received 600mg QD oral GFH375 treatment, of whom 98.7% had distant metastases, including bone metastases (37.3%), brain metastases (16%), and liver metastases (13.3%). All patients had received prior platinum-based chemotherapy and immune checkpoint inhibitor therapy before enrollment (90.7% had previously received both treatments concurrently), 42.7% of patients had received two or more prior lines of therapy before enrollment; 38.7% of patients had previously received taxane-based drugs (including docetaxel), and 64% of patients received immune checkpoint inhibitor (ICI) therapy within 90 days before their first oral dose of GFH375 after enrollment. The mPFS for all patients was 8.3 months, the mPFS for patients who had previously received taxane-based therapy was 8.1 months, and the median overall survival (mOS) had not been reached. As of June 17, 2026, 75 patients receiving GFH375 monotherapy showed manageable safety/tolerability. Most treatment-related adverse events (TRAEs) were Grade 1-2, with the most common TRAEs including diarrhea, vomiting, and nausea, most of which resolved after supportive treatment; Grade 3 and above TRAEs were mainly diarrhea and ALT elevation, and TRAEs were generally manageable, with no TRAEs leading to death; compared with previously reported safety data for GFH375 monotherapy, no new safety signals emerged. The study data suggest that if patients received ICI (PD-1/PD-L1 monoclonal antibody) therapy within 90 days before their first oral dose of GFH375, their safety/tolerability was inferior to that of the patient population with an interval of more than 90 days between the two treatments, particularly manifested in a higher incidence of Grade 3 and above hepatotoxicity (16.7% vs 0%) and other TRAEs.