GenFleet Therapeutics (GenFleet) released updated Phase II data for its oral KRAS G12D inhibitor GFH375 at the 2026 World Conference on Lung Cancer in Seoul, highlighting a 59.2% objective response rate (ORR) and a 93% disease control rate (DCR) in heavily pre-treated non-small cell lung cancer (NSCLC) patients.

A total of 75 patients with KRAS G12D-mutant NSCLC received GFH375 600 mg once daily; 98.7% had distant metastases and 42.7% had undergone at least two prior treatment lines. As of the 4 September 2026 data cut-off, 71 patients had undergone at least one post-treatment assessment, delivering a 52.1% confirmed ORR (cORR). Median progression-free survival (mPFS) was 8.30 months across the intent-to-treat population and 8.10 months among taxane-pretreated patients. In taxane-naïve patients, mPFS reached 9.60 months with a median follow-up of 11 months. The 12-month overall survival rate stood at 77% after a median 11.20-month follow-up, while median overall survival had not been reached.

Safety remained manageable in all 75 treated patients, with diarrhea, vomiting and nausea reported most frequently and primarily at Grade 1–2 severity. Grade ≥3 treatment-related adverse events (TRAEs) were limited mainly to diarrhea and elevated ALT; no TRAE-related deaths occurred. Patients who had received immune-checkpoint inhibitors (ICI) within 90 days before GFH375 initiation exhibited higher rates of Grade ≥3 hepatotoxicity (16.7% versus 0% in those with earlier ICI exposure).

GFH375 is the first oral KRAS G12D inhibitor to obtain Breakthrough Therapy Designation in China for pretreated NSCLC and entered the global Phase III “Kylin-Flight 01” trial in 2026. Under a January 2025 licensing agreement, Verastem Oncology holds development and commercialization rights for GFH375 outside China, while GenFleet retains domestic rights as part of a broader RAS/MAPK-focused pipeline.