GenFleet Therapeutics announced that updated phase II data of GFH375 monotherapy in pretreated KRAS G12D-mutant non-small cell lung cancer (NSCLC) were released in an oral presentation at the World Conference on Lung Cancer (WCLC) on September 14 local time in Seoul. The presentation demonstrated encouraing efficacy of GFH375 at the 600 mg QD dose level in NSCLC patients, with nearly 100% of enrolled patients having distant metastases and over 40% having received at least two prior lines of therapy. As of the data cutoff date, 71 patients had undergone at least one post-treatment evaluation, 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, the median progression-free survival (mPFS) reached 9.6 months (with median follow-up time of 11 months) among taxane-naïve patients, and the 12-month overall survival rate (OS rate) was 77% (with median follow-up time of 11.2 months) among all patients.
“It is the second selection of GFH375’s NSCLC study data into the WCLC annual meeting, demonstrating encouraging efficacy in a larger patient population for pretreated NSCLC. Building on phase I/II data, GFH375 was the first to have received Breakthrough Therapy Designation (BTD) in China for pretreated KRAS G12D-mutant NSCLC and has entered the world’s first phase III study of an oral KRAS G12D inhibitor in NSCLC (‘Kylin-Flight 01’) this year. GenFleet features a comprehensive RAS-inhibiting portfolio spanning diverse targets, molecular modalities and clinical programs, including GFH375 that is being evaluated in both monotherapy and first-line combination regimens for NSCLC. We are confident in advancing the ‘Kylin-Flight 01’ study and look forward to continued positive progress of multiple GFH375 regimens.”stated Yu Wang, M.D., Ph.D.,Chief Medical Officer of GenFleet.
Oral Presentation: Efficacy and Safety of GFH375 Monotherapy in Advanced KRAS G12D-Mutant NSCLC Patients (Abstract No. 2333)
Presenter: Prof. Ziming Li, Shanghai Chest Hospital
As of September 4, 2026, 75 patients with KRAS G12D-mutant NSCLC were orally administered with GFH375 at 600 mg QD, 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 (ICI) therapy before the enrollment (90.7% had received these two prior therapies concurrently); 42.7% had received at least two prior lines of therapy; 38.7% had received taxanes (including docetaxel); 64% had received ICI therapy within 90 days prior to their first GFH375 dosing. The mPFS was 8.3 months among all the patients and was 8.1 months among taxane-pretreated patients (with median follow-up time of 11 months) ; the median OS (mOS) was not reached (with median follow-up time of 11.2 months) .
As of June 17, 2026, a total of 75 patients treated with GFH375 monotherapy demonstrated manageable safety and tolerability. The most common treatment-related adverse events (TRAEs) included diarrhea, vomiting, and nausea; the majority were graded 1-2 and recovered with supportive treatments. Grade≥3 TRAEs were primarily diarrhea and ALT elevation. TRAEs were generally manageable with no TRAEs-related deaths. No new safety signals were observed compared with previously reported GFH375 monotherapy safety data. The study data suggested that compared with patients taking ICI (anti-PD1/PD-L1 antibody) over 90 days before the first dosing of GFH375, those with ICI exposure within 90 days showed poorer safety and tolerability, especially with higher rates of grade≥3 TRAEs including hepatotoxicity (16.7% vs 0%).
About GFH375/VS-7375
GFH375 is an orally active, potent, highly selective small-molecule KRAS G12D (ON/OFF) inhibitor designed to target the GTP/GDP exchange, thereby disrupting the activation of downstream pathways and effectively inhibiting tumor cell proliferation. Preclinical studies demonstrated dose-dependent inhibition in models bearing KRAS G12D mutation; GFH375 also demonstrated low off-target risk in kinase selectivity and safety target assays.
GenFleet entered into a discovery and development collaboration with Verastem Oncology (Nasdaq: VSTM) to advance three novel oncology discovery programs related to RAS/MAPK pathway-driven cancers. The collaboration provides Verastem with an exclusive option to obtain a license for each of the three compounds in the collaboration after the successful completion of pre-determined milestones in a Phase I trial. Verastem selected GFH375/VS-7375, an oral KRAS G12D (ON/OFF) inhibitor, as its lead program from the collaboration, in December 2023 and the license for GFH375 that was exercised in January 2025 is the first one from this collaboration. The licenses would give Verastem development and commercialization rights outside of China while GenFleet would retain rights inside of China. Outside of China, GenFleet’s partner Verastem Oncology is evaluating VS-7375 in TARGET-D 202, a registration-directed phase 2 study in NSCLC.
GenFleet received the Breakthrough Therapy Designations granted by China’s CDE in 2026 for GFH375 in pretreated KRAS G12D-mutant NSCLC and metastatic pancreatic cancer respectively; Verastem received the Fast Track Designations granted by U.S. FDA for VS-7375 treating KRAS G12D-mutant pancreatic ductal adenocarcinoma across all lines of therapy in 2025, and treating locally advanced unresectable or metastatic KRAS G12D-mutant NSCLC in 2026.
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