GenFleet Therapeutics Presents Updated Phase II Data of GFH375 Monotherapy in Previously Treated KRAS G12D-Mutant NSCLC as Oral Report at 2026 WCLC

GenFleet Therapeutics (2595.HK) announced that updated Phase II trial data for GFH375 monotherapy in previously treated KRAS G12D-mutant non-small cell lung cancer (NSCLC) will be presented as an oral report at the 2026 World Conference on Lung Cancer (WCLC) in Seoul on September 14, 2026. The presentation showcases GFH375's impressive efficacy at the 600 mg once-daily 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, demonstrating 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%. Notably, the median progression-free survival (mPFS) in patients who had not previously received taxane therapy reached 9.6 months (median follow-up: 11 months), while the 12-month overall survival (OS) rate across all patients was 77% (median follow-up: 11.2 months).

"This marks the second time GFH375's clinical data in NSCLC has been selected for WCLC, demonstrating superior efficacy in a larger patient population for the treatment of previously treated NSCLC," said Dr. Yu Wang, Chief Medical Officer of GenFleet Therapeutics. "Based on Phase I/II data, GFH375 has received Breakthrough Therapy Designation (BTD) in China for previously treated KRAS G12D-mutant NSCLC and entered the Phase III 'Qilin-Fei 01' study earlier this year—the world's first Phase III trial of an oral KRAS G12D inhibitor for NSCLC treatment. GenFleet has built a multi-targeted, multi-molecular RAS therapy matrix with diverse clinical regimens, including GFH375 monotherapy and first-line combination therapy for NSCLC. We are confident in advancing the 'Qilin-Fei 01' study and look forward to continued positive progress across multiple therapeutic approaches for this product."

Oral Presentation Details: Efficacy and Safety Data of GFH375 Monotherapy in KRAS G12D-Mutant Advanced Non-Small Cell Lung Cancer (Abstract No. 2333), presented by Professor Ziming Li from Shanghai Chest Hospital.

As of September 4, 2026, a total of 75 patients with KRAS G12D-mutant NSCLC had received 600 mg once-daily oral GFH375 treatment. Among these patients, 98.7% had distant metastases, including bone metastases (37.3%), brain metastases (16%), and liver metastases (13.3%). All patients had previously received platinum-based chemotherapy and immune checkpoint inhibitor therapy (90.7% had concurrently received both treatments), and 42.7% had received two or more prior lines of therapy before enrollment. Additionally, 38.7% of patients had previously received taxane therapy (including docetaxel), and 64% had received immune checkpoint inhibitor (ICI) treatment within 90 days prior to their first oral GFH375 dose after enrollment.

The median progression-free survival (mPFS) across all patients was 8.3 months, with a median follow-up of 11 months. In patients who had previously received taxane therapy, the mPFS was 8.1 months (median follow-up: 11 months). The median overall survival (mOS) had not been reached (median follow-up: 11.2 months).

As of June 17, 2026, safety and tolerability data from 75 patients receiving GFH375 monotherapy demonstrated that the treatment was manageable. Most treatment-related adverse events (TRAEs) were Grade 1-2, with the most common TRAEs including diarrhea, vomiting, and nausea, most of which resolved with supportive treatment. Grade 3 or higher TRAEs were primarily diarrhea and elevated ALT levels. The TRAEs were overall manageable, with no fatal TRAEs reported. Compared to previously reported safety data for GFH375 monotherapy, no new safety signals emerged. Study data suggest that patients who received ICI (PD-1/PD-L1 monoclonal antibody) treatment within 90 days prior to their first oral GFH375 dose had worse safety and tolerability profiles compared to patients with a treatment interval exceeding 90 days, particularly in terms of higher incidence of Grade 3 or higher hepatotoxicity (16.7% vs. 0%) and other TRAEs.

About GFH375/VS-7375

GFH375 is an oral, highly potent, and highly selective small-molecule KRAS G12D (ON/OFF) inhibitor that binds to KRAS G12D protein through a non-covalent mechanism, inhibiting its interaction with downstream effector proteins. This disrupts the sustained activation of downstream pathways by KRAS G12D in cells, ultimately achieving efficient inhibition of tumor cell proliferation. Preclinical studies have demonstrated that GFH375 monotherapy's tumor growth inhibition effect increases with dosage and treatment duration, while showing low off-target risk in kinase selectivity and safety target testing.

In August 2023, GenFleet Therapeutics and Nasdaq-listed Verastem Oncology (NASDAQ: VSTM) reached a licensing and early collaboration agreement for three products developed by GenFleet. In January 2025, Verastem announced the exercise of its option for GFH375/VS-7375, obtaining development and commercialization rights for GFH375 outside Greater China.

GenFleet's partner, Verastem Oncology, has initiated a registration-directed Phase II NSCLC clinical study (TARGET-D 202) overseas.

In 2026, GenFleet Therapeutics received Breakthrough Therapy Designation from China's Center for Drug Evaluation (CDE) for GFH375 in the treatment of previously treated KRAS G12D-mutant metastatic pancreatic cancer. In 2025, Verastem received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for VS-7375 in the treatment of all lines of KRAS G12D-mutant pancreatic ductal adenocarcinoma.

About GenFleet Therapeutics

GenFleet Therapeutics (2595.HK) is a globally-focused innovative drug development company addressing highly unmet clinical needs in oncology and immunological diseases. Leveraging disease biology mechanisms and clinical translational medicine as its core, the company has built and leverages its independent, integrated R&D system to target innovative targets and indications without clinical validation, while maintaining global independent intellectual property rights.

Since its establishment in 2017, GenFleet Therapeutics has built a portfolio including multiple independently developed "global first-in-class" large and small molecule projects, with several products conducting global multi-center clinical trials in China, Europe, and the United States, including multiple late-stage or pivotal clinical studies.

Dabote® (fluzelesib) is the first domestically approved product in GenFleet's pipeline and also the first domestically developed and third globally approved KRAS G12C inhibitor. The company has since formed an integrated deep cultivation matrix of RAS-targeted therapies, including multi-targeted, various molecular types of selective and pan-RAS inhibitors, with multiple products leading in their respective target tracks both domestically and internationally, and research data presented multiple times as breakthrough research abstracts and oral reports at international academic conferences.

Simultaneously, the company is actively expanding development of other "global first-in-class" targeted drugs, employing synergistic mechanisms to create globally pioneering multi-targeted therapies of various types. Combined with innovations in clinical needs and treatment concepts, the company is entering major indication markets including pancreatic cancer, non-small cell lung cancer, and cachexia through its product portfolio.

GenFleet has received National-Level Specialized, Refined, Differential, and Innovative "Little Giant" enterprise recognition, National-Level High-Tech Enterprise certification, and has been recognized as a Shanghai Specialized, Refined, Differential, and Innovative SME, Shanghai Multinational Corporation R&D Center, and Shanghai Enterprise Technology Center. The company has continuously deepened its commercial collaboration network in recent years, having reached strategic licensing agreements with multiple domestic and international listed companies and achieved positive progress in "global first-in-class" clinical collaborations.

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