The oral KRAS G12D (ON/OFF) inhibitor was previously granted with FDA’s FTD for the treatment of KRAS G12D-mutant pancreatic ductal adenocarcinoma (PDAC) in 2025. Besides, GFH375 received the first two Breakthrough Therapy Designations in China for monotherapy treating G12D-mutant pancreatic cancer and NSCLC respectively.
GenFleet Therapeutics（2595.HK） announced the updated clinical data of GFH375 monotherapy treating KRAS G12D-mutant solid tumors were presented in the oral abstract session at the 2026 American Society of Clinical Oncology (ASCO) annual meeting on June 1 local time.
Additionally, preliminary clinical data of GFS202A, the world’s first GDF15/IL-6 bispecific antibody developed for cachexia, will be unveiled in a poster session during the conference. The 2026 ASCO annual meeting is slated to take place in Chicago, USA, from May 29 to June 2 local time.
The studies highlighted the potent and differentiated profile of GFH375, an oral KRAS G12D (ON/OFF) inhibitor, demonstrating superior anti-tumor activity, enhanced potency and selectivity, and more durable pathway suppression compared with other KRAS/RAS inhibitors across animal models and cellular assays.
GFS784 links a molecular glue Pan RAS (ON) inhibitor to cetuximab. Preclinical studies showed potent activity in RAS mutant models, both DXd sensitive and DXd resistant models, as well as anti tumor efficacy in EGFR mutant and TKI resistant models, supporting its potential as a monotherapy to deliver superior benefit compared with double-agent combination regimens.
Preclinical research showed at one-third the dosage of RMC 6236, GFH276 exerted comparable or enhanced tumor growth inhibition (TGI) in multiple RAS-mutant tumor models.
As an allosteric activator of the KEAP1-CUL3 complex, GFH603 enhances the formation of KEAP1-CUL3 E3 ligase complex and thereby promotes NRF2 degradation. KEAP1 is a prevalent co-mutated gene in RAS-mutant tumors, and preclinical research demonstrated that GFH603 exerted potent antitumor efficacy both as a single agent and in combination with a Pan RAS inhibitor.
The designation is intended for GFH375 monotherapy treating patients with KRAS G12D-mutant metastatic pancreatic cancer who have received at least one prior systemic therapy, representing China’s first BTD inclusion of KRAS G12D inhibitor monotherapy for pancreatic cancer.
