GFH375 combined with cetuximab or chemotherapy for KRAS G12D–mutant solid tumors

A Multicenter, Open-Label, Phase Ib/II Clinical Study to Explore the Efficacy, Pharmacokinetics and Safety/Tolerability of GFH375 in Combination With Cetuximab or Chemotherapy in Participants With Advanced Solid Tumors Harboring KRAS G12D Mutation

This tests whether adding GFH375 to cetuximab or to standard chemotherapy helps people with advanced solid tumors that have a KRAS G12D mutation.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 126 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Genfleet Therapeutics (Shanghai) Inc. (Industry-sponsored)
• Drugs / interventions: radiation, Cetuximab
• Locations: 4 sites (Beijing, Beijing Municipality and 3 other locations)
• Trial ID: NCT07259590 on ClinicalTrials.gov

What this trial studies

This is a Phase Ib/II trial testing two combination regimens: GFH375 plus cetuximab (Regimen A) and GFH375 plus AG chemotherapy (Regimen B) in patients with advanced, unresectable or metastatic solid tumors harboring KRAS G12D mutations. Phase Ib focuses on safety, tolerability and pharmacokinetics of the combinations while exploring early signs of activity. Phase II expands the evaluation of efficacy, continued safety monitoring and pharmacokinetics, and examines relationships between biomarkers and clinical outcomes. Eligible participants must have measurable disease and have exhausted or be unsuitable for standard treatment options.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically or cytologically confirmed unresectable or metastatic solid tumors with a KRAS G12D mutation, measurable disease by RECIST v1.1, adequate organ function, and who have failed or are unsuitable for standard therapies.

Not a fit: Patients without the KRAS G12D mutation, those with symptomatic brain metastases or other excluded conditions, or those who do not meet the required performance status or organ-function criteria are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this could provide a new targeted treatment option that controls tumor growth in patients with KRAS G12D–mutant cancers.

How similar studies have performed: Targeting KRAS G12D is relatively novel with limited clinical proof to date, though KRAS-directed approaches (notably for G12C) have shown clinical benefit and preclinical data support efforts against G12D.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily participate in the study and sign the informed consent form.
2. Participants receiving Regimen A must be ≥ 18 years old when signing the informed consent form, and participants receiving Arm B must be 18 - 75 years old.
3. Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors, with KRAS G12D mutation.
4. Failed standard systemic treatment, or intolerant to standard treatment, or unsuitable for standard treatment, or no standard treatment available.
5. At least one measurable lesions according to RECIST v1.1
6. Participants receiving Regimen A must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 - 2; participants receiving Regimen B must have an ECOG PS score of 0 - 1.
7. Have sufficient organ function.

Exclusion Criteria:

1. Symptomatic brain metastasis, leptomeningeal metastasis, spinal cord compression, or primary brain tumor.
2. Presence of known coexisting other cancer driver genes.
3. Previous or active history of clinically significant cardiovascular dysfunction.
4. Presence of active infection.
5. History of central nervous system (CNS) diseases.
6. Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonitis requiring treatment.
7. Newly diagnosed deep vein thrombosis or pulmonary embolism within 3 months before the first administration of the study treatment.
8. Presence of uncontrolled or symptomatic pleural effusion, ascites, or pericardial effusion.
9. Having received major surgery within 28 days before the start of the study treatment; having experienced major trauma within 14 days before the start of the study treatment; or planning to undergo major surgery during the study period.
10. Having received radiotherapy within 4 weeks before the start of the study treatment, or having received palliative radiotherapy for bone metastatic lesions within 2 weeks before the start of the study treatment.

Where this trial is running

Beijing, Beijing Municipality and 3 other locations

• Beijing Cancer Hospital — Beijing, Beijing Municipality, China (Recruiting)
• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (Not_yet_recruiting)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Not_yet_recruiting)
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Lin Shen, MD — Peking University Cancer Hospital & Institute
• Study coordinator: Yolanda Zeng

Conditions Advanced Solid Tumors Cancer; PDAC; CRC; solid tumors; KRAS G12D Mutations