RecruitingPhase 1Phase 2NCT07259590

A Study of GFH375 Combined With Cetuximab or Chemotherapy in Participants With Solid Tumors Harboring KRAS G12D Mutation

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


Sponsor

Genfleet Therapeutics (Shanghai) Inc.

Enrollment

126 participants

Start Date

Oct 21, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

This is a Phase Ib/II clinical study aimed at exploring the safety and efficacy of Regimen A (GFH375 in combination with Cetuximab) and Regimen B (GFH375 in combination with AG) in participants with solid tumors.Phase Ib: To evaluate the safety/tolerability and pharmacokinetic (PK) characteristics of GFH375 in combination with cetuximab or AG in participants with solid tumors, and to explore the efficacy of the combination therapy. Phase II: To evaluate the efficacy, safety/tolerability and PK characteristics of the combination therapy, and to explore the correlation between bio-marker and clinical efficacy.


Eligibility

Min Age: 18 Years

Inclusion Criteria7

  • Voluntarily participate in the study and sign the informed consent form.
  • 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.
  • Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors, with KRAS G12D mutation.
  • Failed standard systemic treatment, or intolerant to standard treatment, or unsuitable for standard treatment, or no standard treatment available.
  • At least one measurable lesions according to RECIST v1.1
  • 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.
  • Have sufficient organ function.

Exclusion Criteria10

  • Symptomatic brain metastasis, leptomeningeal metastasis, spinal cord compression, or primary brain tumor.
  • Presence of known coexisting other cancer driver genes.
  • Previous or active history of clinically significant cardiovascular dysfunction.
  • Presence of active infection.
  • History of central nervous system (CNS) diseases.
  • Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonitis requiring treatment.
  • Newly diagnosed deep vein thrombosis or pulmonary embolism within 3 months before the first administration of the study treatment.
  • Presence of uncontrolled or symptomatic pleural effusion, ascites, or pericardial effusion.
  • 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.
  • 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.

Interventions

COMBINATION_PRODUCTGFH375

GFH375 once daily (QD) .Cetuximab will be administered via intravenous infusion at a dose of 500 mg/m² every 2 weeks.

COMBINATION_PRODUCTGFH375

GFH375 once daily (QD). Paclitaxel (albumin-bound) at 125 mg/m² and gemcitabine at 1000 mg/m² will be administered via intravenous infusion on Days 1, 8, and 15 of each 4-week cycle.


Locations(4)

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

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NCT07259590


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