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

November 20, 2025 updated by: Genfleet Therapeutics (Shanghai) Inc.

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 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

126

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China
        • Recruiting
        • Beijing Cancer Hospital
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China
        • Not yet recruiting
        • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
        • Contact:
          • Zhihua Li
    • Henan
      • Zhengzhou, Henan, China
        • Not yet recruiting
        • The First Affiliated Hospital of Zhengzhou University
    • Hubei
      • Wuhan, Hubei, China
        • Not yet recruiting
        • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
        • Contact:
          • Heshui Wu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A：GFH375 in combination with Cetuximab
Arm A will enroll participants with locally advanced or metastatic solid tumors with KRAS G12D mutation.
Combination product: GFH375
GFH375 once daily (QD) .Cetuximab will be administered via intravenous infusion at a dose of 500 mg/m² every 2 weeks.
Other Names:
  • Cetuximab
Combination product: GFH375
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.
Other Names:
  • gemcitabine
  • Paclitaxel (albumin-bound)
Experimental: Arm B：GFH375 in combination with AG
Arm B will enroll participants with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) with KRAS G12D mutation.
Combination product: GFH375
GFH375 once daily (QD) .Cetuximab will be administered via intravenous infusion at a dose of 500 mg/m² every 2 weeks.
Other Names:
  • Cetuximab
Combination product: GFH375
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.
Other Names:
  • gemcitabine
  • Paclitaxel (albumin-bound)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Phase Ib: Incidence of Dose-Limiting Toxicity (DLT) Events
Time Frame: up to 28 days
up to 28 days
Phase Ib: Incidence and Severity of Adverse Events (AE) and Serious Adverse Events (SAE)
Time Frame: From the first dose until 30 days after the last dose, assessed up to 24 months
From the first dose until 30 days after the last dose, assessed up to 24 months
Phase II: Objective Response Rate (ORR) Evaluated by RECIST 1.1
Time Frame: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma concentrations of GFH375
Time Frame: up to 6 months
Plasma concentrations of GFH375
up to 6 months
Phase II: Incidence and Severity of AE and SAE
Time Frame: From the first dose until 30 days after the last dose, assessed up to 24 months
From the first dose until 30 days after the last dose, assessed up to 24 months
DCR
Time Frame: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
DCR assessed by investigators
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
TTR
Time Frame: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
TTR assessed by investigators
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
DOR
Time Frame: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
DoR assessed by investigators
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
PFS
Time Frame: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, as Determined by investagors
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
OS
Time Frame: From the first dose until date of death from any cause, assessed up to 24 months
Overall Survival
From the first dose until date of death from any cause, assessed up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genfleet Therapeutics (Shanghai) Inc.

Investigators

  • Principal Investigator: Lin Shen, MD, Peking University Cancer Hospital & Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 21, 2025

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

July 1, 2027

Study Registration Dates

First Submitted

November 14, 2025

First Submitted That Met QC Criteria

November 20, 2025

First Posted (Actual)

December 2, 2025

Study Record Updates

Last Update Posted (Actual)

December 2, 2025

Last Update Submitted That Met QC Criteria

November 20, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GFH375X1202

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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