A Study of GFH375 in Patients With Advanced Solid Tumors With KRAS G12D Mutations

November 17, 2025 updated by: Genfleet Therapeutics (Shanghai) Inc.

An Open-Label, Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of GFH375 in Patients With KRAS G12D Mutant Advanced Solid Tumors

This is a multicenter, open-label, phase I/II study to explore the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of GFH375 in patients with advanced solid tumors harboring a KRAS G12D mutation.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

407

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 Locations

  • China
    • Anhui
      • Hefei, Anhui, China
        • Not yet recruiting
        • The First Affiliated Hospital of Anhui Medical University
        • Contact:
    • Beijing Municipality
      • Beijing, Beijing Municipality, China
        • Recruiting
        • Peking Union Medical College Hospital
        • Contact:
      • Beijing, Beijing Municipality, China
        • Recruiting
        • Cancer Hospital, Chinese Academy of Medical Sciences
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China
        • Recruiting
        • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
        • Contact:
      • Guangzhou, Guangdong, China
        • Recruiting
        • The Sixth Affiliated Hospital of Sun Yat-sen University
        • Contact:
    • Guangxi
      • Nanning, Guangxi, China
        • Not yet recruiting
        • Guangxi Medical University Cancer Hospital
        • Contact:
        • Contact:
          • Jianbo He
    • Heilongjiang
      • Haerbin, Heilongjiang, China
        • Not yet recruiting
        • Harbin medical university cancer hospital
        • Contact:
    • Henan
      • Zhengzhou, Henan, China
        • Recruiting
        • The First Affiliated Hospital of Zhengzhou University
        • Contact:
    • Hubei
      • Wuhan, Hubei, China
        • Recruiting
        • Union Hospital Tongji Medical College HuaZhong University of Science and Technology
        • Contact:
    • Hunan
      • Changsha, Hunan, China
        • Recruiting
        • Hunan Cancer hospital
        • Contact:
    • Jiangsu
      • Nanjing, Jiangsu, China
        • Recruiting
        • Jiangsu Province Hospital
        • Contact:
    • Liaoning
      • Shenyang, Liaoning, China
        • Recruiting
        • The First Affiliated Hospital of China Medical University
        • Contact:
      • Shenyang, Liaoning, China
        • Not yet recruiting
        • Liaoning Cancer Hospital & Institute
        • Contact:
    • Shandong
      • Jinan, Shandong, China
        • Recruiting
        • Shandong Cancer Hospital
        • Contact:
        • Contact:
          • Zuoxin Niu
    • Shanghai Municipality
      • Shanhai, Shanghai Municipality, China, 201210
        • Recruiting
        • Shanghai Chest Hospital
        • Contact:
    • Sichuan
      • Chengdu, Sichuan, China
        • Not yet recruiting
        • Sichuan Cancer Hospital
        • Contact:
    • Tianjing
      • Tianjing, Tianjing, China
        • Not yet recruiting
        • Tianjin Medical University Cancer Institute & Hospital
        • Contact:
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • Recruiting
        • Zhejiang Cancer Hospital
        • Contact:
      • Hangzhou, Zhejiang, China
        • Recruiting
        • The Second Affiliated Hospital Zhejiang University School of Medicine
        • Contact:
      • Hangzhou, Zhejiang, China
        • Not yet recruiting
        • The First Affiliated Hospital Zhejiang University School Of Medicine
        • Contact:

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. Subjects must voluntarily agree to participate in the trial and sign a written informed consent form.
  2. Male or female ≥ 18 years old and ≤75 years old.
  3. ECOG performance status of 0-1.
  4. With a life expectancy of ≥12 weeks.
  5. With histologically or cytologically confirmed advanced or metastatic solid tumors harboring KRAS G12D mutation.
  6. Have at least one measurable lesion according to RECIST1.1, and the phase Ia allows no measurable lesion.
  7. Adequate laboratory parameters during the screening period.

Exclusion Criteria:

  1. Active brain metastases.
  2. Prior treatment with a KRAS G12D inhibitor.
  3. Palliative radiotherapy was completed within 14 days before the first dose.
  4. Have poorly controlled or severe cardiovascular disease.
  5. Subjects with active hepatitis B or active hepatitis C.
  6. Known allergy to the study drug or its components.
  7. Pregnant or lactating women.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GFH375
Drug: GFH375
GFH375 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase Ia:The incidence and severity of AEs and SAEs
Time Frame: 24 months
The incidence and severity of AEs and SAEs
24 months
Phase Ia:The incidence of DLT events
Time Frame: 21 days
The incidence of DLT events
21 days
Phase Ib:The incidence and severity of AEs and SAEs
Time Frame: 24 months
The incidence and severity of AEs and SAEs
24 months
Phase II:Overall response rate (ORR)
Time Frame: 24 months
For NSCLC cohort： Assessed by BICR according to RECIST 1.1；For other cohorts： Assessed by investigators according to RECIST 1.1；
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma concentrations
Time Frame: up to 21 days
Plasma concentrations and PK parameters of GFH375
up to 21 days
Efficacy endpoints
Time Frame: 24 months
Duration of response (DoR)
24 months
Efficacy endpoints
Time Frame: 24 months
Disease control rate (DCR)
24 months
Efficacy endpoints
Time Frame: 24 months
Progression free survival (PFS)
24 months
Efficacy endpoints
Time Frame: 24 months
Overall survival (OS)
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: Aiping Zhou, MD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  • Principal Investigator: Shun Lu, MD, Shanghai Chest Hospital

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)

July 9, 2024

Primary Completion (Estimated)

July 31, 2028

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

July 8, 2024

First Submitted That Met QC Criteria

July 8, 2024

First Posted (Actual)

July 15, 2024

Study Record Updates

Last Update Posted (Actual)

November 20, 2025

Last Update Submitted That Met QC Criteria

November 17, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GFH375X1101

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

product manufactured in and exported from the U.S.

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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