Phase III Study to Compare GFH375 and Chemotherapy in Patients With KRAS G12D-Mutant Metastatic Pancreatic Cancer

August 13, 2026 updated by: Genfleet Therapeutics (Shanghai) Inc.

A Multicenter, Open-Label, Randomized Controlled Phase III Study to Compare the Efficacy and Safety/Tolerability of GFH375 Monotherapy Versus Investigator's Choice of Chemotherapy in Patients With Previously Treated KRAS G12D-Mutant Metastatic Pancreatic Cancer

This study plans to enroll participants with previously treated metastatic pancreatic cancer and harbor centrally confirmed KRAS G12D mutation. These participants are required to experience disease progression on or after at least one prior standard systemic therapy containing fluorouracil or gemcitabine, and either progressed on or were intolerant to the last treatment. Eligible participants will be randomized 1:1 to the experimental group or the control group for treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

320

Phase

  • Phase 3

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
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100142
        • Recruiting
        • Peking University Cancer Hospital & Institute
        • Contact:
          • Lin Shen
        • Principal Investigator:
          • Lin Shen, Ph D

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:

  • Voluntarily participate in the study and sign the informed consent form.
  • Male or female aged 18-80 years (inclusive) at the time of signing the informed consent form.
  • Pathologically confirmed pancreatic cancer (derived from pancreatic ductal epithelium) at metastatic stage.
  • Have received at least one prior standard systemic therapy.
  • Participants must have at least one measurable lesion (per RECIST 1.1 criteria).
  • Expected survival time ≥ 12 weeks as judged by the investigator.
  • Have adequate organ function

Exclusion Criteria:

  • Other malignant tumors that progressed or required treatment within 3 years prior to randomization.
  • With active central nervous system (CNS) metastasis.
  • Previous receipt of therapy targeted for KRAS G12D or pan-RAS/KRAS.
  • Received radiotherapy within 4 weeks prior to randomization or other local anti-tumor therapy within 4 weeks prior to randomization.
  • Received other anti-tumor therapy within 28 days or 5 half-lives (whichever is shorter) prior to randomization.
  • With clinically significant severe cardiovascular diseases.
  • Stroke or other severe cerebrovascular diseases within 6 months prior to randomization.
  • Complicated with major acute or chronic infectious diseases.
  • Have severe mental or psychological diseases, or a history of drug abuse or severe alcoholism.
  • Pregnant or lactating females.
  • Other conditions deemed inappropriate for participation in the study by the investigator.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GFH375
GFH375, Oral tablets
Drug: GFH375
The experimental group receives GFH375 monotherapy, QD, orally
Active Comparator: Chemotherapy
There are three chemotherapy regimens. If participants are randomized to the control group, they will receive the treatment as determined by the investigator.
Drug: Chemotherapy
The control group includes three treatment regimens: AG, nal-IRI + 5-FU/LV, and S-1. If participants are randomized to the control group, they will receive the treatment which is determined by the investigator.
Other Names:
  • Calcium Folinate
  • Gemcitabine Hydrochloride for Injection
  • Tegafur,Gimeracil and Oteracil Potassium Capsules
  • Paclitaxel for Injection(Albumin Bound)
  • Irinotecan Hydrochloride Liposome Injection
  • Fluorouracil Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
OS
Time Frame: Up to approximately 2 years
Overall Survival
Up to approximately 2 years
PFS
Time Frame: Up to approximately 2 years
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, as Determined by BICR
Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS
Time Frame: Up to approximately 2 years
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, as Determined by investagors
Up to approximately 2 years
ORR
Time Frame: Up to approximately 2 years
ORR assessed by investigators and BICR
Up to approximately 2 years
DCR
Time Frame: Up to approximately 2 years
DCRassessed by investigators and BICR
Up to approximately 2 years
DoR
Time Frame: Up to approximately 2 years
DoR assessed by investigators and BICR
Up to approximately 2 years
TTR
Time Frame: Up to approximately 2 years
TTR assessed by investigators and BICR
Up to approximately 2 years
The incidence and severity of AEs and SAEs
Time Frame: Up to approximately 2 years
The incidence and severity of AEs and SAEs
Up to approximately 2 years
EORTC QLQ-C30 Score
Time Frame: Up to approximately 2 years
Changes in EORTC QLQ-C30
Up to approximately 2 years
EORTC QLQ-PAN26 Score
Time Frame: Up to approximately 2 years
Changes in EORTC QLQ-PAN26 Scores
Up to approximately 2 years
Plasma concentrations of GFH375
Time Frame: Up to approximately 2 years
Plasma concentrations of GFH375
Up to approximately 2 years

Collaborators and Investigators

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

Sponsor

Genfleet Therapeutics (Shanghai) Inc.

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)

December 4, 2025

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

June 1, 2028

Study Registration Dates

First Submitted

November 20, 2025

First Submitted That Met QC Criteria

December 1, 2025

First Posted (Actual)

December 3, 2025

Study Record Updates

Last Update Posted (Actual)

August 14, 2026

Last Update Submitted That Met QC Criteria

August 13, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GFH375X1301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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