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

NCT07262567 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: GFH375X1301
• Study Type: interventional
• Target: 320
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Metastatic Pancreatic Cancer

Outcome Measures

Primary Outcomes (2)

• OS

  Overall Survival

  Up to approximately 2 years

• PFS

  Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, as Determined by BICR

  Up to approximately 2 years

Secondary Outcomes (9)

• PFS

  Up to approximately 2 years

• ORR

  Up to approximately 2 years

• DCR

  Up to approximately 2 years

• DoR

  Up to approximately 2 years

• TTR

  Up to approximately 2 years

Study Arms (2)

GFH375

EXPERIMENTAL

GFH375, Oral tablets

Drug: GFH375

Chemotherapy

ACTIVE COMPARATOR

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

Interventions

GFH375 DRUG

The experimental group receives GFH375 monotherapy, QD, orally

GFH375

Chemotherapy DRUG

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.

Also known as: Irinotecan Hydrochloride Liposome Injection, Fluorouracil Injection, Calcium Folinate, Tegafur,Gimeracil and Oteracil Potassium Capsules, Gemcitabine Hydrochloride for Injection, Paclitaxel for Injection(Albumin Bound)

Chemotherapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genfleet Therapeutics (Shanghai) Inc.: lead

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Drug Therapy; Fluorouracil; Leucovorin; Tegafur; gimeracil; potassium oxonate; Gemcitabine; Injections; Paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Drug Administration Routes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Central Study Contacts

Jin Li

CONTACT

+86 21 6882 1388; jli@genfleet.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Experimental group: GFH375; Control group: investigator's choice of Chemotherapy

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 3, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: December 3, 2025

Record last verified: 2025-12