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

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: Not yet recruiting
• Conditions: Metastatic Pancreatic Cancer
• Intervention / Treatment: Drug: GFH375; Drug: Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jin Li; Phone Number: +86 21 6882 1388; Email: jli@genfleet.com

Participation Criteria

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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

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	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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: Genfleet Therapeutics (Shanghai) Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 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 (Estimated): December 3, 2025

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Drug Administration Routes; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Enzymes and Coenzymes; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Gemcitabine; Fluorouracil; Leucovorin; Paclitaxel; Tegafur; Injections; Drug Therapy; gimeracil; potassium oxonate
• 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