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

NCT07259590 | Recruiting Phase 1

• 1 other identifier: GFH375X1202
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Advanced Solid Tumors Cancer; PDAC; CRC (Colorectal Cancer)

Keywords

solid tumors; KRAS G12D Mutations

Outcome Measures

Primary Outcomes (3)

• Phase Ib: Incidence of Dose-Limiting Toxicity (DLT) Events

  up to 28 days

• Phase Ib: Incidence and Severity of Adverse Events (AE) and Serious Adverse Events (SAE)

  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

  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 Outcomes (7)

• Plasma concentrations of GFH375

  up to 6 months

• Phase II: Incidence and Severity of AE and SAE

  From the first dose until 30 days after the last dose, assessed up to 24 months

• DCR

  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

  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

  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

Study Arms (2)

Arm A：GFH375 in combination with Cetuximab

EXPERIMENTAL

Arm A will enroll participants with locally advanced or metastatic solid tumors with KRAS G12D mutation.

Combination Product: GFH375

Arm B：GFH375 in combination with AG

EXPERIMENTAL

Arm B will enroll participants with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) with KRAS G12D mutation.

Combination Product: GFH375

Interventions

GFH375 COMBINATION_PRODUCT

GFH375 once daily (QD) .Cetuximab will be administered via intravenous infusion at a dose of 500 mg/m² every 2 weeks.

Also known as: Cetuximab

Arm A：GFH375 in combination with Cetuximab

Eligibility Criteria

• Age: 18 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.
• 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.
• Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors, with KRAS G12D mutation.
• Failed standard systemic treatment, or intolerant to standard treatment, or unsuitable for standard treatment, or no standard treatment available.
• At least one measurable lesions according to RECIST v1.1
• 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.
• Have sufficient organ function.

You may not qualify if:

• Symptomatic brain metastasis, leptomeningeal metastasis, spinal cord compression, or primary brain tumor.
• Presence of known coexisting other cancer driver genes.
• Previous or active history of clinically significant cardiovascular dysfunction.
• Presence of active infection.
• History of central nervous system (CNS) diseases.
• Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonitis requiring treatment.
• Newly diagnosed deep vein thrombosis or pulmonary embolism within 3 months before the first administration of the study treatment.
• Presence of uncontrolled or symptomatic pleural effusion, ascites, or pericardial effusion.
• 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.
• 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.

Sponsors & Collaborators

• Genfleet Therapeutics (Shanghai) Inc.: lead

Study Sites (4)

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

RECRUITING

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

NOT YET RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

NOT YET RECRUITING

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

NOT YET RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Taxes; Gemcitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Economics; Health Care Economics and Organizations; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Lin Shen, MD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yolanda Zeng

CONTACT

+8618073129952; yaozeng@genfleet.com

Junnan Dong

CONTACT

+8615521118409; jndong@genfleet.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: December 2, 2025
• Study Start: October 21, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)