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

GenFleet Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Combination Product: GFH375

Study type: Interventional

Funder types: Industry

Identifiers

NCT07259590

GFH375X1202

Details and patient eligibility

About

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.

Enrollment: 126 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Voluntarily participate in the study and sign the informed consent form.
2. 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.
3. Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors, with KRAS G12D mutation.
4. Failed standard systemic treatment, or intolerant to standard treatment, or unsuitable for standard treatment, or no standard treatment available.
5. At least one measurable lesions according to RECIST v1.1
6. 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.
7. Have sufficient organ function.

Exclusion criteria

1. Symptomatic brain metastasis, leptomeningeal metastasis, spinal cord compression, or primary brain tumor.
2. Presence of known coexisting other cancer driver genes.
3. Previous or active history of clinically significant cardiovascular dysfunction.
4. Presence of active infection.
5. History of central nervous system (CNS) diseases.
6. Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonitis requiring treatment.
7. Newly diagnosed deep vein thrombosis or pulmonary embolism within 3 months before the first administration of the study treatment.
8. Presence of uncontrolled or symptomatic pleural effusion, ascites, or pericardial effusion.
9. 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.
10. 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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126 participants in 2 patient groups

Arm A：GFH375 in combination with Cetuximab

Experimental group

Description:

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

Treatment:

Combination Product: GFH375

Combination Product: GFH375

Arm B：GFH375 in combination with AG

Experimental group

Description:

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

Treatment:

Combination Product: GFH375

Combination Product: GFH375