GFH375 Monotherapy and Combination Therapy as First-Line Treatment for Advanced KRAS G12D-Mutant Non-Small Cell Lung Cancer

NCT07554859 | Not Yet Recruiting Phase 2

• 1 other identifier: GFH375X1302
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a multicenter, open-label, randomized clinical trial aimed at exploring the efficacy and safety of three treatment regimens for treatment-naive advanced NSCLC patients with KRAS G12D mutation: GFH375 monotherapy (Cohort 1), GFH375 combined with cetuximab (Cohort 2), and GFH375 combined with pemetrexed (Cohort 3).Every cohort will recruit 30 participants.

Conditions

NSCLC (Advanced Non-small Cell Lung Cancer)

Keywords

KRAS G12D Mutations

Outcome Measures

Primary Outcomes (1)

• the efficacy of GFH375 as monotherapy and in combination therapy

  Objective response rate (ORR) assessed by RECIST 1.1 according to researchers

  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 (3)

Arm A:GFH375

EXPERIMENTAL

Arm A :will enroll participants with previously untreated advanced NSCLC harboring KRAS G12D mutations.

Drug: ArmA:GFH375

Arm B:GFH375 in combination with Cetuximab

EXPERIMENTAL

Arm B will enroll participants with previously untreated advanced NSCLC harboring KRAS G12D mutations.

Drug: Arm B:GFH375

Arm C:GFH375 in combination with Pemetrexed

EXPERIMENTAL

Arm C will enroll participants with previously untreated advanced NSCLC harboring KRAS G12D mutations.

Drug: Arm C:GFH375

Interventions

ArmA:GFH375 DRUG

GFH375 once daily (QD) 28 days as a cycle.

Also known as: GFH375

Arm A:GFH375

Arm B:GFH375 DRUG

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 B:GFH375 in combination with Cetuximab

Arm C:GFH375 DRUG

GFH375 once daily (QD) .Pemetrexed disodium will be administered via intravenous infusion at a dose of 500 mg/m² every 3 weeks.

Also known as: Pemetrexed disodium

Arm C:GFH375 in combination with Pemetrexed

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily agree to participate in this study and sign the written informed consent form.
• Male or female, aged 18 to 75 years at the time of signing the informed consent form.
• Pathologically (histologically or cytologically) confirmed advanced (Stage IV) or locally advanced non-squamous non-small cell lung cancer that is not amenable to radical surgery or radiotherapy.
• Have a written report confirming KRAS G12D mutation positive.
• Able to provide an archival tumor tissue sample \[formalin-fixed, paraffin-embedded (FFPE) block or unstained FFPE tumor sections\] or to undergo a tumor biopsy prior to treatment.
• No prior systemic anti-tumor therapy for advanced disease; or not eligible for standard of care therapy; or in the investigator's judgment, may benefit more from GFH375 monotherapy or combination therapy than from available standard therapy.
• Have at least one measurable lesion outside the central nervous system (CNS) per RECIST v1.1. Lesions that have received prior local radiotherapy can be considered measurable only if they have demonstrated clear progression after radiotherapy; otherwise, they are not considered measurable.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
• Life expectancy of at least 3 months as assessed by the investigator. 10.Adequate organ function.

You may not qualify if:

• Has had another invasive malignancy that progressed or required treatment within 3 years prior to randomization, except adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, squamous cell carcinoma in situ, superficial bladder cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, or papillary thyroid carcinoma.
• Pathologically (histologically or cytologically) confirmed squamous cell lung cancer, adenosquamous carcinoma, neuroendocrine carcinoma (including small cell lung cancer and large cell neuroendocrine carcinoma), or mixed small cell lung cancer.
• Known to harbor other targetable driver gene alterations.
• Has active or symptomatic brain metastases, leptomeningeal metastases, or spinal cord compression.
• Has clinically significant severe cardiovascular disease.
• Has had a stroke or other serious cerebrovascular event within 6 months prior to randomization.
• Has a history of deep vein thrombosis or other severe thromboembolism within 3 months prior to randomization.
• Has pleural effusion, ascites, or pericardial effusion requiring frequent drainage (≥2 times per month) or associated with moderate to severe symptoms.
• Has clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonitis requiring treatment.
• At high risk of gastrointestinal bleeding or perforation.
• Has pyloric obstruction, persistent or recurrent vomiting (≥3 episodes within 24 hours); is unable or unwilling to swallow tablets; or has other impaired gastrointestinal function or gastrointestinal disease that may significantly affect the absorption of GFH375.
• History of chronic diarrhea.
• Has a major acute or chronic infectious disease.
• Has other uncontrolled systemic medical conditions.
• Planned major surgery as determined by the investigator.

Sponsors & Collaborators

• Genfleet Therapeutics (Shanghai) Inc.: lead

Study Sites (2)

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, China

Location

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Cetuximab; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Yilong Wu

  Guangdong Provincial People's Hospital

  STUDY CHAIR

Central Study Contacts

Yolanda Zeng

CONTACT

+8618073129952; yaozeng@genfleet.com

Dandan Li

CONTACT

+8615357948985; ddli@genfleet.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: April 28, 2026
• Study Start (Estimated): May 20, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2028
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)