Tests GFH375 against docetaxel in lung cancer with a KRAS G12D mutation
Compares oral GFH375 with docetaxel in adults with KRAS G12D lung cancer.
Key facts
- Who runs it
- Genfleet Therapeutics (Shanghai) Inc.
- Where
- Shanghai, ChinaSee the site
- Trial code
- Registry title
- A Study to Evaluate GFH375 Versus Docetaxel in Participants With Non-Small Cell Lung Cancer With KRAS G12D Mutation
- Status
- Recruiting
- Phase
- Phase 3
- People taking part
- 300 people, planned
- Started
- 27 Jul 2026
- Expected to end
- 30 Apr 2031
- Type of study
- Interventional, 2 groupsOne group gets an existing treatment, for comparison.
- Treatments tested
- GFH375
- Docetaxel
- Record updated
- 10 August 2026
Who can take part
AI summary
From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.
The trial is looking for adults with advanced lung cancer (non-small cell) that has the KRAS G12D mutation and got worse after earlier treatment. It compares the pill GFH375 with the chemotherapy docetaxel.
- Age
- 18 years or older
- Sex
- Men and women can join
- Disease stage
- Non-small cell lung cancer that is locally advanced and cannot be removed by surgery, or has spread. At least one tumor that can be measured on scans (RECIST version 1.1).
- Earlier treatment
- Must have had at least one earlier treatment with platinum-based chemotherapy and an anti PD-1/PD-L1 antibody therapy, and the cancer got worse or the side effects were not tolerable. Must not have had docetaxel, or KRAS G12D or pan-RAS/KRAS targeted therapy.
- Biomarker or test result
- KRAS G12D mutation, confirmed by a central laboratory on a tumor tissue sample.
Main reasons for not taking part
- Other driver gene mutations in the lung cancer, or other KRAS or RAS mutations
- Cancer in the lining of the brain and spinal cord, or brain or spinal cord metastases with symptoms or that are growing
- Another cancer that grew or needed treatment in the last 3 years
- Pregnancy or breastfeeding
- Severe heart disease, or a stroke in the last 6 months
The registry criteria, word for word
Show all 24 criteriaShow less
Who can take part
- 1. Voluntary participation in the study and signed informed consent form (ICF)
- 2. Age ≥ 18 years at the time of signing the ICF; male or female
- 3. Histologically or cytologically confirmed locally advanced unresectable or metastatic non small cell lung cancer (NSCLC)
- 4. Participants must provide adequate and qualified tumor tissue slides samples or agree to undergo tumor biopsy to obtain tissue samples for central laboratory confirmation of KRAS G12D mutation
- 5. Disease progression or intolerance to toxicity after at least one prior line of platinum based chemotherapy and anti PD 1/PD L1 antibody therapy
- 6. At least one measurable target lesion according to RECIST version 1.1
- 7. Investigator assessed life expectancy ≥ 12 weeks
- 8. Adequate organ function
- 9. Ability to communicate well, comply with scheduled follow up visits, and adhere to protocol requirements
Who cannot take part
- 1. Presence of other driver gene mutations in NSCLC, or concurrent other KRAS or RAS mutations
- 2. Other malignancy that has progressed or required treatment within 3 years prior to randomization
- 5. Prior treatment with KRAS G12D targeted therapy or pan RAS/KRAS targeted therapy
- 6. Prior treatment with docetaxel as part of systemic therapy
- 7. Radiotherapy within 4 weeks prior to randomization, or other local anti tumor therapy within 4 weeks prior to randomization
- 8. Other anti tumor therapy within 28 days or 5 half lives prior to randomization, or cell therapy within 3 months prior to randomization
- 10. Stroke or other severe cerebrovascular disease within 6 months prior to randomization
- 9. Clinically significant severe cardiovascular disease
- 11. Major acute or chronic infectious disease
- 12. Other poorly controlled systemic diseases
- 13. Severe psychiatric or psychological disorder, or history of drug abuse, or severe alcohol abuse
- 15. Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study
- 3. Leptomeningeal metastasis, or symptomatic or progressive central nervous system (CNS) metastasis
- 4. Existing or potential severe bone injury due to bone metastasis, or uncontrolled pain related to bone metastasis
- 14. Pregnancy or breastfeeding
Where in China
- Shanghai Lung Cancer Center, Shanghai Key Laboratory of Thoracic Tumor Biotherapy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of MedicineShanghai, ChinaContact: Shun Lu, MDTaking people
About the trial
What the trial wants to find out
The purpose of this study is to compare the effectiveness, safety and tolerability of GFH375 versus docetaxel in participants with KRAS G12D-mutant non-small cell lung cancer (NSCLC).
Read full original descriptionShow less
GFH375 is an oral, highly selective, non-covalent small-molecule inhibitor targeting the KRAS G12D mutation. Preclinical studies showed GFH375 strongly blocks KRAS-driven signaling and cancer cell growth, and demonstrated anti-tumor activity in NSCLC animal models. Docetaxel is a chemotherapy drug for locally advanced or metastatic NSCLC.
This is an open-label, randomized controlled trial. Both participant and study doctor will know which study medication each participant receives.
After enrollment, participant will be randomly assigned to either the GFH375 group or docetaxel group by chance. Neither participant nor study doctor can pick your treatment group. You have a two-thirds chance to receive GFH375 and a one-third chance to receive docetaxel.
* GFH375 group: Take GFH375 tablets by mouth once daily as scheduled; each treatment cycle lasts 21 days. * Docetaxel group: Receive docetaxel via intravenous infusion at 75 mg/m² once every 3 weeks.
Study treatment will continue until cancer gets worse, participant can't tolerate the study treatment, or other conditions make participant unable to keep receiving study treatment.
Some participants on docetaxel may be able to switch to GFH375 during the study if their cancer becomes worse. There will be safety checks at each visit, and the doctors will continue to check for medical problems and participant 's wellbeing throughout the study. Participants will continue to have scans of their tumor every 6 weeks for the first year, then every 9 weeks until their cancer becomes worse. After participant's cancer becomes worse, clinic staff will telephone participant every 3 mouths to check on their cancer.
The 2 groups in the trial
- GFH375 groupTreatment being tested
Participants will take GFH375 orally once daily of every 21-day cycle.
Treatment: GFH375
- Docetaxel groupExisting treatment, for comparison
Participants will receive docetaxel on day 1 of every 21-day cycle.
Treatment: Docetaxel
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Contact the study team: see the registry record → Contacts and Locations
Print a page for my doctorData and sources
- Registry record
- Listed on ClinicalTrials.gov.
- Official title
- A Phase III, Randomized, Open-Label, Multicenter Study to Evaluate GFH375 Versus Docetaxel in Participants With Locally Advanced and Unresectable or Metastatic Non-Small Cell Lung Cancer With KRAS G12D Mutation Failed Prior Standard Therapy
- Plain-language title
- Tests GFH375 against docetaxel in lung cancer with a KRAS G12D mutationGenerated from the registry record. The registry title is the official one.
- AI summary
- From the trial's eligibility criteria. Read by machine on 13 November 2026.
- Record updated
- 10 August 2026