GFH375 vs. Docetaxel for KRAS G12D-mutant NSCLC

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a Phase 3, open-label, randomized trial comparing an oral KRAS G12D inhibitor, GFH375, with the chemotherapy drug docetaxel in adults with locally advanced or metastatic NSCLC harboring the KRAS G12D mutation. Participants are assigned by chance to receive GFH375 or docetaxel, with a two-thirds to one-third allocation in favor of GFH375. The trial includes patients who have progressed after platinum-based chemotherapy and PD-1/PD-L1 therapy, require measurable disease, and have adequate organ function. Key assessments include safety, tolerability, and tumor response per RECIST v1.1, with central confirmation of KRAS G12D status. The study is conducted across multiple Shanghai-based centers under Genfleet Therapeutics as lead sponsor.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* 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.
* 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.
* 9\. Clinically significant severe cardiovascular disease.
* 10\. Stroke or other severe cerebrovascular disease within 6 months prior to randomization.
* 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.
* 14\. Pregnancy or breastfeeding.
* 15\. Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.

Where it's running

• Shanghai Lung Cancer Center, Shanghai Key Laboratory of Thoracic Tumor Biotherapy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine
  Shanghai, Shanghai Municipality, China Recruiting

Study contacts

• Principal investigator: Shun Lu, MD — Shanghai Lung Cancer Center, Shanghai Key Laboratory of Thoracic Tumor Biotherapy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine
• Study coordinator: Junnan Dong
• Email: jndong@genfleet.com
• Phone: +8615521118409

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Investigating KQB365 for treating advanced solid tumors

  This study tests if a new treatment called KQB365, alone or with another drug, can help adults with advanced solid tumors that have specific genetic mutations.

  Recruiting at 11 sites Phase 1 Kumquat Biosciences Inc. · Phoenix, Arizona and 10 other locations · NCT06720987

• TS-104: a first-in-human, dose-escalation study for advanced solid tumors

  This study tests TS-104, a peptide-drug conjugate, as a single therapy in adults with advanced solid tumors like NSCLC, HNSCC, esophageal, gastric, ovarian, or endometrial cancer to see if it is safe and tolerable and whether it shows any benefit.

  Recruiting at 3 sites Phase 1 TwoStep Therapeutics, Inc. · Maumee, Ohio and 2 other locations · NCT07814248

• Icotinib after surgery for early EGFR-mutant NSCLC

  This study tests whether giving icotinib after surgery helps patients with early-stage EGFR-mutant NSCLC compare to just following them after surgery.

  Recruiting at 2 sites Betta Pharmaceuticals Co., Ltd. · Beijing, Beijing Municipality and 1 other locations · NCT07806604

• Oral Paclitaxel with Immunotherapy and SBRT as Neoadjuvant Treatment for Older Adults with NSCLC

  This trial tests a new, lighter neoadjuvant therapy that combines an oral paclitaxel solution, an immune checkpoint inhibitor, and SBRT for adults aged 70 and older with resectable NSCLC to see if it can shrink tumors before surgery.

  Recruiting Phase 4 Shanghai Pulmonary Hospital, Shanghai, China · Guangzhou, Guangdong and 4 other locations · NCT07754812

• Targeted Induction Therapy for Stage III Unresectable EGFR Mutant NSCLC

  This trial tests a targeted induction approach using fumetinib with platinum-based chemotherapy and concurrent radiochemotherapy in adults with unresectable stage III EGFR-mutant NSCLC to see if this combo can improve outcomes before possible surgery.

  Recruiting Phase 2 Shanghai Pulmonary Hospital, Shanghai, China · Shanghai, Shanghai Municipality · NCT07742332

• Pralsetinib Drug Interaction Study in RET Fusion/MUTATION Positive Solid Tumors

  This trial tests whether pralsetinib changes how the body processes certain medicines in adults with RET fusion- or mutation-positive advanced solid tumors.

  Recruiting at 2 sites Phase 4 Rigel Pharmaceuticals · Logroño, La Rioja and 1 other locations · NCT07704658

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.