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KRAS G12D MutationPhase 3NCT07668752

A Study to Evaluate GFH375 Versus Docetaxel in Participants With Non-Small Cell Lung Cancer With KRAS G12D Mutation

A Phase 3 study testing GFH375 and Docetaxel in people with KRAS G12D Mutation and NSCLC (Non-small Cell Lung Cancer), run by Genfleet Therapeutics (Shanghai) Inc. at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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). GFH375 is an oral, highly selective, non-covalent small-molecule inhibitor targeting the KRAS G12D mutation. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
GFH375 and Docetaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
300 participants
Where
1 siteChina
Study dates
27 Jul 2026to 30 Apr 2031
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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 join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

China1 site, 1 recruiting
  • Shanghai Lung Cancer Center, Shanghai Key Laboratory of Thoracic Tumor Biotherapy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine

    Shanghai, Shanghai Municipality, 201210

    Shun Lu, MD, 8621-22200000*5341, chestgcp@126.com

    Recruiting

Other trials in China

About this study

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

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).

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.

Read more

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.

Being tested
GFH375, Docetaxel
Keywords
GFH375, Docetaxel, Non-small cell lung cancer (NSCLC), KRAS G12D
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GFH375Drug

    GFH375 administered orally at the protocol-specified dose once daily. Each treatment cycle is 21 days.

  • DocetaxelDrug

    Receive docetaxel via intravenous infusion at 75 mg/m² once every 3 weeks.

Study groups in NCT07668752
Study groupRoleWhat they receive
GFH375 groupExperimentalParticipants will take GFH375 orally once daily of every 21-day cycle.
Receives: Drug: GFH375
Docetaxel groupActive comparatorParticipants will receive docetaxel on day 1 of every 21-day cycle.
Receives: Drug: Docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate(ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. as assessed by blinded independent central review (BICR)

    ORR is the proportion of participants whose best response is either complete response (CR) or partial response (PR) per RECIST v1.1 assessed by BICR.

    Measured: From the first dose until the date of first documented CR or PR, assessed up to 24 months

  2. Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. as assessed by blinded independent central review (BICR)

    PFS is defined as the time from the date of randomization until the date of documented radiographic disease progression per RECIST v1.1, as assessed by BICR or until death due to any cause, whichever comes first.

    Measured: 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.

  3. Overall Survival (OS)

    OS is defined as the time from the date of randomization until the date of death from any cause.

    Measured: From the first dose until the date of death from any cause, whichever came first, assessed up to 36~48 months

Secondary outcomes (15)
  1. Objective Response Rate (ORR) per RECIST v1.1, as assessed by the investigator

    ORR is defined as the proportion of participants whose best overall response (BOR) is rated as confirmed complete response (CR) or confirmed partial response (PR) per RECIST v1.1. as assessed by the investigator.

    Measured: From the first dose until the date of first documented CR or PR,assessed up to 24 months.

  2. PFS per RECIST v1.1. as assessed by the investigator

    PFS is defined as the time from the date of randomization until the date of documented radiographic disease progression per RECIST v1.1 as assessed by the investigator or until death due to any cause, whichever comes first.

    Measured: 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.

  3. DCR per RECIST v 1.1 as assessed by the investigator and the BICR

    DCR is defined as the proportion of participants whose best overall response is rated as CR, confirmed PR or SD per RECIST v1.1 as assessed by the investigator and the BICR.

    Measured: 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.

  4. DoR per RECIST v 1.1 as assessed by the investigator and the BICR

    DOR is defined as the time from the date of first documented response (CR or PR subsequently confirmed) to the date of first documented PD per RECIST v1.1 as assessed by the investigator and the BICR or death due to any cause, whichever occurs first.

    Measured: 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.

  5. TTR per RECIST v 1.1 as assessed by the investigator and the BICR

    TTR is defined as the time from the date of randomization to the first documentation of objective response (confirmed CR or confirmed PR) per RECIST v1.1. as assessed by the investigator and the BICR.

    Measured: 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.

  6. Number of Participants with Adverse Events (AEs)

    An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

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

  7. Severity of Adverse Events(AEs)

    The severity of an adverse event is commonly graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE )5.0.

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

  8. Incidence of AEs that result in treatment discontinuation, treatment interruption, or dose reduction.

    AEs that result in treatment discontinuation, treatment interruption, or dose reduction.

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

  9. Severity of adverse events (AEs) leading to treatment discontinuation, treatment interruption, and dose reduction.

    Severity of adverse events (AEs) leading to treatment discontinuation, treatment interruption, and dose reduction per CTCAE 5.0.

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

  10. Time to deterioration in NSCLC symptoms evaluated via European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) items

    Time to deterioration is defined as time between randomization and the first occurrence of a meaningful deterioration in the corresponding EORTC QLQ-LC13 items score compared with the baseline score. EORTC QLQ-LC13 is a lung-cancer specific module that serves as an additional 13 item questionnaire to the general EORTC cancer questionnaire. It consists of 3 items to assess dyspnea, and 10 single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. Scores range from 0 to 100. A high score for a symptom scale/item represents a high level of symptomatology/problems.

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

  11. Time to Worsening measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) items

    Time to Worsening is defined as time between randomization and the first occurrence of a meaningful worsening in the composite EORTC QLQ-C30 items scores compared with the baseline score. EORTC-QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." For functional scales, higher scores indicate better functioning, while for symptom scales/items, higher scores indicate worse symptoms.

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

  12. Change from baseline in EORTC QLQ-C30

    The EORTC-QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." For functional scales, higher scores indicate better functioning, while for symptom scales/items, higher scores indicate worse symptoms.

    Measured: From the first dose to week12.

  13. Change from baseline in EORTC QLQ-LC13

    EORTC QLQ-LC13 is a lung-cancer specific module that serves as an additional 13 item questionnaire to the general EORTC cancer questionnaire. It consists of 3 items to assess dyspnea, and 10 single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. Scores range from 0 to 100. A high score for a symptom scale/item represents a high level of symptomatology/problems.

    Measured: From the first dose to week12.

  14. Pharmacokinetics (PK) of GFH375: Trough concentration after multiple dosing

    Trough concentration will be recorded from plasma samples collected.

    Measured: From the first dose to Cycle 6 Day 1(each cycle is 21 days).

  15. PK of GFH375: Peak concentration after multiple dosing

    Peak concentration will be recorded from plasma samples collected.

    Measured: From the first dose to Cycle 6 Day 1(each cycle is 21 days).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2026
  2. Study start27 Jul 2026
  3. Primary completion30 Jun 2030 (estimated)
  4. Study completion30 Apr 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07668752
Sponsor's protocol ID
GFH375X1303
Status last verified
Aug 2026
First submitted
15 Jun 2026
Last updated
10 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing GFH375 and Docetaxel in people with KRAS G12D Mutation and NSCLC (Non-small Cell Lung Cancer), run by Genfleet Therapeutics (Shanghai) Inc. at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Junnan Dong (+8615521118409, jndong@genfleet.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate(ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. as assessed by blinded independent central review (BICR) (time frame: From the first dose until the date of first documented CR or PR, assessed up to 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2026.

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