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

NCT07668752 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: GFH375X1303
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

KRAS G12D Mutation; NSCLC (Non-small Cell Lung Cancer)

Keywords

GFH375; Docetaxel; Non-small cell lung cancer (NSCLC); KRAS G12D

Outcome Measures

Primary Outcomes (3)

• 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.

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

• 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.

  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.

• Overall Survival (OS)

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

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

Secondary Outcomes (15)

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

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

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

  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.

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

  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.

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

  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.

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

  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 (2)

GFH375 group

EXPERIMENTAL

Participants will take GFH375 orally once daily of every 21-day cycle.

Drug: GFH375

Docetaxel group

ACTIVE COMPARATOR

Participants will receive docetaxel on day 1 of every 21-day cycle.

Drug: Docetaxel

Interventions

GFH375 DRUG

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

GFH375 group

Docetaxel DRUG

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

Docetaxel group

Eligibility Criteria

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

You may qualify if:

• \. Voluntary participation in the study and signed informed consent form (ICF).
• \. Age ≥ 18 years at the time of signing the ICF; male or female.
• \. Histologically or cytologically confirmed locally advanced unresectable or metastatic non small cell lung cancer (NSCLC).
• \. 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.
• \. Disease progression or intolerance to toxicity after at least one prior line of platinum based chemotherapy and anti PD 1/PD L1 antibody therapy.
• \. At least one measurable target lesion according to RECIST version 1.1.
• \. Investigator assessed life expectancy ≥ 12 weeks.
• \. Adequate organ function.
• \. Ability to communicate well, comply with scheduled follow up visits, and adhere to protocol requirements.

You may not qualify if:

• \. Presence of other driver gene mutations in NSCLC, or concurrent other KRAS or RAS mutations.
• \. Other malignancy that has progressed or required treatment within 3 years prior to randomization.
• \. Leptomeningeal metastasis, or symptomatic or progressive central nervous system (CNS) metastasis.
• \. Existing or potential severe bone injury due to bone metastasis, or uncontrolled pain related to bone metastasis.
• \. Prior treatment with KRAS G12D targeted therapy or pan RAS/KRAS targeted therapy.
• \. Prior treatment with docetaxel as part of systemic therapy.
• \. Radiotherapy within 4 weeks prior to randomization, or other local anti tumor therapy within 4 weeks prior to randomization.
• \. Other anti tumor therapy within 28 days or 5 half lives prior to randomization, or cell therapy within 3 months prior to randomization.
• \. Clinically significant severe cardiovascular disease.
• \. Stroke or other severe cerebrovascular disease within 6 months prior to randomization.
• \. Major acute or chronic infectious disease.
• \. Other poorly controlled systemic diseases.
• \. Severe psychiatric or psychological disorder, or history of drug abuse, or severe alcohol abuse.
• \. Pregnancy or breastfeeding.
• \. Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.

Sponsors & Collaborators

• Genfleet Therapeutics (Shanghai) Inc.: lead

Study Sites (1)

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, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Docetaxel

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)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Shun Lu, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Junnan Dong

CONTACT

+8615521118409; jndong@genfleet.com

Yolanda Zeng

CONTACT

+8618073129952; yaozeng@genfleet.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2026
• First Posted: June 25, 2026
• Study Start: July 15, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): April 30, 2031
• Last Updated: June 25, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)