RAS MutationPhase 1/2GFH276X1203NCT07846358
This is a Multicenter, Open-label, Phase I/II Study to Explore the Safety, Tolerability, Pharmacokinetics (PK), and Preliminary Efficacy of GFH276 in Patients With Advanced NSCLC Harboring a RAS Mutation.
A Phase 1/2 study testing GFH276, with or without Tislelizumab and Pemetrexed in people with RAS Mutation and Non-small Cell Lung Cancer (NSCLC), run by Genfleet Therapeutics (Shanghai) Inc..
Trial summary
This is an open-label, multicenter Phase Ib/II clinical study evaluating GFH276 in combination with tislelizumab plus pemetrexed/platinum based regimen as first-line therapy in participants with locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC) harboring RAS mutation or KRAS amplification. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- RAS Mutation, Non-small Cell Lung Cancer (NSCLC)
- What is being tested?
- GFH276, with or without Tislelizumab and Pemetrexed
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- No sites listed yet
- Study dates
- Nov 2026to Dec 2028
- Phase
- Phase 1/2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically/cytologically confirmed locally advanced or metastatic non squamous NSCLC (AJCC 8th edition Stage IIIB-IV).
- Confirmed RAS mutation or KRAS amplification；tumor cell PD L1 test report available
- No prior systemic anti-tumor therapy for advanced disease
- At least 1 measurable lesion outside the central nervous system (CNS) per RECIST v1.1
- ECOG performance status 0 or 1
- Life expectancy>3 months
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- Willing to provide written informed consent
- Fertile participants must use effective contraception
- Adequate organ function
Who cannot join
- Other active malignancy within 3 years
- Symptomatic brain metastases, leptomeningeal disease, spinal cord compression, or primary brain tumor
- History of active clinically significant cardiovascular dysfunction
- Known to harbor other targetable driver gene alterations
- Presence of active infection (HIV, HBV, HCV,)
- Prior anti-tumor therapy within 28 days or 5 half-lives
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- Diagnosis of unstable thrombotic events requiring therapeutic intervention within 3 months prior to the first dose of study treatment.
- Hypersensitivity to study drugs, or inability to swallow tablets or comply with study procedures.
- History of central nervous system (CNS)disease
- Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonia that requires treatment.
- With uncontrollable or symptomatic pleural effusion, ascites, or pericardial effusion.
- Active autoimmune disease requiring systemic treatment.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Phase Ib/II, Multicenter, Open-Label Study To Evaluate Safety, Efficacy And Pharmacokinetics Of GFH276 In Combination With Tislelizumab, Pemetrexed And Platinum (Carboplatin Or Cisplatin) As First-Line Therapy In Participants With Locally Advanced Or Metastatic Non-Squamous Non-Small-Cell Lung Cancer Harboring RAS Mutation
This is an open-label, multicenter Phase Ib/II clinical study evaluating GFH276 in combination with tislelizumab plus pemetrexed/platinum based regimen as first-line therapy in participants with locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC) harboring RAS mutation or KRAS amplification.
Read the detailed description
This open-label, multicenter Phase Ib/II study enrolls participants with locally advanced or metastatic non-squamous NSCLC with RAS mutation or KRAS amplification, who have not received prior systemic anti-cancer therapy for advanced disease.
In Phase Ib, dose escalation of GFH276 will be performed in assigned arm to identify the recommended Phase 2 dose (RP2D) based on dose-limiting toxicity (DLT) and the overall safety profile. After RP2D determination, participants will be enrolled in Phase II to further evaluate the anti-tumor efficacy and long-term safety of each combination regimen. Study-related assessments will include tumor imaging, laboratory tests, adverse event monitoring, and pharmacokinetic sampling throughout the treatment period.
Participants will continue their assigned study treatment until confirmed disease progression, intolerable toxicity, withdrawal of consent, or study closure.
- Conditions
- RAS Mutation, Non-small Cell Lung Cancer (NSCLC)
- Being tested
- GFH276, with or without Tislelizumab, Pemetrexed, Cisplatin, Carboplatin
- Keywords
- GFH276, RAS Mutation, Non-small cell lung cancer (NSCLC)
- 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.
GFH276Drug
Oral GFH276, administered at specified dose on schedule.
with or without TislelizumabDrug
Tislelizumab 200 mg, intravenous infusion, once every 3 weeks.or without Tislelizumab
PemetrexedDrug
Pemetrexed 500 mg/m², intravenous infusion, once every 3 weeks.
CisplatinDrug
Cisplatin 75 mg/m², intravenous infusion, once every 3 weeks.
CarboplatinDrug
Carboplatin at AUC=5, intravenous infusion, once every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| GFH276 ±Tislelizumab + AP | Experimental | GFH276 once daily; Tislelizumab 200 mg, IV; AP: Pemetrexed 500 mg/m², IV; Cisplatin/Carboplatin 75 mg/m²/AUC=5, IV, every 3 weeks Receives: Drug: GFH276; Drug: with or without Tislelizumab; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events
The incidence of DLT events
Measured: First 21 days
Phase II:Objective Response Rate (ORR)
Assessed by investigators according to RECIST 1.1
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 36 months
Phase Ib:Incidence and Severity of Adverse Events (AE) and Serious Adverse Events (SAE)
The incidence and severity of AEs and SAEs，according to NCI CTCAE，v6.0
Measured: From the first dose until 30 days after the last dose, assessed up to 36 months
Secondary outcomes (6)
DCR
Disease Control Rate (DCR)
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 36 months
DoR
Duration of Response assessed by investigators
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 36 months
TTR
Time To Response assessed by investigators
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 36 months
PFS
Progression-Free Survival (PFS) per Response Evaluation Criteria according to RECIST 1.1, as Determined by investigators
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 36 months
OS
Overall Survival
Measured: From the first dose until date of death from any cause, assessed up to 36 months
Phase II: Incidence and Severity of AE and SAE
Incidence and Severity of AE and SAE，Assessed according to CTCAE 6.0
Measured: From the first dose until 30 days after the last dose, assessed up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2026
- Study startNov 2026 (estimated)
- Primary completionDec 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RAS MutationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Genfleet Therapeutics (Shanghai) Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ziming Li, MD, Principal investigator, Shanghai Chest Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07846358
- Sponsor's protocol ID
- GFH276X1203
- Acronym
- GFH276X1203
- Status last verified
- Sep 2026
- First submitted
- 22 Sep 2026
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II, Multicenter, Open-Label Study To Evaluate Safety, Efficacy And Pharmacokinetics Of GFH276 In Combination With Tislelizumab, Pemetrexed And Platinum (Carboplatin Or Cisplatin) As First-Line Therapy In Participants With Locally Advanced Or Metastatic Non-Squamous Non-Small-Cell Lung Cancer Harboring RAS Mutation
- ClinicalTrials.gov ID
- NCT07846358
- Acronym / sponsor ID
- GFH276X1203 / GFH276X1203
- Conditions
- RAS Mutation, Non-small Cell Lung Cancer (NSCLC)
- Keywords
- GFH276, RAS Mutation, Non-small cell lung cancer (NSCLC)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 84 participants (estimated)
- Lead sponsor
- Genfleet Therapeutics (Shanghai) Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2026 (estimated)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 29 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, multicenter Phase Ib/II clinical study evaluating GFH276 in combination with tislelizumab plus pemetrexed/platinum based regimen as first-line therapy in participants with locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC) harboring RAS mutation or KRAS amplification.
Detailed description
This open-label, multicenter Phase Ib/II study enrolls participants with locally advanced or metastatic non-squamous NSCLC with RAS mutation or KRAS amplification, who have not received prior systemic anti-cancer therapy for advanced disease.
In Phase Ib, dose escalation of GFH276 will be performed in assigned arm to identify the recommended Phase 2 dose (RP2D) based on dose-limiting toxicity (DLT) and the overall safety profile. After RP2D determination, participants will be enrolled in Phase II to further evaluate the anti-tumor efficacy and long-term safety of each combination regimen. Study-related assessments will include tumor imaging, laboratory tests, adverse event monitoring, and pharmacokinetic sampling throughout the treatment period.
Participants will continue their assigned study treatment until confirmed disease progression, intolerable toxicity, withdrawal of consent, or study closure.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GFH276 ±Tislelizumab + AP | Experimental | Drug: GFH276, Drug: with or without Tislelizumab, Drug: Pemetrexed, Drug: Cisplatin, Drug: CarboplatinGFH276 once daily; Tislelizumab 200 mg, IV; AP: Pemetrexed 500 mg/m², IV; Cisplatin/Carboplatin 75 mg/m²/AUC=5, IV, every 3 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically/cytologically confirmed locally advanced or metastatic non squamous NSCLC (AJCC 8th edition Stage IIIB-IV).
- Confirmed RAS mutation or KRAS amplification；tumor cell PD L1 test report available
- No prior systemic anti-tumor therapy for advanced disease
- At least 1 measurable lesion outside the central nervous system (CNS) per RECIST v1.1
- ECOG performance status 0 or 1
Key exclusion criteria (12 listed)
- Other active malignancy within 3 years
- Symptomatic brain metastases, leptomeningeal disease, spinal cord compression, or primary brain tumor
- History of active clinically significant cardiovascular dysfunction
- Known to harbor other targetable driver gene alterations
- Presence of active infection (HIV, HBV, HCV,)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GFH276Oral GFH276, administered at specified dose on schedule. | Drug | GFH276 ±Tislelizumab + AP |
| with or without TislelizumabTislelizumab 200 mg, intravenous infusion, once every 3 weeks.or without Tislelizumab | Drug | GFH276 ±Tislelizumab + AP |
| PemetrexedPemetrexed 500 mg/m², intravenous infusion, once every 3 weeks. | Drug | GFH276 ±Tislelizumab + AP |
| CisplatinCisplatin 75 mg/m², intravenous infusion, once every 3 weeks. | Drug | GFH276 ±Tislelizumab + AP |
| CarboplatinCarboplatin at AUC=5, intravenous infusion, once every 3 weeks. | Drug | GFH276 ±Tislelizumab + AP |
Primary outcome
Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events
Time frame: First 21 days
The incidence of DLT events
Phase II:Objective Response Rate (ORR)
Time frame: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Assessed by investigators according to RECIST 1.1
Phase Ib:Incidence and Severity of Adverse Events (AE) and Serious Adverse Events (SAE)
Time frame: From the first dose until 30 days after the last dose, assessed up to 36 months
The incidence and severity of AEs and SAEs，according to NCI CTCAE，v6.0
6 secondary outcomes
DCR
Time frame: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
DoR
Time frame: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
TTR
Time frame: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
PFS
Time frame: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
OS
Time frame: From the first dose until date of death from any cause, assessed up to 36 months
Phase II: Incidence and Severity of AE and SAE
Time frame: From the first dose until 30 days after the last dose, assessed up to 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2026.
- Individual participant dataSharing planned: No
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RecruitingPhase 3
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RecruitingPhase 1/2
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ziming Li, MD principal investigator
Shanghai Chest Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing GFH276, with or without Tislelizumab and Pemetrexed in people with RAS Mutation and Non-small Cell Lung Cancer (NSCLC), run by Genfleet Therapeutics (Shanghai) Inc..
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 12 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: opening soon, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Li Bai (+86 2168821388, lbai@genfleet.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events (time frame: First 21 days). 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 29 Sep 2026.