KRAS G12D MutationsPhase 1/2NCT06500676
A Study of GFH375 in Patients With Advanced Solid Tumors With KRAS G12D Mutations
A Phase 1/2 study testing GFH375 in people with KRAS G12D Mutations and Advanced Solid Tumors, run by Genfleet Therapeutics (Shanghai) Inc. at 20 sites in China.
Trial summary
This is a multicenter, open-label, phase I/II study to explore the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of GFH375 in patients with advanced solid tumors harboring a KRAS G12D mutation. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- KRAS G12D Mutations, Advanced Solid Tumors
- What is being tested?
- GFH375
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 407 participants
- Where
- 20 sitesChina
- Study dates
- 9 Jul 2024to 31 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
- Subjects must voluntarily agree to participate in the trial and sign a written informed consent form.
- Male or female ≥ 18 years old and ≤75 years old.
- ECOG performance status of 0-1.
- With a life expectancy of ≥12 weeks.
- With histologically or cytologically confirmed advanced or metastatic solid tumors harboring KRAS G12D mutation.
- Have at least one measurable lesion according to RECIST1.1, and the phase Ia allows no measurable lesion.
- Adequate laboratory parameters during the screening period.
Who cannot join
- Active brain metastases.
- Prior treatment with a KRAS G12D inhibitor.
- Palliative radiotherapy was completed within 14 days before the first dose.
- Have poorly controlled or severe cardiovascular disease.
- Subjects with active hepatitis B or active hepatitis C.
- Known allergy to the study drug or its components.
- Pregnant or lactating women.
Trial locations and contacts
20 sites in 1 country. Contact the study team or a site near you to ask about taking part.
20 sites in 1 country
China20 sites, 20 recruiting
- Recruiting
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality
Aiping Zhou, 8610-87788495, zhouap1825@126.com
- Recruiting
Peking Union Medical College Hospital
Beijing, Beijing Municipality
Haitao Zhao, 8610-69154186, pumchzht@aliyun.com
- Recruiting
Hunan Cancer Hospital
Changsha, Hunan
Lin Wu, MD, 86731-89762695, wulin@hnca.org.cn
- Not yet recruiting
Sichuan Cancer Hospital
Chengdu, Sichuan
Wenxiu Yao, 8628-85420681, ywxhlx@sina.com
- Recruiting
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong
Zhihua Li, 8620-81332587, lzhdoct@163.com
- Recruiting
The Sixth Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong
Yanhong Deng, 8620-38379764, zslyllb@mail.sysu.edu.cn
- Not yet recruiting
Harbin Medical University Cancer Hospital
Haerbin, Heilongjiang
zhiwei li, MD, 0451-86298295, hydsyll@163.com
- Not yet recruiting
The First Affiliated Hospital Zhejiang University School of Medicine
Hangzhou, Zhejiang
haiping jiang, MD, 0571-87236685, jianghaiping75@163.com
- Recruiting
The Second Affiliated Hospital Zhejiang University School of Medicine
Hangzhou, Zhejiang
Ying Yuan, 86571-87783759, yuanying1999@zju.edu.cn
- Recruiting
Zhejiang Cancer Hospital
Hangzhou, Zhejiang
Zhengbo Song, 86571-88122146, irb@zjcc.org.cn
- Not yet recruiting
The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui
Yingying Du, 0551-62922017, duyingying@126.com
- Recruiting
Shandong Cancer Hospital
Jinan, Shandong
Yuping Sun, 86531-67626929, 13370582181@163.com
Zuoxin Niu
- Recruiting
Jiangsu Province Hospital
Nanjing, Jiangsu
Lingjun Zhu, 8625-68306360, 13951807457@139.com
- Not yet recruiting
Guangxi Medical University Cancer Hospital
Nanning, Guangxi
Qitao Yu, 86771-5323064, yqt178@163.com
jianbo he
- Recruiting
Shanghai Chest Hospital
Shanhai, Shanghai Municipality, 201210
Shun Lu, MD, 8621-22200000*5341, chestgcp@126.com
- Not yet recruiting
Liaoning Cancer Hospital & Institute
Shenyang, Liaoning
Jingdong Zhang, MD, 024-81916632, 13804027878@163.com
- Recruiting
The First Affiliated Hospital of China Medical University
Shenyang, Liaoning
Xiujuan Qu, 8624-83282802, ydyyllwyh2010@163.com
- Not yet recruiting
Tianjin Medical University Cancer Institute & Hospital
Tianjing, Tianjing
Peng Cheng, 8622-23340123-6417, ec_tjcih@126.com
- Recruiting
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan, Hubei
Heshui Wu, 8627-85726375, whunionlunli@126.com
- Recruiting
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan
Hong Zong, 86371-66295219, tianli_llzl@163.com
About this study
Official title: An Open-Label, Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of GFH375 in Patients With KRAS G12D Mutant Advanced Solid Tumors
This is a multicenter, open-label, phase I/II study to explore the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of GFH375 in patients with advanced solid tumors harboring a KRAS G12D mutation.
- Conditions
- KRAS G12D Mutations, Advanced Solid Tumors
- Being tested
- GFH375
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GFH375Drug
GFH375 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| GFH375 | Experimental | Not described Receives: Drug: GFH375 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase Ia:The incidence and severity of AEs and SAEs
The incidence and severity of AEs and SAEs
Measured: 24 months
Phase Ia:The incidence of DLT events
The incidence of DLT events
Measured: 21 days
Phase Ib:The incidence and severity of AEs and SAEs
The incidence and severity of AEs and SAEs
Measured: 24 months
Phase II:Overall response rate (ORR)
For NSCLC cohort： Assessed by BICR according to RECIST 1.1；For other cohorts： Assessed by investigators according to RECIST 1.1；
Measured: 24 months
Secondary outcomes (5)
Plasma concentrations
Plasma concentrations and PK parameters of GFH375
Measured: up to 21 days
Efficacy endpoints
Duration of response (DoR)
Measured: 24 months
Efficacy endpoints
Disease control rate (DCR)
Measured: 24 months
Efficacy endpoints
Progression free survival (PFS)
Measured: 24 months
Efficacy endpoints
Overall survival (OS)
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2024
- Study start9 Jul 2024
- Primary completion31 Jul 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for KRAS G12D MutationsStudies of the same condition, open and under way.
- More trials run by Genfleet Therapeutics (Shanghai) Inc.The sponsor's other registered studies.
- 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
- 407 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Genfleet Therapeutics (Shanghai) Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shun Lu, MD, Principal investigator, Shanghai Chest HospitalAiping Zhou, MD, Principal investigator, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06500676
- Sponsor's protocol ID
- GFH375X1101
- Status last verified
- Nov 2025
- First submitted
- 8 Jul 2024
- Last updated
- 20 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ai X, Song Z, Wu L, Zhou A, Cheng D, Zong H, Wu H, Niu Z, Sun Y, Zhu L, Li Z, Deng Y, Yuan Y, Qu X, Zhao H, Du Y, Li Z, Wang Y, Shen H, Zhu H, Zheng C, Wang S, Cui Z, Tai L, Lu S. Oral KRAS G12D inhibitor GFH375 for previously treated advanced solid tumors with KRASG12D mutations: a phase 1 trial. Nat Med. 2026 Sep;32(9):3302-3312. doi: 10.1038/s41591-026-04559-4. Epub 2026 Sep 15.
PubMed 42745055
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of GFH375 in Patients With KRAS G12D Mutant Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT06500676
- Acronym / sponsor ID
- GFH375X1101
- Conditions
- KRAS G12D Mutations, Advanced Solid Tumors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 407 participants (estimated)
- Lead sponsor
- Genfleet Therapeutics (Shanghai) Inc.Industry (pharma, biotech, devices)
- Study start
- 9 Jul 2024 (actual)
- Primary completion
- 31 Jul 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 15 Jul 2024 (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 a multicenter, open-label, phase I/II study to explore the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of GFH375 in patients with advanced solid tumors harboring a KRAS G12D mutation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GFH375 | Experimental | Drug: GFH375 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects must voluntarily agree to participate in the trial and sign a written informed consent form.
- Male or female ≥ 18 years old and ≤75 years old.
- ECOG performance status of 0-1.
- With a life expectancy of ≥12 weeks.
- With histologically or cytologically confirmed advanced or metastatic solid tumors harboring KRAS G12D mutation.
Key exclusion criteria (7 listed)
- Active brain metastases.
- Prior treatment with a KRAS G12D inhibitor.
- Palliative radiotherapy was completed within 14 days before the first dose.
- Have poorly controlled or severe cardiovascular disease.
- Subjects with active hepatitis B or active hepatitis C.
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 |
|---|---|---|
| GFH375GFH375 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity. | Drug | GFH375 |
Primary outcome
Phase Ia:The incidence and severity of AEs and SAEs
Time frame: 24 months
The incidence and severity of AEs and SAEs
Phase Ia:The incidence of DLT events
Time frame: 21 days
The incidence of DLT events
Phase Ib:The incidence and severity of AEs and SAEs
Time frame: 24 months
The incidence and severity of AEs and SAEs
Phase II:Overall response rate (ORR)
Time frame: 24 months
For NSCLC cohort： Assessed by BICR according to RECIST 1.1；For other cohorts： Assessed by investigators according to RECIST 1.1；
5 secondary outcomes
Plasma concentrations
Time frame: up to 21 days
Efficacy endpoints
Time frame: 24 months
Efficacy endpoints
Time frame: 24 months
Efficacy endpoints
Time frame: 24 months
Efficacy endpoints
Time frame: 24 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 20 Nov 2025.
- Derived from this study: PubMed 42745055Ai X, Song Z, Wu L, Zhou A, Cheng D, Zong H, Wu H, Niu Z, Sun Y, Zhu L, Li Z, Deng Y, Yuan Y, Qu X, Zhao H, Du Y, Li Z, Wang Y, Shen H, Zhu H, Zheng C, Wang S, Cui Z, Tai L, Lu S. Oral KRAS G12D inhibitor GFH375 for previously treated advanced solid tumors with KRASG12D mutations: a phase 1 trial. Nat Med. 2026 Sep;32(9):3302-3312. doi: 10.1038/s41591-026-04559-4. Epub 2026 Sep 15.
- Individual participant dataSharing planned: No
Related trials for KRAS G12D Mutations
RecruitingPhase 3
Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma ( RASolute 305 )
Pancreatic Cancer, Pancreatic Cancer Metastatic
RecruitingPhase 2
A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma (PDAC), G12D Mutated KRAS
RecruitingPhase 3
Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-Mutated Pancreatic Adenocarcinoma
Pancreatic Cancer, Pancreatic Cancer Metastatic
RecruitingPhase 3
Study of Pembrolizumab + Pemetrexed + Platinum Chemotherapy With or Without Zoldonrasib as First Line Treatment in Metastatic Non-squamous RAS G12D-Mutated NSCLC
NSCLC, Non-small Cell Lung Cancer
RecruitingPhase 3
A Study to Compare Setidegrasib (ASP3082) With Docetaxel, in People With Non-small Cell Lung Cancer With a KRAS G12D Mutation
Non-small Cell Lung Cancer (NSCLC)
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.
Shun Lu, MD principal investigator
Shanghai Chest Hospital
Aiping Zhou, MD principal investigator
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing GFH375 in people with KRAS G12D Mutations and Advanced Solid Tumors, run by Genfleet Therapeutics (Shanghai) Inc. at 20 sites 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 7 inclusion and 7 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 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites 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 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 Yolanda Zeng (+86 21 6882 1388, yaozeng@genfleet.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ia:The incidence and severity of AEs and SAEs (time frame: 24 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06500676, which also lists 1 linked publication.
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 20 Nov 2025.