Pancreatic CancerPhase 1/2NCT04146298
Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer
A Phase 1/2 study testing Cyclophosphamide, Fludarabine and Mutant KRAS G12V-specific TCR transduced autologous T cells in people with Pancreatic Cancer and Pancreatic Neoplasms, run by Changhai Hospital at 1 site in China.
Trial summary
This clinical trial will evaluate the safety and activity of mutant KRAS G12V-specific TCR transduced T cell therapy for advanced pancreatic cancer patients who express the KRAS G12V mutation and HLA-A*11:01 allele. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pancreatic Cancer, Pancreatic Neoplasms, Pancreatic Ductal Adenocarcinoma
- What is being tested?
- Cyclophosphamide, Fludarabine and Mutant KRAS G12V-specific TCR transduced autologous T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 21 Oct 2021to 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
- Patients with measurable and pathologically confirmed advanced pancreatic cancer, including metastatic pancreatic cancer (who have received standard chemotherapy) and recurrent pancreatic cancer (who have received surgery and adjuvant chemotherapy previously).
- Patient's tumor must express the KRAS G12V mutation, or a G12V mutation in HRAS or NRAS, as determined by DNA or RNA sequencing methods.
- Patients must be HLA-A*11:01.
- Patients with brain metastasis may be eligible if they are asymptomatic and there are fewer than 3 brain lesions that are each less than 1 cm in diameter.
- Patients between 18 to 75 years old are eligible.
- Patients should have good clinical performance status (ECOG 0 or 1).
Show all 22Show fewer
- Patients must practice birth control once enrolled into the study and for up to four months after therapy.
- Patients must be seronegative for HIV antibody.
- Patients must be seronegative for hepatitis B surface antigen and core antibody (or HBV non-detectable by QPCR).
- Patients must be seronegative for hepatitis C antibody (or HCV non-detectable by QPCR).
- Baseline hematology criteria:
- Absolute neutrophil count of at least 1000/mm^3.
- White blood cell count of at least 3000/mm^3.
- Platelet count of at least 100,000/mm^3.
- Hemoglobin > 8.0 g/dL.
- Baseline chemistry criteria:
- Serum ALT/AST less than or equal to 3.0 x ULN.
- Total bilirubin less than or equal to 1.5 mg/dL, unless the patient has Gilbert's Syndrome in which case total bilirubin must be less than or equal to 3.0 mg/dL.
- Serum creatinine less than or equal to 1.6 mg/dL.
- Anticipated lifespan greater than 12 weeks.
- Patients must be willing and able to comply with all study-related procedures and follow-up requirements.
- Patients must be able to understand and sign a written Informed Consent Document as well as a durable power of attorney.
Who cannot join
- Women who are pregnant or breastfeeding.
- Patients with any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease or HIV).
- Patients with active systemic infections, coagulation disorders, or any other major medical illnesses.
- Patients with concurrent opportunistic infections.
- Patients on concurrent systemic steroid therapy.
- Patients with a history of severe immediate hypersensitivity reaction to any of the medicines used in this study (e.g., cyclophosphamide, fludarabine).
- Patients with active coronary ischemic symptoms.
- Patients who are receiving any other investigational agents.
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
- Recruiting
Changhai Hospital
Shanghai, 200433
Shiwei Guo, Doctor, +8618621500666, gestwa@163.com
Gang Jin, Doctor
About this study
Official title: Clinical Trial Evaluating the Safety and Activity of Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer
This clinical trial will evaluate the safety and activity of mutant KRAS G12V-specific TCR transduced T cell therapy for advanced pancreatic cancer patients who express the KRAS G12V mutation and HLA-A*11:01 allele. The theoretical basis of this study is that mutant KRAS antigen-specific TCR transduced autologous Tcells will target and kill HLA-matched mutant KRAS cancer cells but not normal cells.
Read the detailed description
Hotspot KRAS mutations exist in various cancers, especially pancreatic, lung and colorectal cancer. Mutations in KRAS are implicated in the development of pancreatic cancer and are associated with poor prognosis of the patients. KRAS is an attractive target for cancer treatment because it is a driver mutation and is likely expressed by all cells in a tumor. Recently,T cells targeting mutant KRAS have been identified in patients with epithelial cancers, and these T-cell receptors (TCR) have been characterized. For example, TCRs that target mutant KRAS G12D peptides presented by HLA-C*08:02, and a TCR that targets a KRAS G12V peptide presented by HLA-A*11:01 have been identified. Mutant KRAS-reactive T cells appear capable of inducing tumor regression as highlighted in a patient with metastatic colorectal cancer who experienced regression of metastatic tumors after infusion of HLA-C*08:02-restricted KRAS-G12D reactive tumor-infiltrating lymphocytes (TIL). The investigators will test the safety and activity of adoptive transfer of autologous T cells genetically engineered to express a TCR that targets mutant KRAS G12V in the context of HLA-A*11:01 in HLA-matched patients with advanced pancreatic cancer that express mutant KRAS G12V. The investigators will also measure the in vivo survival of engineered T cells.
- Conditions
- Pancreatic Cancer, Pancreatic Neoplasms, Pancreatic Ductal Adenocarcinoma, Advanced Cancer
- Being tested
- Cyclophosphamide, Fludarabine, Mutant KRAS G12V-specific TCR transduced autologous T cells, Anti-PD-1 monoclonal antibody
- Keywords
- pancreatic cancer, TCR transduced T cells, adoptive cell therapy, KRAS
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Cyclophosphamide will be administered prior to cell infusion.
FludarabineDrug
Fludarabine will be administered prior to cell infusion.
Mutant KRAS G12V-specific TCR transduced autologous T cellsBiological
After preconditioning regimen, T cells will be infused to the patient intravenously in the Patient Care Unit over approximately 30 to 50 minutes.
Anti-PD-1 monoclonal antibodyDrug
Also called Anti-PD-1
During the treatment, anti-PD-1 monoclonal antibody will be administered if needed.
| Study group | Role | What they receive |
|---|---|---|
| TCR Transduced T cell therapy | Experimental | Pre-conditioning: Non-myeloablative, lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine
TCR transduced T cell infusion: mutant KRAS G12V-specific TCR transduced autologous T cells (1e9~1e11). If the participant responds to the first infusion, the second or more infusions will be considered when the disease is progressing.
Anti-PD-1 therapy: anti-PD-1 will be administered if needed. Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Mutant KRAS G12V-specific TCR transduced autologous T cells; Drug: Anti-PD-1 monoclonal antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency and severity of treatment-related adverse events
Aggregate of all adverse events, as well as their frequency and severity
Measured: 18 months following cell infusion
Objective response rate
Percentage of patients who have a clinical response to treatment (objective tumor regression)
Measured: From the date of cell infusion to disease progression (up to 18 months after cell infusion).
Secondary outcomes (2)
The percentage of TCR transduced T cells in peripheral blood
The percentage of TCR transduced T cells in peripheral blood will be detected with an established flow cytometric assay.
Measured: 1, 3, 7, 14, 28, 42 and 84 days after cell infusion, then every 3 months, and up to 18 months after cell infusion.
Overall survival
The time between cell infusion and the death of patients
Measured: From date of cell infusion until the date of death from any cause, whichever came first, assessed up to 18 months after cell infusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2019
- Study start21 Oct 2021
- Primary completionJun 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by Changhai HospitalThe 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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Changhai Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Guo ShiWei, Changhai Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04146298
- Sponsor's protocol ID
- ChanghaiH-PP06
- Status last verified
- Aug 2025
- First submitted
- 26 Oct 2019
- Last updated
- 24 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Xu X, Guo S, Gu H, Cha Z, Shi X, Yin X, Wang H, Gao S, Li B, Zhu L, Jing W, Zheng K, Shao Z, Cheng P, Zheng C, Shih YP, Li Y, Qian B, Gao D, Tran E, Jin G. Identification and validation of a T cell receptor targeting KRAS G12V in HLA-A*11:01 pancreatic cancer patients. JCI Insight. 2025 Jan 23;10(2):e181873. doi: 10.1172/jci.insight.181873.
PubMed 39846249Cafri G, Yossef R, Pasetto A, Deniger DC, Lu YC, Parkhurst M, Gartner JJ, Jia L, Ray S, Ngo LT, Jafferji M, Sachs A, Prickett T, Robbins PF, Rosenberg SA. Memory T cells targeting oncogenic mutations detected in peripheral blood of epithelial cancer patients. Nat Commun. 2019 Jan 25;10(1):449. doi: 10.1038/s41467-019-08304-z.
PubMed 30683863Tran E, Robbins PF, Lu YC, Prickett TD, Gartner JJ, Jia L, Pasetto A, Zheng Z, Ray S, Groh EM, Kriley IR, Rosenberg SA. T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer. N Engl J Med. 2016 Dec 8;375(23):2255-2262. doi: 10.1056/NEJMoa1609279.
PubMed 27959684
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial Evaluating the Safety and Activity of Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT04146298
- Acronym / sponsor ID
- ChanghaiH-PP06
- Conditions
- Pancreatic Cancer, Pancreatic Neoplasms, Pancreatic Ductal Adenocarcinoma, Advanced Cancer
- Keywords
- pancreatic cancer, TCR transduced T cells, adoptive cell therapy, KRAS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Changhai HospitalUniversity, hospital or other
- Study start
- 21 Oct 2021 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 31 Oct 2019 (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 clinical trial will evaluate the safety and activity of mutant KRAS G12V-specific TCR transduced T cell therapy for advanced pancreatic cancer patients who express the KRAS G12V mutation and HLA-A*11:01 allele. The theoretical basis of this study is that mutant KRAS antigen-specific TCR transduced autologous Tcells will target and kill HLA-matched mutant KRAS cancer cells but not normal cells.
Detailed description
Hotspot KRAS mutations exist in various cancers, especially pancreatic, lung and colorectal cancer. Mutations in KRAS are implicated in the development of pancreatic cancer and are associated with poor prognosis of the patients. KRAS is an attractive target for cancer treatment because it is a driver mutation and is likely expressed by all cells in a tumor. Recently,T cells targeting mutant KRAS have been identified in patients with epithelial cancers, and these T-cell receptors (TCR) have been characterized. For example, TCRs that target mutant KRAS G12D peptides presented by HLA-C*08:02, and a TCR that targets a KRAS G12V peptide presented by HLA-A*11:01 have been identified. Mutant KRAS-reactive T cells appear capable of inducing tumor regression as highlighted in a patient with metastatic colorectal cancer who experienced regression of metastatic tumors after infusion of HLA-C*08:02-restricted KRAS-G12D reactive tumor-infiltrating lymphocytes (TIL). The investigators will test the safety and activity of adoptive transfer of autologous T cells genetically engineered to express a TCR that targets mutant KRAS G12V in the context of HLA-A*11:01 in HLA-matched patients with advanced pancreatic cancer that express mutant KRAS G12V. The investigators will also measure the in vivo survival of engineered T cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TCR Transduced T cell therapy | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Biological: Mutant KRAS G12V-specific TCR transduced autologous T cells, Drug: Anti-PD-1 monoclonal antibodyPre-conditioning: Non-myeloablative, lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine TCR transduced T cell infusion: mutant KRAS G12V-specific TCR transduced autologous T cells (1e9~1e11). If the participant responds to the first infusion, the second or more infusions will be considered when the disease is progressing. Anti-PD-1 therapy: anti-PD-1 will be administered if needed. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Patients with measurable and pathologically confirmed advanced pancreatic cancer, including metastatic pancreatic cancer (who have received standard chemotherapy) and recurrent pancreatic cancer (who have received surgery and adjuvant chemotherapy previously).
- Patient's tumor must express the KRAS G12V mutation, or a G12V mutation in HRAS or NRAS, as determined by DNA or RNA sequencing methods.
- Patients must be HLA-A*11:01.
- Patients with brain metastasis may be eligible if they are asymptomatic and there are fewer than 3 brain lesions that are each less than 1 cm in diameter.
- Patients between 18 to 75 years old are eligible.
Key exclusion criteria (8 listed)
- Women who are pregnant or breastfeeding.
- Patients with any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease or HIV).
- Patients with active systemic infections, coagulation disorders, or any other major medical illnesses.
- Patients with concurrent opportunistic infections.
- Patients on concurrent systemic steroid therapy.
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 |
|---|---|---|
| CyclophosphamideCyclophosphamide will be administered prior to cell infusion. | Drug | TCR Transduced T cell therapy |
| FludarabineFludarabine will be administered prior to cell infusion. | Drug | TCR Transduced T cell therapy |
| Mutant KRAS G12V-specific TCR transduced autologous T cellsAfter preconditioning regimen, T cells will be infused to the patient intravenously in the Patient Care Unit over approximately 30 to 50 minutes. | Biological | TCR Transduced T cell therapy |
| Anti-PD-1 monoclonal antibodyAlso: Anti-PD-1During the treatment, anti-PD-1 monoclonal antibody will be administered if needed. | Drug | TCR Transduced T cell therapy |
Primary outcome
Frequency and severity of treatment-related adverse events
Time frame: 18 months following cell infusion
Aggregate of all adverse events, as well as their frequency and severity
Objective response rate
Time frame: From the date of cell infusion to disease progression (up to 18 months after cell infusion).
Percentage of patients who have a clinical response to treatment (objective tumor regression)
2 secondary outcomes
The percentage of TCR transduced T cells in peripheral blood
Time frame: 1, 3, 7, 14, 28, 42 and 84 days after cell infusion, then every 3 months, and up to 18 months after cell infusion.
Overall survival
Time frame: From date of cell infusion until the date of death from any cause, whichever came first, assessed up to 18 months after cell infusion.
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 24 Dec 2025.
- Results publication: PubMed 39846249Xu X, Guo S, Gu H, Cha Z, Shi X, Yin X, Wang H, Gao S, Li B, Zhu L, Jing W, Zheng K, Shao Z, Cheng P, Zheng C, Shih YP, Li Y, Qian B, Gao D, Tran E, Jin G. Identification and validation of a T cell receptor targeting KRAS G12V in HLA-A*11:01 pancreatic cancer patients. JCI Insight. 2025 Jan 23;10(2):e181873. doi: 10.1172/jci.insight.181873.
- Results publication: PubMed 30683863Cafri G, Yossef R, Pasetto A, Deniger DC, Lu YC, Parkhurst M, Gartner JJ, Jia L, Ray S, Ngo LT, Jafferji M, Sachs A, Prickett T, Robbins PF, Rosenberg SA. Memory T cells targeting oncogenic mutations detected in peripheral blood of epithelial cancer patients. Nat Commun. 2019 Jan 25;10(1):449. doi: 10.1038/s41467-019-08304-z.
- Results publication: PubMed 27959684Tran E, Robbins PF, Lu YC, Prickett TD, Gartner JJ, Jia L, Pasetto A, Zheng Z, Ray S, Groh EM, Kriley IR, Rosenberg SA. T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer. N Engl J Med. 2016 Dec 8;375(23):2255-2262. doi: 10.1056/NEJMoa1609279.
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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.
1 site 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 Cyclophosphamide, Fludarabine and Mutant KRAS G12V-specific TCR transduced autologous T cells in people with Pancreatic Cancer and Pancreatic Neoplasms, run by Changhai Hospital 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 22 inclusion and 8 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 24 Dec 2025. 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 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 Shiwei Guo, Doctor (+8618621500666, gestwa@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency and severity of treatment-related adverse events (time frame: 18 months following cell infusion). The study lists 2 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 NCT04146298, which also lists 3 linked publications.
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 24 Dec 2025.