FH-A11KRASG12V-TCR for Metastatic Solid Tumors with KRAS G12V Mutations
This study is testing a treatment called FH-A11KRASG12V-TCR for people with metastatic solid tumors that have a specific genetic change called KRAS G12V. Metastatic means the cancer has spread from where it started. FH-A11KRASG12V-TCR uses your own infection-fighting blood cells (T cells) that are specially trained to find and kill cancer cells with the KRAS G12V change. Before receiving these T cells, you will get chemotherapy (Bendamustine or Cyclophosphamide). The main goals are to find the safest dose of FH-A11KRASG12V-TCR and to see how well it works. To join, you must have a metastatic solid tumor with the KRAS G12V mutation and meet other specific criteria, including a certain immune system marker (HLA-A*11:01). The current status of this study is unclear.
- Study design
- This is a dose-escalation study, meaning participants will receive increasing doses of FH-A11KRASG12V-TCR to find the safest and most effective amount. It plans to enroll 24 participants.
- What's involved
- You would undergo leukapheresis (a procedure to collect blood cells), receive chemotherapy, and then get infusions of FH-A11KRASG12V-TCR. You will also have blood draws, CT scans, and tissue biopsies at various times.
- Compensation
- Not stated in the trial record.
- Follow-up
- After treatment, you will be followed for up to 15 years to monitor your health and the treatment's long-term effects.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT06043713
Autologous CD8+ and CD4+ Transgenic T Cells Expressing High Affinity KRASG12V Mutation-Specific T Cell Receptors (FH-A11KRASG12V-TCR) in Treating Patients With Metastatic Solid Tumor Cancers With KRAS G12V Mutations
Recruiting
PHASE1Ages 18+InterventionalTreatmentFred Hutchinson Cancer CenterInvestigator-initiated
~24 participants
Updated 2026-07-06 on ClinicalTrials.gov
What's tested:BendamustineBiopsyBiospecimen CollectionComputed TomographyCyclophosphamideEchocardiography
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Incidence of adverse events
Measured over Within 1 year after 1st infusion of (autologous CD8+ and CD4+ transgenic T cells expressing high affinity KRASG12V mutation-specific T cell receptors (FH-A11KRASG12V-TCR)
+3 more outcomes measured
Conditions
NCT06043713
Where you'd take part
This study runs at 1 site. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washingtonstudy coordinator listed
Recruiting
Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.
Study leadership
- Rachael Safyan, MD · PRINCIPAL_INVESTIGATOR · Fred Hutch/University of Washington Cancer Consortium
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Want this trial checked against your situation?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
LEUKAPHERESIS: Diagnosis of metastatic solid tumor
LEUKAPHERESIS: Tissue confirmation of solid tumor. Confirmation of diagnosis must be or have been performed by internal pathology review of archival biopsy material or other pathologic material at Fred Hutch/University of Washington Cancer Consortium (UWMC)
LEUKAPHERESIS: HLA-A\*11:01 confirmed through HLA typing at a clinically accredited laboratory
LEUKAPHERESIS: Previously documented KRASG12V mutation in tumor or plasma cell-free deoxyribonucleic acid (cfDNA) specimens by polymerase chain reaction (PCR) or next-generation sequencing (NGS) test
LEUKAPHERESIS: Measurable disease by RECIST 1.1 criteria: Participants must have measurable disease, defined as at least one target lesion that can be measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm, unless lymph node in which case short axis must be ≥ 15 mm. Baseline imaging (for example, diagnostic CT chest/abdomen/pelvis and imaging of the affected extremity as appropriate), brain imaging (MRI or CT scan) if clinically indicated, must be obtained within 8 weeks of the first planned T cell infusion. MRI can be substituted for CT in participants unable to have CT contrast
LEUKAPHERESIS: Participants must be willing to undergo tumor biopsy for research purposes if safe and feasible at baseline (prior to first T cell infusion), 2-3 weeks after the first T cell infusion, and approximately 2 weeks +/- 1 week after the 2nd infusion (if applicable), if safe and feasible (these time windows may vary due to manufacturing or clinical reasons). Should there be no tumor tissue that is accessible for biopsy, participants will still be considered for participation, at the discretion of the investigator. Similarly, should an investigator determine that a biopsy cannot be performed safely for clinical reasons, biopsies may be cancelled or rescheduled. Patients can also refuse biopsies at any time after enrollment
LEUKAPHERESIS: Participants must be at least two weeks or five half-lives (for small molecules) from last systemic treatment: At least 2 weeks must have passed since any: immunotherapy (for example, T-cell infusions, immunomodulatory agents, interleukins, vaccines), or chemotherapy cancer treatment. At least five half-lives must have passed from treatment with small molecules or other investigational agents. There is no washout period for radiation, so long as radiated lesion is not the lesion being evaluated for RECIST measurements on the protocol. Bisphosphonates and denosumab are permitted
LEUKAPHERESIS: Participants must have progressed on or be intolerant to at least one lines of prior therapy including any targeted therapies indicated for participants with each of the tumor types eligible to enroll, as applicable
LEUKAPHERESIS: Patients with solid tumors harboring targetable molecular alterations including but not limited to EGFR mutations, ALK, ROS, NTRK fusions, microsatellite instability (MSI)-high, tumor mutational burden (TMB) high, BRAF v600 mutations, HER2 amplifications, must have been treated or refused treatment with applicable targeted therapies, as applicable
LEUKAPHERESIS: Fertile male and female participants must be willing to use an effective contraceptive method before, during, and for at least 4 months after the last A11KRASG12V-TCR infusion
LEUKAPHERESIS: 18 years or older at the time of enrollment
LEUKAPHERESIS: Capable of understanding and providing a written informed consent
LEUKAPHERESIS: Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1
No uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days
LEUKAPHERESIS: No uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days
LEUKAPHERESIS: Renal: Creatinine clearance \>= 50 ml/min by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or 24-hour urine clearance
LEUKAPHERESIS: Hepatic: Total bilirubin \< 2.0 mg/dL
LEUKAPHERESIS: Hepatic: Aspartate transferase (AST) and alanine transaminase (ALT) \< 5x upper limit of normal (ULN)
LEUKAPHERESIS: Hepatic: Participants with suspected Gilbert syndrome may be included if total bilirubin (Bili) \> 3 mg/dL but no other evidence of hepatic dysfunction
LEUKAPHERESIS: Cardiac: Participants 60 years of age or older are required to have left ventricular ejection fraction (LVEF) evaluation performed within 60 days prior to enrollment. LVEF may be established with echocardiogram or MUGA scan, and LVEF must be \>= 35%. Cardiac evaluation for other participants is at the discretion of the treating physician
LEUKAPHERESIS: Hematologic: Absolute neutrophil count (ANC) \>= 1000 cells/ mm\^3
LEUKAPHERESIS: Nutrition: Albumin \>= 3 g/dL
START OF TREATMENT: Measurable disease by RECIST 1.1 criteria: Participants must have measurable disease, defined as at least one target lesion that can be measured in at least one dimension (longest diameter to be recorded) as \>= 10 mm, unless lymph node in which case short axis must be \>= 15 mm. Baseline imaging (for example, diagnostic CT chest/abdomen/pelvis and imaging of the affected extremity as appropriate), brain imaging (MRI or CT scan) must be obtained within 8 weeks of the first planned T cell infusion. MRI can be substituted for CT in participants unable to have CT contrast
START OF TREATMENT: Participants must be willing to undergo tumor biopsy for research purposes if safe and feasible at baseline (prior to first T cell infusion), 2-3 weeks after the first T cell infusion, and approximately 2 weeks +/- 1 week after the 2nd infusion (if applicable), if safe and feasible (these windows may vary due to manufacturing or clinical reasons). Should there be no tumor tissue that is accessible for biopsy, participants will still be considered for participation, at discretion of the investigator. Similarly, should an investigator determine that a biopsy cannot be performed safely for clinical reasons, biopsies may be cancelled or rescheduled
START OF TREATMENT: Participants must be at least two weeks from last systemic treatment: At least 2 weeks must have passed since any: immunotherapy (for example, T-cell infusions, immunomodulatory agents, interleukins, vaccines), or chemotherapy cancer treatment. At least five half-lives must have passed from treatment with small molecules or other investigational agents. There is no washout period for radiation, so long as radiated lesion is not the lesion being evaluated for RECIST measurements on the protocol. Bisphosphonates and denosumab are permitted
START OF TREATMENT: ECOG performance status of =\< 1
START OF TREATMENT: Renal: Creatinine clearance \>= 50 ml/min by CKD-EPI or 24-hour urine clearance
Exceptions may be at the discretion of the PI to allow participants with organ function affected by their organ-specific tumor involvement
START OF TREATMENT: Hepatic: Total bilirubin \< 2.0 mg/dL
Exceptions may be at the discretion of the PI to allow participants with organ function affected by their organ-specific tumor involvement
START OF TREATMENT: AST and ALT \< 5x upper limit of normal (ULN)
START OF TREATMENT: Participants with suspected Gilbert syndrome may be included if total Bili \> 3 mg/dl but no other evidence of hepatic dysfunction
START OF TREATMENT: Pulmonary: =\< grade 1 dyspnea and oxygen saturation of arterial blood (SaO2) \>= 92% on ambient air. If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, participants with forced expiratory volume in the first second (FEVI) \>= 50% of predicted and diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected) \>= 40% of predicted will be eligible
Exceptions may be at the discretion of the PI to allow participants with organ function affected by their organ-specific tumor involvement
START OF TREATMENT: Hematologic: ANC \>= 1000 cells/ mm\^3
Exceptions may be at the discretion of the PI to allow participants with organ function affected by their organ-specific tumor involvement
START OF TREATMENT: Nutrition: Albumin \>= 3 g/dL
Exceptions may be at the discretion of the PI to allow participants with organ function affected by their organ-specific tumor involvement
START OF TREATMENT: Participants with a history of chronic obstructive pulmonary disease (COPD), emphysema, or greater than 30 pack year smoking history should undergo PFTs and meet the following criteria:
FEVI \>= 50% of predicted and DLCO (corrected) \>= 40% of predicted will be eligible
START OF TREATMENT: Active treatment for prior immune related adverse event to any immunotherapy: Participants receiving ongoing treatment for prior serious immune-related adverse events are excluded, with exception of hormone supplementation or corticosteroid therapy at equivalent of up to 0.5mg/kg/day prednisone per day, unless otherwise approved by PI
START OF TREATMENT: Other medical, social, or psychiatric factor that interferes with medical appropriateness and/or ability to comply with study, as determined by the PI
START OF TREATMENT: Known allergic reactions to any of the components of study treatments
START OF TREATMENT: Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days
Exclusion
LEUKAPHERESIS: Prior solid organ transplant or allogeneic hematopoietic stem cell transplant: Kidney transplant participants will be considered on a case-by-case basis requiring discussion with PI. If the participant has had a kidney transplant, participant must have dialysis access, dialysis plan, supportive nephrologist, willingness to stop transplant immunosuppression, and express understanding that rejection is possible outcome. Dialysis or costs related to transplant kidney will not be supported by the study. Participants having had any other solid organ transplants will be excluded, as will those with any history of allogeneic hematopoietic stem cell transplant
START OF TREATMENT: Pregnancy, breastfeeding, or expecting to conceive or father children for the duration of the trial through 4 months after last T-cell infusion. Participants of childbearing potential must have a negative serum pregnancy test within the 2 weeks (14 days) preceding T cell infusion. Childbearing potential is defined as women who have not been surgically sterilized and who are not post-menopausal (free of menses for at least 1 year)
START OF TREATMENT: Active autoimmune disease: Participants with active autoimmune disease requiring immunosuppressive therapy are excluded. Case by case exemptions are possible with approval by PI
START OF TREATMENT: Corticosteroid therapy at a dose equivalent of \> 0.5 mg/kg of prednisone per day. The following treatments are permitted: intranasal, inhaled, topical, or local steroid applications; systemic corticosteroids at physiologic doses equivalent to no more than \> 0.5 mg/kg/day prednisone; steroids as premedication for contrast dye allergy
START OF TREATMENT: Concurrent use of other investigational anti-cancer agents
START OF TREATMENT: Active uncontrolled infection: Human immunodeficiency virus (HIV) positive participants on highly active antiretroviral therapy (HAART) with a CD4 count \> 500 cells/mm\^3 are considered controlled, as are individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have hepatitis well controlled on medication
START OF TREATMENT: Uncontrolled concurrent illness: Participants may not have uncontrolled or concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
What this trial measures
- Incidence of adverse eventsWithin 1 year after 1st infusion of (autologous CD8+ and CD4+ transgenic T cells expressing high affinity KRASG12V mutation-specific T cell receptors (FH-A11KRASG12V-TCR)
Safety and tolerability should be evaluated after each infusion. Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0).
- Dose-limiting toxicity ratesFrom the time of lymphodepletion chemotherapy to 28 days after FH-A11KRASG12V-TCR infusion
Will be assessed by treatment-related grade 3 or higher toxicity and assessed by NCI CTCAE v5.0. The treatment will be considered to have an acceptable safety profile if the observed toxicity rate is consistent with a true rate that does not exceed 35%.
- Maximum tolerated dose of FH-A11KRASG12V-TCRFrom the time of lymphodepletion chemotherapy to 28 days after FH-A11KRASG12V-TCR infusion
Will be assessed by NCI CTCAE v5.0.
- Recommended phase 2 dose of FH-A11KRASG12V-TCRWithin 1 year after 1st infusion of FH-A11KRASG12V-TCR
Will be assessed by NCI CTCAE v5.0.