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

NCT06043713 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: RG1123135NCI-2023-06287200482P50CA228944
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of autologous CD8+ and CD4+ transgenic T cells expressing high affinity KRASG12V mutation-specific T cell receptors (FH-A11KRASG12V-TCR) and to see how well they work in treating patients with solid tumor cancers that has spread from where it first started (primary site) to other places in the body (metastatic). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize KRAS G12V, a protein on the surface of tumor cells. These KRAS G12V-specific T cells may help the body's immune system identify and kill KRAS G12V solid cancer tumor cells.

Conditions

Metastatic Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (4)

• Incidence of adverse events

  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).

  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)

• Dose-limiting toxicity rates

  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%.

  From the time of lymphodepletion chemotherapy to 28 days after FH-A11KRASG12V-TCR infusion

• Maximum tolerated dose of FH-A11KRASG12V-TCR

  Will be assessed by NCI CTCAE v5.0.

  From the time of lymphodepletion chemotherapy to 28 days after FH-A11KRASG12V-TCR infusion

• Recommended phase 2 dose of FH-A11KRASG12V-TCR

  Will be assessed by NCI CTCAE v5.0.

  Within 1 year after 1st infusion of FH-A11KRASG12V-TCR

Secondary Outcomes (8)

• Reproducibly generating FHA11KRASG12V- TCR from autologous participant cells (Feasibility)

  Within 1 year after eligibility determination

• Overall response rate (ORR)

  Within 1 year after 1st infusion of FH-A11KRASG12V-TCR

• Stable disease (SD)

  Within 1 year after 1st infusion of FH-A11KRASG12V-TCR

• Clinical benefit rate (CBR)

  Within 1 year after 1st infusion of FH-A11KRASG12V-TCR

• ORR

  Within 1 year after 1st infusion of FH-A11KRASG12V-TCR

Study Arms (1)

Treatment (FHA11KRASG12V-TCR)

EXPERIMENTAL

Patients undergo leukapheresis prior to treatment and receive lymphodepletion chemotherapy with either cyclophosphamide IV and fludarabine IV on days -6, -5, and -4, or bendamustine IV on days -4 and -3 at the discretion of the treating clinician and/or PI. Patients then receive FHA11KRASG12V-TCR IV on day 0. Patients may receive an additional FHA11KRASG12V-TCR IV infusion as soon as 28 days or up to 1 year after the first infusion. Patients undergo ECHO or MUGA during screening. Patients also undergo CT, PET or MRI as well as blood sample collection and a tissue biopsy at baseline and throughout the trial.

Drug: Bendamustine; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Cyclophosphamide; Procedure: Echocardiography; Drug: Fludarabine; Procedure: Leukapheresis; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography; Biological: T-cell Receptor-engineered T-cells

Interventions

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (FHA11KRASG12V-TCR)

Cyclophosphamide DRUG

Receive IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (FHA11KRASG12V-TCR)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (FHA11KRASG12V-TCR)

Fludarabine DRUG

Receive IV

Also known as: Fluradosa

Treatment (FHA11KRASG12V-TCR)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Treatment (FHA11KRASG12V-TCR)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (FHA11KRASG12V-TCR)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning, RNV Scan

Treatment (FHA11KRASG12V-TCR)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (FHA11KRASG12V-TCR)

T-cell Receptor-engineered T-cells BIOLOGICAL

Receive FHA11KRASG12V-TCR IV

Also known as: T-cell Receptor-engineered T Cells, T-cell Receptor-engineered T-lymphocytes, TCR T Cells, TCR T-cells, TCR-engineered T-cells, TCR-modified T Cells, FH-A11KRASG12V-TCR, AFNT-111

Treatment (FHA11KRASG12V-TCR)

Bendamustine DRUG

Receive IV

Also known as: SDX-105

Treatment (FHA11KRASG12V-TCR)

Biopsy PROCEDURE

Undergo tissue biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (FHA11KRASG12V-TCR)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (FHA11KRASG12V-TCR)

Eligibility Criteria

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

You may qualify if:

• 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, subjects 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 subjects 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Affini-T Therapeutics, Inc.: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Bendamustine Hydrochloride; Biopsy; Specimen Handling; Cyclophosphamide; fludarabine; Leukapheresis; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Elena Chiorean

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fred Hutch Intake

CONTACT

206-606-1024; hutchdoc@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: September 21, 2023
• Study Start: December 15, 2023
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)