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.
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: 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
Single group
Bendamustine
DrugReceive IV
Biopsy
Procedure/SurgeryUndergo tissue biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT
Cyclophosphamide
DrugReceive IV
Echocardiography
Procedure/SurgeryUndergo ECHO
Fludarabine
DrugReceive IV
Leukapheresis
Procedure/SurgeryUndergo leukapheresis
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Positron Emission Tomography
Procedure/SurgeryUndergo PET
T-cell Receptor-engineered T-cells
Biological/VaccineReceive FHA11KRASG12V-TCR IV
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).
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%.
Maximum tolerated dose of FH-A11KRASG12V-TCR
Will be assessed by NCI CTCAE v5.0.
Recommended phase 2 dose of FH-A11KRASG12V-TCR
Will be assessed by NCI CTCAE v5.0.
Reproducibly generating FHA11KRASG12V- TCR from autologous participant cells (Feasibility)
Defined as the ability to reproducibly generate and infuse the T cells for eligible participants and a simple estimate of the proportion along with its 95% confidence interval will be used. Standard methods will be used to estimate each of the secondary endpoints.
Overall response rate (ORR)
Will be assessed by complete (CR) and partial responses (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in treated individuals. Standard methods will be used to estimate each of the secondary endpoints.
Stable disease (SD)
Will be assessed by RECIST 1.1 criteria in treated individuals. Standard methods will be used to estimate each of the secondary endpoints.
Clinical benefit rate (CBR)
CBR will be defined as ORR + SD. Will be assessed by RECIST 1.1 criteria in treated individuals. Standard methods will be used to estimate each of the secondary endpoints.
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Fred Hutchinson Cancer Center
Lead sponsor
Affini-T Therapeutics, Inc.
Collaborator
National Cancer Institute (NCI)
Collaborator
