T Cell Receptor Gene Therapy Targeting KK-LC-1 for Gastric, Breast, Cervical, Lung, and Other KK-LC-1 Positive Cancers
Christian Hinrichs
Summary
This is a phase I clinical trial to determine the maximum tolerated dose (MTD) of KK-LC-1 TCR-T cells for the treatment of metastatic cancers that express KK-LC-1. Participants will receive a conditioning regimen, KK-LC-1 TCR-T cells, and aldesleukin. The safety profile and clinical response to treatment will be determined.
Description
This study will determine the MTD of KK-LC-1 TCR-T cells for the treatment of metastatic cancers that express KK-LC-1 and will assess clinical tumor response to treatment. KK-LC-1 is an abnormal protein that is expressed by certain types of cancer. The cancers that most commonly express KK-LC-1 include gastric, lung, breast, and cervix cancer. KK-LC-1 TCR-T cells are autologous T cells that are genetically engineered to target the KK-LC-1 antigen. Tumor targeting by the KK-LC-1 TCR requires that subjects have the the HLA-A\*01:01 allele. Participants will receive a conditioning regimen consist…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
1\. Inclusion Criteria: Subjects must meet all the following criteria to participate in this study. 1. Signed, written informed consent obtained prior to any study procedures. 2. Age \> 18 years at the time of informed consent. 3. Metastatic solid tumor with ≥ 10% of tumor cells positive for KK-LC-1 by IHC assay. Due to the low frequency of KK-LC-1 expression in most cancers, screening will focus on gastric, NSCLC, TNBC, and cervix cancers. The IHC test will be performed by the Rutgers Cancer Institute, Department of Biorepository Services. 4. HLA-A\*01:01 allele by HLA haplotype test. 5. Mea…
Interventions
- BiologicalKK-LC-1 TCR-T cells
Participants will receive a conditioning regimen consisting of cyclophosphamide and fludarabine. KK-LC-1 TCR-T cells will be administered as a single intravenous infusion.
- DrugAldesleukin
Aldesleukin 720,000 IU/kg IV every 8 hours will be preferentially administered as an inpatient within 24 hours after KK-LC-1 TCR-T cell infusion for up to 6 doses; however up to 24 hours may elapse between doses. Aldesleukin dosing will be stopped for aldesleukin-related grade 3 or greater toxicity other than flushing, fever, chills, or hemodynamic changes (tachycardia or hypotension) that respond to crystalloid infusion. Aldesleukin may also be stopped at any time at investigator discretion.
Locations (2)
- Rutgers Cancer Institute of New JerseyNew Brunswick, New Jersey
- RWJBarnabas Health - Robert Wood Johnson University HospitalNew Brunswick, New Jersey