T Cell Receptor Gene Therapy Targeting KK-LC-1 for Gastric, Breast, Cervical, Lung and Other KK-LC-1 Positive Epithelial Cancers

Study Summary

Background: Researchers have found a new way to treat cancer using T cell therapy. The therapy used in this study is T Cell Receptor (TCR) Gene Therapy Targeting Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1), a cancer germline antigen that is expressed by certain cancers. This therapy is a type of treatment in which participants T cells (a type of immune system white blood cell) are changed in the laboratory to attack cancer cells and given back to the participant. This treatment might help people with KK-LC-1 positive cancers which may include gastric, breast, cervical, lung and other epithelial Cancers. Epithelial cancers are cancers that begin in the cells that line an organ. Objective: The purpose of this study is to determine the safety of different doses of KK-LC-1 TCR T cells plus aldesleukin to treat metastatic or refractory/recurrent KK-LC-1 positive cancers. Eligibility: Adults aged 18 and older with metastatic or refractory/recurrent KK-LC-1 positive epithelial cancer. Design: Participants will be screened with human leukocyte antigen (HL)typing (a blood test needed for eligibility) and KK-LC-1 testing of the cancer tumor (to determine if the cancer is KK-LC-1 positive). A new biopsy may be needed if tumor from an outside location is not available for KK-LC-1 testing. Eligible participants will come to the National Institutes of Health (NIH) campus to have a screening evaluation which will include physical exam, review of medical history and current medications, blood and heart tests, imaging (X-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI) or positron emission tomography (PET) scan), and evaluation of participants veins that are used for drawing blood. If the participant is eligible for the study based on the screening evaluation, they will have a baseline evaluation prior to receiving the experimental treatment which may include additional laboratory or imaging tests. Participants will have a large intravenous (IV) catheter

Primary Outcome

The MTD is the highest dose at which \< 1 of 6 participants experienced a DLT or the highest dose level studied if 2 DLTs are not observed at any of the dose levels. A DLT is all grade 3 and greater toxicities related to cell infusion, with the exception of: Cytokine Release Syndrome (CRS) that resolves \< grade 2 within 14 days of the last dose of aldesleukin; Autoimmune toxicity that resolves \< grade 2 within 14 days from starting symptoms treatment (e.g. steroids); Cardiac, gastrointestinal,

Interventions

• DRUG Cyclophosphamide
• DRUG Fludarabine
• DIAGNOSTIC_TEST EKG
• DRUG IL-2 (Aldesleukin)
• BIOLOGICAL KK-LC-1 TCR