NCT05035407

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

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

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

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 inserted into a vein to undergo a procedure called leukapheresis. Leukapheresis is the removal of the blood by a machine to collect specific white blood cells. The remaining blood is returned to the body. This procedure is needed to collect the cells that will be modified to target the cancer. The cells are grown in the lab and given back to the participant through an injection into the participant's tumor. It takes 11-15 days to grow the cells. While the cells are growing, the participant will be admitted to the hospital about one week before the cell infusion to receive 2 types of chemotherapy through an IV catheter over 5 days. The main purpose of the chemotherapy is to make the cells more effective in fighting the cancer tumors. The cells will be given 1-2 days after the last dose of chemotherapy. Within 24 hours after the cell infusion, participants will be given a cell growth factor called aldesleukin through an IV for up to 4 days. Aldesleukin is thought to help the cells live longer in the participant's body. Participants will recover in the hospital until they are well enough to go home, which is usually about 7-12 days after the cell infusion or last dose of aldesleukin. Participants will have a follow-up visit at approximately 40 days after the date of cell infusion. This visit will be to evaluate the safety of the cell therapy and the response of the cancer to the treatment which will include physical examination, lab tests, and imaging studies. If a participant has stable disease or their cancer has responded to the treatment, they will be seen again at 12 weeks post cell infusion, every 3 months x 3 visits, and then every 6 months x 5 years. If a participants cancer progresses after this therapy, they will be return to their home doctor for further management. After receiving cell therapy, participants will be followed on a long-term gene therapy protocol. Participants will have blood drawn periodically to test if the cells have grown or changed. These blood tests will take place immediately before the cells, and then at 3, 6, and 12 months for the first year and possibly annually thereafter based on the results. These tests can be drawn locally and sent to the NIH. After a participant is off the study, they will be contacted by telephone or mailed questionnaire for a total of 15 years after cell therapy....

Detailed description

Background: Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) is a cancer germline (CG) antigen with expression restricted to germ cells (which lack major histocompatibility complex (MHC) class I expression) in adults and epithelial cancers including lung, breast and gastric. This limited expression pattern makes it an ideal target for T Cell Receptor (TCR) gene therapy. TCR T cell therapy targeting CG antigens has been shown to induce objective responses without autoimmunity or off-target toxicity in participants with melanoma, synovial sarcoma and cervical cancer. T cells genetically engineered with a TCR targeting KK-LC-1 display specific reactivity against HLA-A01:01 (human leukocyte antigen serotype within HLA-A "A" serotype group), KK-LC-1 target cells. KK-LC-1 TCR T cells can mediate tumor regression in pre-clinical mouse models of cancer. Objective: To determine the maximally tolerated dose of KK-LC-1 TCR T cells plus aldesleukin for the treatment of metastatic KK-LC-1 positive epithelial cancers. Eligibility: Participants greater than or equal to 18 years old with metastatic or refractory/recurrent KK-LC-1 positive epithelial cancer. Prior first line systemic therapy is required unless the participant declines standard treatment. Participants must be HLA-A-01:01-positive. Design: This is a phase I clinical trial that will test the safety and efficacy of escalating doses of KK-LC-1 TCR T cells. Participants will receive a non-myeloablative lymphocyte-depleting preparative regimen of cyclophosphamide and fludarabine followed by a single infusion of KK-LC-1 TCR T cells and high-dose aldesleukin. Re-treatment will be allowed for a small number of subjects.

Conditions

• Kita-kyushu Lung Cancer Antigen 1, Human

Interventions

Type	Name	Description
DRUG	IL-2 (Aldesleukin)	Dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period beginning within 24 hours of cell infusion and continuing for up to four days (maximum 12 doses).
DRUG	Cyclophosphamide	30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5)
BIOLOGICAL	KK-LC-1 TCR	Transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells in escalating doses. Dose Level 1: 1 x 10\^8 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Dose Level 2: 5 x 10\^8 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Dose Level 3: 1 x 10\^9 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Dose Level 4: 5 x 10\^9 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Dose Level 5: 1 x 10\^10 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Dose Level 6: 6 x 10\^10 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells.
DRUG	Fludarabine	25 mg/m\^2 intravenous (IV) infusion over 30 minutes (+ 10 min) to be administered following completion of cyclophosphamide. Once daily x 5 doses (Days -6, -5, -4, -3, -2).
DIAGNOSTIC_TEST	EKG	At screening/baseline.
DIAGNOSTIC_TEST	CXR	At screening/baseline.
DIAGNOSTIC_TEST	CT	At screening/baseline.
DIAGNOSTIC_TEST	MRI	At screening/baseline
DIAGNOSTIC_TEST	PET	At screening/baseline.
PROCEDURE	Biopsy	Optional. At screening/baseline. And (+/- 48 hours) prior to start of chemo, at the first response assessment visit and at time of progression.
DRUG	Acetaminophen	650mg every(q) 4 hours for supportive therapy as needed.
DRUG	Ondansetron	0.15mg/kg/dose intravenous every(q) 8 hours for nausea and vomiting.
DRUG	Meperidine	25-50mg intravenous for severe chilling if needed.
DRUG	Indomethacin	50-75mg every(q) 8 hours for supportive therapy as needed.
DRUG	Famotidine	20mg every(q) 12 hours for supportive therapy as needed.

Timeline

• Start date: 2022-03-08
• Primary completion: 2025-07-16
• Completion: 2025-07-16
• First posted: 2021-09-05
• Last updated: 2025-12-02
• Results posted: 2025-12-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study