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

NCT05035407 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 10000045000045-C
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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....

Conditions

Kita-kyushu Lung Cancer Antigen 1, Human

Keywords

Vaccine; Gene Therapy; Cell Therapy; T Cell Therapy; Immunotherapy; CAR T; Tumor infiltrating lymphocyte; Triple Negative Breast Cancer; Metastatic Solid Tumor; Metastatic carcinoma

Outcome Measures

Primary Outcomes (2)

• Maximally Tolerated Dose (MTD) of Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T Cell Receptor (TCR) T Cells Plus Aldesleukin for the Treatment of KK-LC-1 Plus Cancers

  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, dermatological, hepatic, pulmonary, renal, hematologic, neurologic toxicity, or toxicity specified in the protocol attributable to aldesleukin that resolves to grade 2 within 14 days of the last dose of aldesleukin; and Transient grade 3 hypoxia associated with cell infusion that corrects to \< grade 2 with supplemental oxygen and/or that resolves to \< grade 2 within 24 hours; and Hemorrhage due to underlying cancer or prior radiotherapy.

  3 months

• Proportion of Participants Who Experience a Dose Limiting Toxicity (DLT) With the Number and Grade of Each Type of DLT

  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, dermatological, hepatic, pulmonary, renal, hematologic, neurologic toxicity, or toxicity specified in the protocol attributable to aldesleukin that resolves to grade 2 within 14 days of the last dose of aldesleukin; and Transient grade 3 hypoxia associated with cell infusion that corrects to \< grade 2 with supplemental oxygen and/or that resolves to \< grade 2 within 24 hours; and Hemorrhage due to underlying cancer or prior radiotherapy. Toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.

  At the time of cell infusion, up to 30 days after cell infusion

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Adverse events (AEs) will be documented from the start date of chemotherapy through 40 days after the cell administration. Beyond 40days after the cells were administered, only AEs which are serious & related to the study intervention need to be recorded.

Study Arms (1)

Treatment at Dose Levels 1 through 6

EXPERIMENTAL

Non-myeloablative, lymphocyte depleting preparative regimen, followed by Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptors (TCRs) T cells plus aldesleukin at escalating doses

Drug: IL-2 (Aldesleukin); Drug: Cyclophosphamide; Biological: KK-LC-1 TCR; Drug: Fludarabine; Diagnostic Test: EKG; Diagnostic Test: CXR; Diagnostic Test: CT; Diagnostic Test: MRI; Diagnostic Test: PET; Procedure: Biopsy; Drug: Acetaminophen; Drug: Ondansetron; Drug: Meperidine; Drug: Indomethacin; Drug: Famotidine

Interventions

IL-2 (Aldesleukin) DRUG

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).

Also known as: Interleukin-2 (Aldesleukin)

Treatment at Dose Levels 1 through 6

Cyclophosphamide DRUG

30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5)

Also known as: Cytoxan

Treatment at Dose Levels 1 through 6

KK-LC-1 TCR BIOLOGICAL

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.

Also known as: Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor

Treatment at Dose Levels 1 through 6

Fludarabine DRUG

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).

Also known as: Fludara

Treatment at Dose Levels 1 through 6

EKG DIAGNOSTIC_TEST

At screening/baseline.

Also known as: Electrocardiogram

Treatment at Dose Levels 1 through 6

CXR DIAGNOSTIC_TEST

At screening/baseline.

Also known as: Chest x-ray

Treatment at Dose Levels 1 through 6

CT DIAGNOSTIC_TEST

At screening/baseline.

Also known as: Computed tomography

Treatment at Dose Levels 1 through 6

MRI DIAGNOSTIC_TEST

At screening/baseline

Also known as: Magnetic resonance imaging

Treatment at Dose Levels 1 through 6

PET DIAGNOSTIC_TEST

At screening/baseline.

Also known as: Positron emission tomography

Treatment at Dose Levels 1 through 6

Biopsy PROCEDURE

Optional. At screening/baseline. And (+/- 48 hours) prior to start of chemo, at the first response assessment visit and at time of progression.

Also known as: Bx

Treatment at Dose Levels 1 through 6

Acetaminophen DRUG

650mg every(q) 4 hours for supportive therapy as needed.

Also known as: Tylenol, Panadol

Treatment at Dose Levels 1 through 6

Ondansetron DRUG

0.15mg/kg/dose intravenous every(q) 8 hours for nausea and vomiting.

Also known as: Zofran, Zofran ODT, Zuplenz

Treatment at Dose Levels 1 through 6

Meperidine DRUG

25-50mg intravenous for severe chilling if needed.

Also known as: Demerol

Treatment at Dose Levels 1 through 6

Indomethacin DRUG

50-75mg every(q) 8 hours for supportive therapy as needed.

Also known as: Tivorbex, Indocin

Treatment at Dose Levels 1 through 6

Famotidine DRUG

20mg every(q) 12 hours for supportive therapy as needed.

Also known as: Pepcid, Acid reducer, Acid controller

Treatment at Dose Levels 1 through 6

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) positive epithelial cancer (KK-LC-1 positivity assay performed at Rutgers Cancer Institute of New Jersey). KK-LC-1 expression will be determined by immunohistochemistry (IHC). KK-LC- 1 score of 25% or greater will be considered positive.
• Participants must be HLA-A 01 (human leukocyte antigen serotype within HLA-A "A" serotype group) by low resolution typing, and HLA-A 01:01 by one of the high-resolution type results
• Measurable metastatic or refractory/recurrent KK-LC-1+ epithelial cancer (determined by Immunohistochemistry (IHC).
• All participants must have received prior first line standard therapy or be ineligible to receive available therapies with known survival benefit.
• Participants with three or fewer brain metastases that have been treated with surgery or stereotactic radiosurgery are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month before protocol treatment. Participants with surgically resected brain metastases are eligible.
• Age \>18 years of age. Because no dosing or adverse event data are currently available on the use of KK-LC-1 T cell receptor (TCR) in participants \<18 years of age, children are excluded from this study.
• Eastern Cooperative Oncology Group (ECOG) performance status \<1.
• Participants must have adequate organ and marrow function as defined below:
• leukocytes \>=3,000/mcL
• absolute neutrophil count \>=1,500/mcL
• platelets \>=100,000/mcL
• hemoglobin \>=9.0 g/dL
• total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) =\<2.5 X institutional upper limit of normal
• creatinine within normal institutional limits

You may not qualify if:

• Participants who are receiving any other investigational agents.
• History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine or aldesleukin.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Participants with abnormal pulmonary function tests but stable obstructive or restrictive pulmonary disease may be eligible.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
• Participants on active systemic immunosuppressive therapy that cannot be safely withheld.
• Participants with a history of coronary revascularization or ischemic symptoms unless participant has a normal cardiac stress test.
• Any condition which would, in the opinion of the Principal Investigator, indicate that the subject is a poor candidate for the clinical trial or would jeopardize the subject or the integrity of the data obtained.
• Documented left ventricular ejection fraction (LVEF) \<= 45%

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Neoplasm Metastasis; Carcinoma

Interventions

Interleukin-2; aldesleukin; Cyclophosphamide; fludarabine; fludarabine phosphate; Electrocardiography; Diagnostic Imaging; Tomography, X-Ray Computed; Magnetic Resonance Imaging; Positron-Emission Tomography; Biopsy; Acetaminophen; Ondansetron; Meperidine; Indomethacin; Famotidine

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Image Interpretation, Computer-Assisted; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Tomography; Tomography, Emission-Computed; Radionuclide Imaging; Diagnostic Techniques, Radioisotope; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Isonipecotic Acids; Acids, Heterocyclic; Piperidines; Thiazoles; Sulfur Compounds

Results Point of Contact

• Title: Dr. Scott Norberg
• Organization: National Cancer Institute

scoot.norberg@nih.gov

301-275-9668

Study Officials

• Scott M Norberg, D.O.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 3, 2021
• First Posted: September 5, 2021
• Study Start: March 8, 2022
• Primary Completion: July 16, 2025
• Study Completion: July 16, 2025
• Last Updated: December 2, 2025
• Results First Posted: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)