Kita-kyushu Lung Cancer Antigen 1, HumanPhase 1NCT05035407
T Cell Receptor Gene Therapy Targeting KK-LC-1 for Gastric, Breast, Cervical, Lung and Other KK-LC-1 Positive Epithelial Cancers
A Phase 1 study testing IL-2 (Aldesleukin), Cyclophosphamide and KK-LC-1 TCR in people with Kita-kyushu Lung Cancer Antigen 1, Human, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Kita-kyushu Lung Cancer Antigen 1, Human
- What is being tested?
- IL-2 (Aldesleukin), Cyclophosphamide and KK-LC-1 TCR
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Mar 2022to 16 Jul 2025
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- OR
- creatinine clearance >=60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal.
- -Serology:
- Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who are HIV seropositive can have decreased immune-competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.)
- Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then the participant must be tested for the presence of antigen by reverse transcription-polymerase chain reaction (RT-PCR) and be hepatitis C virus ribonucleic acid (HCV RNA) negative.
- The effects of the study agent on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, individuals of child-bearing potential and their partners must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and up to twelve (12) months after treatment. Individuals of childbearing potential must have a negative pregnancy test. Individuals of childbearing potential are defined as all individuals except individuals who are postmenopausal or who have had a hysterectomy. Postmenopausal will be defined as individuals over the age of 55 who have not had a menstrual period in at least one year or a participant that has received a treatment (i.e., chemotherapy or pelvic radiation) that has resulted in them becoming postmenopausal. Should an individual become pregnant or suspect pregnancy while individuals or partner is participating in this study, individuals should inform treating physician immediately.
- Because there is a potential risk for adverse events in nursing infant's secondary to treatment of the mother with KK-LC-1 TCR transduced peripheral blood lymphocytes (PBLs), breastfeeding should be discontinued if the mother is treated with KK-LC-1 TCR transduced PBL. These potential risks may also apply to other agents used in this study.
- More than four weeks must have elapsed since any prior systemic therapy at the time the participant receives the KK-LC-1 TCR T cells.
- Participants may have undergone minor surgical procedures within the past three weeks, as long as all toxicities have recovered to Grade 1 or less
- Ability of subject to understand and the willingness to sign a written informed consent document.
Who cannot join
- 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 with autoimmune diseases such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis or pancreatitis, and systemic lupus rythematosus. Hypothyroidism, vitiligo and other minor autoimmune disorders are not exclusionary.
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- 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%
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: 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
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.
Read more
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....
Read the 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
- Being tested
- IL-2 (Aldesleukin), Cyclophosphamide, KK-LC-1 TCR, Fludarabine, EKG
- Keywords
- Vaccine, Gene Therapy, Cell Therapy, T Cell Therapy, Immunotherapy, CAR T, Tumor infiltrating lymphocyte, Triple Negative Breast Cancer, Metastatic Solid Tumor, Metastatic carcinoma
- Medical subject headings
- Triple Negative Breast Neoplasms, Neoplasm Metastasis, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IL-2 (Aldesleukin)Drug
Also called Interleukin-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).
CyclophosphamideDrug
Also called Cytoxan
30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5)
KK-LC-1 TCRBiological
Also called Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor
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.
FludarabineDrug
Also called Fludara
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).
EKGDiagnostic test
Also called Electrocardiogram
At screening/baseline.
CXRDiagnostic test
Also called Chest x-ray
At screening/baseline.
CTDiagnostic test
Also called Computed tomography
At screening/baseline.
MRIDiagnostic test
Also called Magnetic resonance imaging
At screening/baseline
PETDiagnostic test
Also called Positron emission tomography
At screening/baseline.
BiopsyProcedure or surgery
Also called Bx
Optional. At screening/baseline. And (+/- 48 hours) prior to start of chemo, at the first response assessment visit and at time of progression.
AcetaminophenDrug
Also called Tylenol, Panadol
650mg every(q) 4 hours for supportive therapy as needed.
OndansetronDrug
Also called Zofran, Zofran ODT, Zuplenz
0.15mg/kg/dose intravenous every(q) 8 hours for nausea and vomiting.
MeperidineDrug
Also called Demerol
25-50mg intravenous for severe chilling if needed.
IndomethacinDrug
Also called Tivorbex, Indocin
50-75mg every(q) 8 hours for supportive therapy as needed.
FamotidineDrug
Also called Pepcid, Acid reducer, Acid controller
20mg every(q) 12 hours for supportive therapy as needed.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: At the time of cell infusion, up to 30 days after cell infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2021
- Study start8 Mar 2022
- Primary completion16 Jul 2025
- Study completion16 Jul 2025
Why it stopped: Site plans to become a site for a multicenter study of this therapy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Kita-kyushu Lung Cancer Antigen 1, HumanStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Scott Norberg, D.O., National Cancer Institute (NCI)
- Investigators
- Scott M Norberg, D.O., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05035407
- Sponsor's protocol ID
- 10000045
- Other IDs
- 000045-C
- Status last verified
- Nov 2025
- First submitted
- 3 Sep 2021
- Last updated
- 2 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05035407
- Acronym / sponsor ID
- 10000045
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Site plans to become a site for a multicenter study of this therapy
- Enrolment
- 36 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 8 Mar 2022 (actual)
- Primary completion
- 16 Jul 2025 (actual)
- Study completion
- 16 Jul 2025 (actual)
- First posted
- 5 Sep 2021 (actual)
- Results
- Posted 2 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment at Dose Levels 1 through 6 | Experimental | 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: FamotidineNon-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 |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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.
Key exclusion criteria (10 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IL-2 (Aldesleukin)Also: Interleukin-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 | Treatment at Dose Levels 1 through 6 |
| CyclophosphamideAlso: Cytoxan30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5) | Drug | Treatment at Dose Levels 1 through 6 |
| KK-LC-1 TCRAlso: Kita-Kyushu Lung Cancer Antigen-1 T-Cell ReceptorTransduced 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. | Biological | Treatment at Dose Levels 1 through 6 |
| FludarabineAlso: Fludara25 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). | Drug | Treatment at Dose Levels 1 through 6 |
| EKGAlso: ElectrocardiogramAt screening/baseline. | Diagnostic test | Treatment at Dose Levels 1 through 6 |
| CXRAlso: Chest x-rayAt screening/baseline. | Diagnostic test | Treatment at Dose Levels 1 through 6 |
| CTAlso: Computed tomographyAt screening/baseline. | Diagnostic test | Treatment at Dose Levels 1 through 6 |
| MRIAlso: Magnetic resonance imagingAt screening/baseline | Diagnostic test | Treatment at Dose Levels 1 through 6 |
| PETAlso: Positron emission tomographyAt screening/baseline. | Diagnostic test | Treatment at Dose Levels 1 through 6 |
| BiopsyAlso: BxOptional. At screening/baseline. And (+/- 48 hours) prior to start of chemo, at the first response assessment visit and at time of progression. | Procedure or surgery | Treatment at Dose Levels 1 through 6 |
| AcetaminophenAlso: Tylenol, Panadol650mg every(q) 4 hours for supportive therapy as needed. | Drug | Treatment at Dose Levels 1 through 6 |
| OndansetronAlso: Zofran, Zofran ODT, Zuplenz0.15mg/kg/dose intravenous every(q) 8 hours for nausea and vomiting. | Drug | Treatment at Dose Levels 1 through 6 |
| MeperidineAlso: Demerol25-50mg intravenous for severe chilling if needed. | Drug | Treatment at Dose Levels 1 through 6 |
| IndomethacinAlso: Tivorbex, Indocin50-75mg every(q) 8 hours for supportive therapy as needed. | Drug | Treatment at Dose Levels 1 through 6 |
| FamotidineAlso: Pepcid, Acid reducer, Acid controller20mg every(q) 12 hours for supportive therapy as needed. | Drug | Treatment at Dose Levels 1 through 6 |
Primary outcome
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
Time frame: 3 months
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.
Proportion of Participants Who Experience a Dose Limiting Toxicity (DLT) With the Number and Grade of Each Type of DLT
Time frame: At the time of cell infusion, up to 30 days after cell infusion
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott M Norberg, D.O. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IL-2 (Aldesleukin), Cyclophosphamide and KK-LC-1 TCR in people with Kita-kyushu Lung Cancer Antigen 1, Human, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2025.