RECRUITING

KK-LC-1 TCR-T Cell Therapy for Gastric, Breast, Cervical, and Lung Cancer

Conditions

Gastric Cancer Breast Cancer Cervical Cancer Lung Cancer CAR-T immunotherapy TIL stomach cancer triple negative cell therapy gene therapy tumor infiltrating lymphocytes T cells immune

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2022-09-26

Study Completion:2028-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05483491

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
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. Measurable disease per RECIST Criteria Version 1.1 at time of enrollment. 6. Prior treatment with cancer type-specific standard of care systemic cancer therapy is required. Standard treatment options must be considered and declined. Documentation of rationale is required if a subject is deemed unsuitable for standard therapy. 7. Subjects with \< 3 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. Patients with surgically resected brain metastases are eligible. 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening. 9. Negative pregnancy test for women under 55 and all women who have had a menstrual period in the last 12 months. A pregnancy tests is not required for women who have had a bilateral oophorectomy or hysterectomy. 10. Women of child-bearing potential must agree to use adequate contraception (i.e., intrauterine device, hormonal barrier method of birth control; abstinence; tubal ligation or vasectomy) prior to study entry and for 12 months after treatment. Should a women become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. 11. Participants must have organ and marrow function as defined below: 1. Leukocytes \> 3,000/mcL 2. Absolute neutrophil count \> 1,500/mcL 3. Platelets \> 100,000/mcL 4. Hemoglobin \> 9.0 g/dL 5. Total bilirubin within normal institutional limits except in participants with Gilbert's Syndrome who must have a total bilirubin \< 3.0 mg/dL. 6. Serum AST (SGOT)/ALT (SGPT) \< 2.5 x ULN 7. Calculated creatinine clearance (CrCl) \>50 mL/min/1.73 m2for participants with creatinine levels above institutional normal (by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation). 8. INR or a PTT ≤1.5 X ULN unless the subject is receiving anticoagulant therapy. Subjects on anticoagulant therapy must have a PT or PTT within therapeutic range and no history of severe hemorrhage. 12. Serology: HIV antibody negative * Hepatitis B antigen negative * Hepatitis C antibody negative or HCV RNC negative (i.e., no current HCV infection) 13. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the KK-LC-1 TCR T cells. Adverse events from prior therapy must have resolved to ≤ grade 1 according to CTCAE Version 5.0 or have demonstrated clinical stability and meet the eligibility criteria for the protocol. 14. Oxygen saturation ≥ 92% on room air. 15. Left ventricular ejection fraction ≥45% by echocardiogram or MUGA for patients 50 years of age or older.	1. Current treatment with another investigational agent. 2. History of severe allergic reactions to compounds of similar chemical or biologic composition to agents in used in study. 3. Uncontrolled intercurrent illness such as active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations at the time of treatment that would limit compliance with study requirements. 4. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with KK-LC-1 TCR T cells, breastfeeding should be discontinued if the mother is treated with KK-LC-1 TCR cells. The potential risks may also apply to other agents used in this study. 5. Participants with a systemic immunodeficiency including acquired deficiency such as HIV or primary immunodeficiency such as Severe Combined Immunodeficiency Disease are ineligible. 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 treatment. 6. Participants on immunosuppressive drugs including corticosteroids unless meeting criteria outlined in Section 6.1 (Prohibited Medications). 7. Subjects with HLA-A\*01:01 damaging mutation or allele loss or other molecular resistance detected by clinical or research genomic profiling will not be eligible. 8. Participants with potentially severe autoimmune diseases such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis, autoimmune pancreatitis, or systemic lupus erythematosus are not eligible. Patients with less severe autoimmune diseases such as hypothyroidism, vitiligo, and other minor autoimmune disorders are eligible. 9. Participants with prior or concurrent malignancy whose natural history or treatment is unlikely to interfere with the safety or efficacy assessments of the investigational regimen are eligible for this trial. Examples include, but are not limited to: 1. Carcinoma in situ 2. Cutaneous skin cancers requiring only local excision 3. Low grade non-muscle invasive bladder cancer 4. Low grade prostate cancer Participants with prior or concurrent malignancy that do not meet the above criteria are excluded. 10. Subjects who received a live vaccine within 30 days prior to enrollment are not eligible. 11. Determination by the Principal Investigator that participation is not in the best interest of the research subject or may jeopardize the safety of the subject or integrity of the clinical trial data.

Inclusion Criteria

Exclusion Criteria

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. Measurable disease per RECIST Criteria Version 1.1 at time of enrollment.
6. Prior treatment with cancer type-specific standard of care systemic cancer therapy is required. Standard treatment options must be considered and declined. Documentation of rationale is required if a subject is deemed unsuitable for standard therapy.
7. Subjects with \< 3 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. Patients with surgically resected brain metastases are eligible.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
9. Negative pregnancy test for women under 55 and all women who have had a menstrual period in the last 12 months. A pregnancy tests is not required for women who have had a bilateral oophorectomy or hysterectomy.
10. Women of child-bearing potential must agree to use adequate contraception (i.e., intrauterine device, hormonal barrier method of birth control; abstinence; tubal ligation or vasectomy) prior to study entry and for 12 months after treatment. Should a women become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
11. Participants must have organ and marrow function as defined below:
1. Leukocytes \> 3,000/mcL
2. Absolute neutrophil count \> 1,500/mcL
3. Platelets \> 100,000/mcL
4. Hemoglobin \> 9.0 g/dL
5. Total bilirubin within normal institutional limits except in participants with Gilbert's Syndrome who must have a total bilirubin \< 3.0 mg/dL.
6. Serum AST (SGOT)/ALT (SGPT) \< 2.5 x ULN
7. Calculated creatinine clearance (CrCl) \>50 mL/min/1.73 m2for participants with creatinine levels above institutional normal (by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation).
8. INR or a PTT ≤1.5 X ULN unless the subject is receiving anticoagulant therapy. Subjects on anticoagulant therapy must have a PT or PTT within therapeutic range and no history of severe hemorrhage.
12. Serology:
* HIV antibody negative
* Hepatitis B antigen negative
* Hepatitis C antibody negative or HCV RNC negative (i.e., no current HCV infection)
13. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the KK-LC-1 TCR T cells. Adverse events from prior therapy must have resolved to ≤ grade 1 according to CTCAE Version 5.0 or have demonstrated clinical stability and meet the eligibility criteria for the protocol.
14. Oxygen saturation ≥ 92% on room air.
15. Left ventricular ejection fraction ≥45% by echocardiogram or MUGA for patients 50 years of age or older.

1. Current treatment with another investigational agent.
2. History of severe allergic reactions to compounds of similar chemical or biologic composition to agents in used in study.
3. Uncontrolled intercurrent illness such as active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations at the time of treatment that would limit compliance with study requirements.
4. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with KK-LC-1 TCR T cells, breastfeeding should be discontinued if the mother is treated with KK-LC-1 TCR cells. The potential risks may also apply to other agents used in this study.
5. Participants with a systemic immunodeficiency including acquired deficiency such as HIV or primary immunodeficiency such as Severe Combined Immunodeficiency Disease are ineligible. 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 treatment.
6. Participants on immunosuppressive drugs including corticosteroids unless meeting criteria outlined in Section 6.1 (Prohibited Medications).
7. Subjects with HLA-A\*01:01 damaging mutation or allele loss or other molecular resistance detected by clinical or research genomic profiling will not be eligible.
8. Participants with potentially severe autoimmune diseases such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis, autoimmune pancreatitis, or systemic lupus erythematosus are not eligible. Patients with less severe autoimmune diseases such as hypothyroidism, vitiligo, and other minor autoimmune disorders are eligible.
9. Participants with prior or concurrent malignancy whose natural history or treatment is unlikely to interfere with the safety or efficacy assessments of the investigational regimen are eligible for this trial. Examples include, but are not limited to:
1. Carcinoma in situ
2. Cutaneous skin cancers requiring only local excision
3. Low grade non-muscle invasive bladder cancer
4. Low grade prostate cancer Participants with prior or concurrent malignancy that do not meet the above criteria are excluded.
10. Subjects who received a live vaccine within 30 days prior to enrollment are not eligible.
11. Determination by the Principal Investigator that participation is not in the best interest of the research subject or may jeopardize the safety of the subject or integrity of the clinical trial data.

Contacts and Locations

Study Contact

Tobi Adewale

CONTACT

732-710-2406

olutobi@cinj.rutgers.edu

Principal Investigator

Christian S Hinrichs, MD

PRINCIPAL_INVESTIGATOR

Rutgers Cancer Institute of New Jersey

Study Locations (Sites)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901

United States

RWJBarnabas Health - Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08901

United States

Collaborators and Investigators

Sponsor: Christian Hinrichs

Christian S Hinrichs, MD, PRINCIPAL_INVESTIGATOR, Rutgers Cancer Institute of New Jersey

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-09-26

Study Completion Date2028-12-31

Study Record Updates

Study Start Date2022-09-26

Study Completion Date2028-12-31

Terms related to this study

Keywords Provided by Researchers

CAR-T
immunotherapy
TIL
stomach cancer
lung cancer
breast cancer
triple negative
cervical cancer
cell therapy
gene therapy
tumor infiltrating lymphocytes
T cells
immune

Additional Relevant MeSH Terms

Gastric Cancer
Breast Cancer
Cervical Cancer
Lung Cancer