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

NCT05483491 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 192004NCI-2022-07699Pro2022002198
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Gastric Cancer; Breast Cancer; Cervical Cancer; Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of KK-LC-1 TCR-T cells

  The highest dose level achieved according to the protocol-defined criteria for DLTs and determination of MTD.

  30 days

Secondary Outcomes (3)

• Adverse events of KK-LC-1 TCR T cells

  30 days

• Tumor response rate

  6 weeks

• Tumor response duration

  Through study completion, up to 5 years

Study Arms (1)

KK-LC-1 TCR-T cells

EXPERIMENTAL

Subjects will receive a conditioning regimen, KK-LC-1 TCR-T cells, and aldesleukin.

Biological: KK-LC-1 TCR-T cells; Drug: Aldesleukin

Interventions

KK-LC-1 TCR-T cells BIOLOGICAL

Participants will receive a conditioning regimen consisting of cyclophosphamide and fludarabine. KK-LC-1 TCR-T cells will be administered as a single intravenous infusion.

Also known as: KK-LC-1 TCR, TIL, Adoptive cell transfer, CAR-T, TCR

KK-LC-1 TCR-T cells

Aldesleukin DRUG

Aldesleukin 720,000 IU/kg IV every 8 hours will be preferentially administered as an inpatient within 24 hours after KK-LC-1 TCR-T cell infusion for up to 6 doses; however up to 24 hours may elapse between doses. Aldesleukin dosing will be stopped for aldesleukin-related grade 3 or greater toxicity other than flushing, fever, chills, or hemodynamic changes (tachycardia or hypotension) that respond to crystalloid infusion. Aldesleukin may also be stopped at any time at investigator discretion.

Also known as: Proleukin

KK-LC-1 TCR-T cells

Eligibility Criteria

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

You may qualify if:

• Signed, written informed consent obtained prior to any study procedures.
• Age \> 18 years at the time of informed consent.
• 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.
• HLA-A\*01:01 allele by HLA haplotype test.
• Measurable disease per RECIST Criteria Version 1.1 at time of enrollment.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
• 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.
• 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.
• Participants must have 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

You may not qualify if:

• Current treatment with another investigational agent.
• History of severe allergic reactions to compounds of similar chemical or biologic composition to agents in used in study.
• 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.
• 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.
• 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.
• Participants on immunosuppressive drugs including corticosteroids unless meeting criteria outlined in Section 6.1 (Prohibited Medications).
• 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.
• 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.
• 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:
• Carcinoma in situ
• Cutaneous skin cancers requiring only local excision
• Low grade non-muscle invasive bladder cancer
• Low grade prostate cancer Participants with prior or concurrent malignancy that do not meet the above criteria are excluded.
• Subjects who received a live vaccine within 30 days prior to enrollment are not eligible.
• 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.

Sponsors & Collaborators

• Christian Hinrichs: lead
• National Cancer Institute (NCI): collaborator
• Iovance Biotherapeutics, Inc.: collaborator

Study Sites (2)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

RECRUITING

RWJBarnabas Health - Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08901, United States

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Breast Neoplasms; Uterine Cervical Neoplasms; Lung Neoplasms

Interventions

Adoptive Transfer; aldesleukin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Christian S Hinrichs, MD

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tobi Adewale

CONTACT

732-710-2406; olutobi@cinj.rutgers.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Section of Cancer Immunotherapy

Model Details: This is a phase I clinical trial that will determine the maximum tolerated dose and clinical tumor responses for escalating doses of KK-LC-1 TCR-T cells.

Study Record Dates

• First Submitted: July 20, 2022
• First Posted: August 2, 2022
• Study Start: September 26, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: Data will be made available through the publisher at the time of publication.
• Access Criteria: Data will be accessible through the publisher.

Locations

US (2)