Trial Title:
KK-LC-1 TCR-T Cell Therapy for Gastric, Breast, Cervical, and Lung Cancer
NCT ID:
NCT05483491
Condition:
Gastric Cancer
Breast Cancer
Cervical Cancer
Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Uterine Cervical Neoplasms
Aldesleukin
Conditions: 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
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
KK-LC-1 TCR-T cells
Description:
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.
Arm group label:
KK-LC-1 TCR-T cells
Other name:
KK-LC-1 TCR
Other name:
TIL
Other name:
Adoptive cell transfer
Other name:
CAR-T
Other name:
TCR
Intervention type:
Drug
Intervention name:
Aldesleukin
Description:
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.
Arm group label:
KK-LC-1 TCR-T cells
Other name:
Proleukin
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.
Detailed description:
This study will determine the MTD of KK-LC-1 TCR-T cells for the treatment of metastatic
cancers that express KK-LC-1 and will assess clinical tumor response to treatment.
KK-LC-1 is an abnormal protein that is expressed by certain types of cancer. The cancers
that most commonly express KK-LC-1 include gastric, lung, breast, and cervix cancer.
KK-LC-1 TCR-T cells are autologous T cells that are genetically engineered to target the
KK-LC-1 antigen. Tumor targeting by the KK-LC-1 TCR requires that subjects have the the
HLA-A*01:01 allele. Participants will receive a conditioning regimen consisting of
cyclophosphamide and fludarabine. They will then receive a single infusion of KK-LC-1
TCR-T cells, which will be followed by administration of aldesleukin. Adverse events,
dose limiting toxicity, tumor response, and tumor response duration will be determined.
Criteria for eligibility:
Criteria:
1. Inclusion Criteria: Subjects must meet all the following criteria to participate in
this study.
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.
Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from
participation in this study:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Rutgers Cancer Institute of New Jersey
Address:
City:
New Brunswick
Zip:
08901
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tobi Adewale
Phone:
732-710-2406
Email:
olutobi@cinj.rutgers.edu
Facility:
Name:
RWJBarnabas Health - Robert Wood Johnson University Hospital
Address:
City:
New Brunswick
Zip:
08901
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tobi Adewale
Phone:
732-710-2406
Email:
olutobi@cinj.rutgers.edu
Start date:
September 26, 2022
Completion date:
December 31, 2028
Lead sponsor:
Agency:
Christian Hinrichs
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Collaborator:
Agency:
Iovance Biotherapeutics, Inc.
Agency class:
Industry
Source:
Rutgers, The State University of New Jersey
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05483491