Clinical trial NCT05620342: Autologous CAR T-Cells Targeting the GD2 Antigen for Lung Cancer
Official title: Administration of T Cells Expressing a 2nd Generation GD2 Chimeric Antigen Receptor, IL-15, and iCaspase9 Safety Switch in Subjects With Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Lung Cancer
Small Cell Lung Carcinoma
Non Small Cell Lung Cancer
Keywords: cellular therapy
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Bellicum Pharmaceuticals
name: United States Department of Defense
First posted: 2022-11-17
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase 1, single-center, open-label study that enrolls adult subjects with extensive stage lung cancer or stage IV non-small cell lung cancer that is platinum-refractory and received PD-1 and/or PD-L1 therapy. The purpose of this study is to test the safety of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells against the GD2 antigen (iC9-GD2.CAR.IL-15 T cells) in subjects with lung cancer. How much (dose) of the iC9-GD2.CAR.IL-15 T cells are safe to use without causing too many side effects and what is the maximum dose that could be tolerated will be studied.

Modified immune cells as an experimental treatment that combines antibodies and T cells will be used. Antibodies are proteins that protect the body from foreign invaders like bacteria. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill viruses and other cells, including tumor cells. Although antibodies and T cells have been used to treat cancer and they both have shown promise, neither alone has been able to cure most patients. This study will combine T cells and antibodies to create a more effective treatment.

The treatment that is being researched in this study is called autologous T lymphocyte chimeric antigen receptor cells targeted against the disialoganglioside (GD2) antigen that expresses Interleukin (IL)-15, and the inducible caspase 9 safety switch (iC9). The short name for this treatment is iC9.GD2.CAR.IL-15 T cells therapy is an experimental therapy and has not been approved by the Food and Drug Administration. There are two steps. In the first step, blood will be collected from the subjects to prepare the iC9-GD2.CAR.IL-15 T cells. T cells will be isolated from the blood and modified to make iC9-GD2.CAR.IL-15. In the second step, the iC9-GD2.CAR.IL-15 T cells produced from the subject's own blood will be administered to the subject.


Eligibility criteria: Inclusion Criteria:

1. Written informed consent to undergo cell procurement explained to, understood by, and signed by the subject.
2. Subject has a life expectancy of ≥ 12 weeks.
3. Subject must be platinum-refractory and either currently receiving or has previously received a PD1/PDL1 inhibitor
4. Use of systemic corticosteroids at doses ≥10 mg prednisone daily or it's equivalent; those receiving \<10 mg daily may be enrolled at the discretion of the investigator.
5. Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to cell procurement.
6. Subject has demonstrated adequate organ function.

Exclusion Criteria:

1 . Subject has less than 12 weeks of life expectancy.

2. Subject did not receive platinum-based chemotherapy

3. Subject does not have adequate organ function.

Primary outcomes:
measure: Number of participants with adverse event
timeFrame: Up to 4 weeks
measure: Cytokine Release Syndrome (CRS)
timeFrame: Up to 4 weeks
measure: Neurotoxicity
timeFrame: Up to 4 weeks
Secondary outcomes:
measure: Identification of Recommended phase 2 dose (RP2D)
timeFrame: Up to 4 weeks
measure: Overall Response Rate (ORR)
timeFrame: Up to 4 weeks
measure: Progression Free Survival (PFS)
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Duration of Response (DOR)
timeFrame: Up to 2 years
measure: Duration of Benefit
timeFrame: Up to 2 years
measure: Disialoganglioside (GD2) Expression
timeFrame: Baseline
measure: Disialoganglioside Expression and tumor response rate correlations
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: jared_weiss@med.unc.edu
name: Jared Weiss
role: PRINCIPAL_INVESTIGATOR
References: