Autologous CAR-T Cells Targeting B7-H3 in PDAC

Official title

A Phase I Study of Autologous CAR-T Cells Targeting the B7-H3 Antigen and Containing the Inducible Caspase 9 Safety Switch in Subjects With Refractory Pancreatic Ductal Adenocarcinoma (PDAC)

Overview

The purpose of this gene therapy research study is to test the safety and tolerability of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells against the B7-H3 antigen (iC9.CAR.B7-H3 T cells) in patients with pancreatic ductal adenocarcinoma that came back after receiving standard therapy for this cancer. The iC9.CAR.B7-H3 treatment is experimental and has not been approved by the Food and Drug Administration.

Detailed description

This is a phase 1, single-center, open-label study to determine the safety of escalating doses of chimeric antigen receptor T cells (CAR-T) cells targeting the B7-H3 antigen and containing the inducible caspase 9 safety switch (iC9-CAR.B7-H3 T cells) administered to adult subjects with refractory pancreatic ductal adenocarcinoma. The safety of iC9-CAR.B7-H3 T cells will be investigated using a modified 3+3 design with a starting dose of 1 × 106 transduced cells/kg. The data from the dose escalation will be used to determine a recommended phase 2 dose, which will be decided based on the maximum tolerated dose and additional factors such as the ability to manufacture sufficient cells for infusion.

The body has different ways of fighting cancer and other diseases; however, no single way seems perfect. The experimental treatment in this study combines two different ways the body fights cancer, and they are antibodies and T cells. Antibodies are proteins that protect the body from foreign invaders like bacteria. Antibodies work by attaching to these bacteria or substances, which stops them from growing and causing bad effects. T cells are special infection-fighting blood cells that can kill viruses and other cells, including tumor cells. Antibodies and T cells have been used to treat patients with cancer. They both have shown promise, but neither alone has been able to cure most patients. The treatment that is being studied in this study is called autologous T lymphocyte chimeric antigen receptor cells targeted against the B7-H3 antigen and containing inducible caspase 9 safety switch (iC9). The short name for this treatment is iC9.CAR.B7-H3 T cells. For the rest of this consent, we will refer to the iC9.CAR.B7-H3 T cells as the modified CAR-T cells for ease of reading this consent.

Interventions

• Biological iC9-CAR.B7-H3 T cell infusion
  iC9-CAR.B7-H3 T cell product will be administered via intravenous injection over 5 - 10 minutes.

Primary outcome measures

• Number of participants with adverse event [Time frame: Up to 4 weeks]
• Cytokine Release Syndrome [Time frame: Up to 4 weeks]
• Neurotoxicity [Time frame: Up to 4 weeks]

Secondary outcome measures (8)

• Definition of Dose Limiting Toxicity [Time frame: Up to 4 weeks]
• Progression Free Survival (PFS) [Time frame: Up to 2 years]
• Overall Survival (OS) [Time frame: Up to 2 years]
• The disease control rate (DCR) [Time frame: Up to 2 years]
• B7-H3 expression [Time frame: Up to 18 months]
• The proportion of subjects who were able to receive CAR-T cell infusion [Time frame: Up to 18 months]
• Objective response rate (ORR)- bridging therapy [Time frame: Up to 2 years]
• Objective response rate- no bridging therapy [Time frame: Up to 2 years]

Eligibility criteria

Inclusion criteria

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for releasing personal health information explained to, understood by, and signed by the subject or legally authorized representative.
• Age ≥ 18 years at the time of consent.
• Eastern Cooperative Oncology Group of 0-1 Performance Status)
• Histological or cytological evidence/confirmation of pancreatic ductal adenocarcinoma.
• Female subjects of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after study treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets < 1% failure rate for protection from pregnancy in the product label.
• Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 3 months after the cell infusion therapy.

Exclusion criteria

• Subjects with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
• Subject is not willing and able to comply with study procedures based on the judgment of the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center — Chapel Hill

Identifiers

NCT: NCT06158139 · LCCC2223-ATL

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗