Autologous CAR-T Cells Targeting B7H3 in Ovarian Cancer iC9-CAR.B7-H3 T Cells

NCT06305299 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: LCCC2152-ATL
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this 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 ovarian cancer 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. The study team wants to know how much (dose) of the iC9-CAR.B7-H3 T cells are safe to use in patients without causing too many side effects and what is the maximum dose could be tolerated. There are two parts to this study. In part 1, approximately blood will be collected from subjects to prepare the iC9.CAR.B7-H3 T cells. The study team will collect disease-fighting T cells from the blood and modify them to prepare the iC9.CAR.B7-H3 T cells. In part 2, the iC9.CAR.B7-H3 T cells will be given to eligible subjects by infusion three days after completion of lymphodepletion chemotherapy.

Conditions

Recurrent; Ovary Neoplasm; Ovarian Cancer; Epithelial Ovarian Cancer

Keywords

cellular therapy; biologic therapy; Platinum Resistant

Outcome Measures

Primary Outcomes (3)

• Toxicity: NCI-CTCAE

  Toxicity will be graded as the Number of participants with adverse events (AE)s AEs will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Dose Limiting Toxicities (DLTs) is defined as at least possibly related to CAR.B7-H3T cell product administration.

  Up to 4 weeks

• Toxicity: Cytokine Release Syndrome (CRS)

  CRS will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild: Fever ≥38\^ o C, No hypotension, No hypoxia, Grade 2 - Moderate: Fever ≥38\^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe: Fever ≥ 38\^ o C, Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (\>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening: Fever ≥38\^oC, Hypotension requiring multiple vasopressors (excluding vasopressin), Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation, mechanical ventilation), Grade 5 - Death

  Up to 4 weeks

• Toxicity: Immune effector cell-associated neurotoxicity syndrome (ICANS)

  Neurotoxicity will be graded according to the Immune effector cell-associated neurotoxicity syndrome (ICANS) criteria between Grades 1-5. immune Effector Cell-Associated Encephalopathy (ICE) Score is a neurological assessment score that quantifies the severity of neurologic impairment. Each item in the assessment is associated with the point value indicated. The higher ICE scores are the better = lower the ICAN grade. An ICE score of 10 indicates a normal neurological assessment while an ICE score of 0-2 ICE Score indicates a severe neurological impairment.

  Up to 4 weeks

Secondary Outcomes (4)

• The recommended phase 2 dose (RP2D)

  Up to 4 weeks

• Progression Free Survival (PFS)

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years

• The disease control rate (DCR)

  Up to 6 months

Study Arms (1)

Chimeric Antigen Receptors

EXPERIMENTAL

blood will be collected to prepare the iC9-CAR.B7-H3 T cells. Disease-fighting T cells will be isolated and modified to prepare the iC9-CAR.B7-H3 T cells. In part 2, the iC9-CAR.B7-H3 T cells are given by infusion after completion of lymphodepletion chemotherapy.

Biological: iC9-CAR.B7-H3 T cells; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Cyclophosphamide DRUG

cyclophosphamide 300 mg/m2 IV will be given.

Also known as: Cycloblastin, Endoxan, Neosar, Procytox, Revimmune

Chimeric Antigen Receptors

Fludarabine DRUG

fludarabine 30 mg/m2 IV will be given.

Also known as: Fludara, Fludarabine Phosphate

Chimeric Antigen Receptors

iC9-CAR.B7-H3 T cells BIOLOGICAL

iC9-CAR.B7-H3 T cells will then be administered intraperitoneally

Also known as: iC9-CAR.B7-H3 T

Chimeric Antigen Receptors

Eligibility Criteria

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

You may qualify if:

• Unless otherwise noted, subjects must meet all of the following criteria to participate in all phases of the study:
• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information explained to, understood by and signed by the subject.
• Age ≥ 18 years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) of 0-2.
• The subject must have histologically or cytologically confirmed epithelial ovarian, peritoneal or fallopian tube cancer and must have a histological diagnosis of a high-grade serous histology based on local histopathological findings.
• Subject must have recurrent platinum-resistant or platinum-refractory disease defined as: A disease that has progressed by imagining while receiving platinum OR Disease that has recurred within 6 months of the last receipt of platinum-based chemotherapy. Rising CA-125 only is not considered as platinum-resistant or refractory disease.
• Having received at least 2 prior regimens (including front-line therapy).

You may not qualify if:

• 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 are eligible for this trial.
• The subject is not willing and not able to comply with study procedures based on the judgment of the investigator or protocol designee.
• \. The subject is not willing to undergo a biopsy prior to treatment, after infusion, and at the time of disease progression ), and the tumor is determined to be safe by the treating investigator for biopsy collection.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead

Study Sites (1)

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Recurrence

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Linda Van Le, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Catherine Cheng

CONTACT

919-445-4208; UNCImmunotherapy@med.unc.edu

Caroline Babinec

CONTACT

UNCImmunotherapy@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2024
• First Posted: March 12, 2024
• Study Start: July 29, 2024
• Primary Completion (Estimated): April 1, 2036
• Study Completion (Estimated): April 1, 2036
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)