Phase I Study of Autologous CAR T-Cells Targeting the B7-H3 Antigen in Recurrent Epithelial Ovarian

NCT04670068 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 2 other identifiers: LCCC1818-ATLR01CA256898
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is single center, open-label phase 1 dose escalation trial that uses modified 3+3 design to identify a recommended phase 2 dose (RP2D) of CAR.B7-H3 T cell product. An expansion cohort will enroll additional subjects at the RP2D for a total enrollment of up to 21 subjects on the protocol.

Conditions

Epithelial Ovarian Cancer

Keywords

Ovarian Cancer

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose Limiting Toxicities (DLTs) Based on National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE)

  Dose-limiting toxicity (DLT) assessments will include toxicities that are at least possibly related to the CAR.B7-H3 T cell product and that occur from the day of the initial infusion through four weeks after the final administration. DLTs are defined as toxicities of Grade ≥3. All toxicities will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, which rates severity from Grade 1 (mild) to Grade 5 (death).

  Up to 10 weeks (Up 4 weeks after the last CAR-T cell infusion)

• Number of Participants With Dose Limiting Toxicities (DLTs) Based on Cytokine Release Syndrome (CRS)

  Dose-limiting toxicities (DLTs) will include any toxicity that is at least possibly related to the CAR.B7-H3 T cell product and occurs from the first infusion through 4 weeks after the final dose. DLTs are defined as Grade ≥3 cytokine release syndrome (CRS) that does not improve to Grade ≤2 within 7 days. CRS will be graded per protocol criteria on a Grade 1 (mild) to Grade 5 (death) scale.

  Up to 10 weeks (Up 4 weeks after the last CAR-T cell infusion)

• Number of Participants With Dose Limiting Toxicities (DLTs) Based on Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

  Dose-limiting toxicity (DLT) assessments will include any toxicity that is at least possibly related to the CAR.B7-H3 T cell product, occurring from the day of the first infusion through four weeks after the final cell product administration. DLTs are defined as Grade ≥3 Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) or any other Grade ≥3 non-hematologic toxicity, including allergic reactions to T cell infusions. ICANS will be graded using protocol-defined criteria on a scale from Grade 1 (mild) to Grade 4 (critical). Cytokine Release Syndrome (CRS), if observed, will be graded on a scale from Grade 1 (mild) to Grade 5 (death), per the criteria outlined in the protocol.

  Up to 10 weeks (Up 4 weeks after the last CAR-T cell infusion)

Secondary Outcomes (3)

• Disease Control Rate (DCR)

  6 months after initial CAR-T cell infusion

• Progression Free Survival (PFS)

  From the date of lymphodepletion to the date of progression or death up to 5 years

• Overall Survival (OS)

  From the date of lymphodepletion to the date of death up to 5 years

Study Arms (1)

CAR.B7-H3 T cell product

EXPERIMENTAL

Up to 12 patients will receive three weekly CAR.B7-H3 T cell product infusions at the same dose. To determine the recommended phase 2 dose (RP2D), a modified 3+3 dose escalation design will be used to evaluate two dose levels: Dose Level 1 (7.5x10\^7 cells/infusion), Dose Level 2 (2x10\^8 cells/infusion). If this dose is not tolerated, then a lower dose of 3.75 × 10\^6 cells/infusion will be explored. Up to 3 dose levels of CAR.B7-H3 cells will be tested with at least 3 patients enrolled at each dose cohort before dose escalation is considered based on the incidence of dose limiting toxicity (DLT). An expansion cohort will enroll up to 9 patients at the recommended phase 2 dose. Prior to receiving the infusions, patients will undergo lymphodepletion with fludarabine and cyclophosphamide.

Drug: CAR.B7-H3; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

CAR.B7-H3 DRUG

Two dose levels will be evaluated: Dose Level 1 (7.5x10\^7 cells/infusion), dose Level 2 (2x10\^8 cells/infusion). If dose limiting toxicities (DLTs) are observed per protocol, Dose Level -1 (3.75x10\^6 cells/infusion) will be evaluated.

Also known as: Chimeric antigen receptor T cells with B7.H3 molecular target

CAR.B7-H3 T cell product

Fludarabine DRUG

30 mg/m\^2 IV for 3 consecutive days

Also known as: FLUDARA

CAR.B7-H3 T cell product

Cyclophosphamide DRUG

300 mg/m\^2 IV for 3 consecutive days

Also known as: Cytoxan

CAR.B7-H3 T cell product

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information explained to, understood by, and signed by the subject or their legally authorized representative; subject was given a copy of the informed consent form.
• Older than 18 years at the time of consent.
• Subject has adequate performance status as defined by ECOG score of ≤ 2.
• Subjects must have histologically or cytologically confirmed epithelial ovarian, peritoneal or fallopian tube cancer and must have a histological diagnosis of high-grade serous histology based on local histopathological findings.
• Subjects must have recurrent platinum-resistant or platinum-refractory disease defined as:
• Disease that has progressed by imaging 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 a platinum-resistant or refractory disease.
• Having received at least 2 prior regimens.
• Have failed prior therapy with a PARP inhibitor if the subject has a germline or somatic BRCA mutation.
• Subjects must have an evaluable disease - defined as:
• Measurable disease per RECIST 1.1 OR
• Non-measurable disease (defined as solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions) OR
• Ascites and/or pleural effusion that has been pathologically demonstrated to be disease-related in the setting of a CA-125 \> 2 × ULN.
• \. Subjects must be able to have an intraperitoneal port placed either by vascular interventional radiology or surgically in the operating room. (Note: The intraperitoneal port will not be placed until the subject is determined to be otherwise eligible to receive the CAR.B7-H3 infusion and until the subject is determined to be otherwise eligible to receive lymphodepletion).
• \. Female subjects of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of highly effective methods of contraception from the time of informed consent until 180 days 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.

You may not qualify if:

• Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated in the study).
• Subject is deemed unlikely to be a candidate for successful intraperitoneal catheter placement by radiographic assessment.
• Subject has brain metastases. A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to being screened for eligibility, have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic.
• Subject has current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowel obstruction within 3 months prior to starting treatment.
• Subject has a history of an intra-abdominal abscess within the past 3 months.
• Subject has a history of gastrointestinal perforation.
• The subject has a history of symptomatic diverticular disease, confirmed by CT or colonoscopy.
• Subject is dependent on intravenous hydration or total parenteral nutrition.
• Subject has a known additional malignancy that is active and/or progressive and requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
• Current 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.
• Subject has active infection with HIV, HTLV, HBV, and HCV (tests can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells). Note: To meet eligibility subjects are required to be negative for HIV antibody or HIV viral load, negative for HTLV1 and 2 antibodies or PCR negative for HTLV1 and 2, negative for Hepatitis B surface antigen, negative for HCV antibody or HCV viral load.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• Golubovskaya V. CAR-T Cells Targeting Immune Checkpoint Pathway Players. Front Biosci (Landmark Ed). 2022 Apr 2;27(4):121. doi: 10.31083/j.fbl2704121.

  PMID: 35468680 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial; Ovarian Neoplasms

Interventions

Immunotherapy, Adoptive; fludarabine; fludarabine phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; 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

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

This study was closed to accrual before reaching target accrual.

Results Point of Contact

• Title: Kelly Hoye, MS, CCRP Study coordinator - Clinical Immunotherapy Program
• Organization: UNC Lineberger Comprehensive Cancer Center

khoye@email.unc.edu

919-445-9676

Study Officials

• Linda Van Le, MD

  UNC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: December 9, 2020
• First Posted: December 17, 2020
• Study Start: January 27, 2021
• Primary Completion: December 19, 2024
• Study Completion (Estimated): February 1, 2030
• Last Updated: December 22, 2025
• Results First Posted: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)