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Epithelial Ovarian CancerPhase 1NCT04670068

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

A Phase 1 study testing CAR.B7-H3, Fludarabine and Cyclophosphamide in people with Epithelial Ovarian Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Epithelial Ovarian Cancer
What is being tested?
CAR.B7-H3, Fludarabine and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
27 Jan 2021to Feb 2030
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.
  • 8. 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).
  • 9. 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.
  • 10. Subject is willing and able to comply with study procedures based on the judgment of the investigator or protocol designee.
  • 11. Subject is willing to undergo a biopsy prior to treatment, at the time of final infusion, intraperitoneal catheter removal, and at the time of disease progression, and the tumor site is determined to be safe by the treating investigator for biopsy collection.
  • Eligibility Criteria Prior to Cell Procurement
  • Written informed consent to undergo cell procurement is explained to, understood by, and signed by the subject; the subject is given a copy of the informed consent form for cell procurement.
  • Subject has a life expectancy of≥ 3 months.
  • Subject has evidence of adequate organ function as defined by:
  • Total bilirubin ≤ 1.5 × ULN, unless attributed to Gilbert's Syndrome
  • AST / ALT ≤ 3 × ULN (Note: if intrahepatic liver metastases are present, AST and ALT must be ≤ 5 × ULN)
  • Creatinine ≤ 2 × ULN
  • Left ventricular ejection fraction (LVEF) • 40%, as measured by ECHO, with no additional evidence of decompensated heart failure.
  • Imaging results from within 90 days prior to procurement to assess the presence of active disease.
  • Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to cell procurement. Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided.

Who cannot join

  • 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 intraparenchymal lung metastases (note that pleural effusions are not exclusionary and that subjects with intraparenchymal liver disease and subjects with the retroperitoneal disease are allowed on the study).
  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

Other trials in United States

About this study

Official title: A Phase 1 Study of Autologous Activated T-cells Targeting the B7-H3 Antigen in Subjects With Recurrent Epithelial Ovarian Cancer

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.

Read the detailed description

This study is intended for the patients who have been diagnosed with Epithelial Ovarian Cancer that either came back or did not improve after previous treatments. 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 B7-H3 antigen (CAR.B7-H3 T cells) in patients with ovarian cancer. This treatment has not been approved by the Food and Drug Administration.

The study investigator's goal is to calculate the Maximum tolerated dose of the CAR.B7-H3 cells There are two parts to this study. In part 1, subject's blood sample will be used to manufacture the CAR.B7-H3 T cells.

Ovarian cancer cells carry a substance called B7-H3 which is not found in other healthy cells. the subject's T cells will be modified to make CAR.B7-H3 T cells so they may attack and destroy ovarian cancer cells that carry the B7-H3 substance. The CAR.B7-H3 T cells are given through a catheter in the abdomen, after completing three rounds of lymphodepletion chemotherapy. Lymphodepletion chemotherapy prepares the body to receive the CAR.B7-H3 T cells.

In part 2 of the study, the subjects will receive the CAR.B7-H3 T cells. Eligible patients will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for three consecutive days. If they continue to meet the eligibility criteria, the modified CAR.B7-H3 T cells will be given to them 2-14 days after the last lymphodepletion chemotherapy session. Three infusions of the CAR.B7-H3 T cells may be given to the subject through a catheter in the abdomen. Infusions will be done once a week.

Lymphodepletion chemotherapy and infusion of the CAR.B7-H3 T cells will happen at UNC Cancer Hospital. On the days the subjects receive the CAR.B7-H3 T cells infusion- Blood, fluid, and tumor samples will be collected from the subject for research purposes. Tumor biopsies are a mandatory part of this research.

Post infusion visits are - 3, 4, and 6 weeks. Additional visits will happen every 3 months for one year after the last infusion. Similar follow-up clinic visits will be completed annually, for a total of 5 years.

This is a research study to obtain new information that may help people in the future.

Being tested
CAR.B7-H3, Fludarabine, Cyclophosphamide
Keywords
Ovarian Cancer
Medical subject headings
Carcinoma, Ovarian Epithelial, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CAR.B7-H3Drug

    Also called Chimeric antigen receptor T cells with B7.H3 molecular target

    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.

  • FludarabineDrug

    Also called FLUDARA

    30 mg/m^2 IV for 3 consecutive days

  • CyclophosphamideDrug

    Also called Cytoxan

    300 mg/m^2 IV for 3 consecutive days

Study groups in NCT04670068
Study groupRoleWhat they receive
CAR.B7-H3 T cell productExperimentalUp 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.
Receives: Drug: CAR.B7-H3; Drug: Fludarabine; Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

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

  2. 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.

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

  3. 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.

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

Secondary outcomes (3)

  1. Disease Control Rate (DCR)

    Disease control rate will be defined as the percentage of subjects with complete response (CR), partial response (PR), and/or stable disease at 6 months per RECIST 1.1 criteria.

    Radiographic response will be measured by RECIST (Response Evaluation Criteria In Solid Tumors) Criteria, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Measured: 6 months after initial CAR-T cell infusion

  2. Progression Free Survival (PFS)

    Progression free survival (PFS) will be measured from the time of lymphodepletion prior to infusion with CAR.B7-H3 to progression (as defined per RECIST 1.1) or death.

    Radiographic response will be measured by RECIST, Response Evaluation Criteria In Solid Tumors Criteria, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

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

  3. Overall Survival (OS)

    Overall survival (OS) will be measured from the date of lymphodepletion prior to CAR.B7-H3 T cell product administration to the date of death.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Dec 2020
  2. Study start27 Jan 2021
  3. Primary completion19 Dec 2024
  4. Study completionFeb 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04670068
Sponsor's protocol ID
LCCC1818-ATL
Other IDs
R01CA256898
Status last verified
Dec 2025
First submitted
9 Dec 2020
Last updated
22 Dec 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 35468680

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CAR.B7-H3, Fludarabine and Cyclophosphamide in people with Epithelial Ovarian Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 22 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicities (DLTs) Based on National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) (time frame: Up to 10 weeks (Up 4 weeks after the last CAR-T cell infusion)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04670068, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2025.

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