Clinical Trial of Autologous B7-H3 CAR T Cells in Reoccurent Platinum-resistant Ovarian Tumors

NCT06646627 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: IRB-75080NCI-2025-00266
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single site, open label, Phase 1 study using a 3 + 3 dose escalation design in two cohorts of adults with recurrent, platinum-resistant ovarian tumors.

Conditions

Ovarian Cancer

Keywords

B7-H3CART

Outcome Measures

Primary Outcomes (2)

• Feasibility of B7-H3CART Manufacturing

  Feasibility is defined by the frequency of successful manufacturing runs of B7-H3CART that meet the established Investigational New Drug (IND) release criteria and the targeted dose level.

  2 years

• Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)

  MTD and/or RP2D defined in each arm (IP and IV) based on the number of events meeting definition of dose limiting toxicity (DLT) measured 28 days after infusion, tested in at least 6 evaluable participants in each arm.

  28 days after B7-H3CART infusion

Secondary Outcomes (1)

• Number of Subjects Meeting RECIST Radiographic Response at Day 28 to Determine Response Rate (RR) and Duration of Response (DOR)

  12 months

Study Arms (2)

Intraperitoneal (IP) Administration

EXPERIMENTAL

At the time of enrollment, based on imaging studies, clinical history and physical exams, the principal investigator will make a preliminary decision regarding Arm Assignment. Participants with ovarian cancer confined to the peritoneum will undergo laparoscopic placement of an intraperitoneal catheter (PowerPort™ device and catheter) for cell infusion. When feasible, a Tenckhoff catheter for research sample collection of ascites, will also be placed. If laparoscopic placement is not possible, the PowerPort catheter may be inserted in interventional radiology. If adhesions within the peritoneum would preclude effective distribution of CAR cells throughout the peritoneum, the participant may be placed in Arm B.

Drug: B7-H3CART

Intravenous (IV) Administration

EXPERIMENTAL

At the time of enrollment, based on imaging studies, clinical history and physical exams, the principal investigator will make a preliminary decision regarding Arm Assignment. Arm B will consist of participants with disease outside the peritoneum and with participants who either cannot undergo IP catheter insertion or who, in the judgement of the principal investigator do not have an intraperitoneal environment that would allow for adequate product distribution. Participants in Arm B will have a Tenckhoff catheter inserted in Interventional Radiology at least 7 days before the start of conditioning lymphodepletion.

Drug: B7-H3CART

Interventions

B7-H3CART DRUG

Dose Levels: Dose Level -1 Dose Level 1 Dose Level 2 Dose Level 3 Arm A IP(± 20%) (flat dose) Dose Level -1: 1 x 107 B7-H3CART Dose Level 1: 5 x 107 B7-H3CART Dose Level 2: 15 x 107 B7-H3CART Dose Level 3: 5 x 108 B7-H3CART Arm B: IV (± 20%) (weight based) Dose Level -1: 3 x 105 transduced cells/kg Dose Level 1: 1 x 106 transduced cells/kg Dose Level 2: 3 x 106 transduced cells/kg Dose Level 3: 10 x 106 transduced cells/kg

Intraperitoneal (IP) Administration; Intravenous (IV) Administration

Eligibility Criteria

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

You may qualify if:

• Disease: Histologically or cytologically confirmed diagnosis of ovarian cancer including serous, endometrioid, clear cell, mucinous, mixed epithelial, or undifferentiated. The study does not include pure sarcoma, stromal, or germ-cell tumors. Tumors that are substantially high-grade carcinoma and have focal elements of lower grade tumors or sarcomatous elements (e.g., carcinosarcoma) are eligible.
• Have measurable disease. Measurable disease is defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded). Each lesion must be ≥10 mm when measured by CT, MRI, or caliper measurement at clinical examination or ≥20 mm when measured by chest x-ray. Lymph nodes must be ≥15 mm in short axis when measured by CT or MRI.
• B7-H3 positive expression on malignant cells is NOT required but archival tissue must be available, or the subject must be willing to undergo tissue biopsy for expression analysis.
• Age: ≥ 18 years of age
• Prior Therapies: Subjects must have had at least 1 prior platinum-based chemotherapeutic regimen for the management of ovarian carcinoma.
• Patients should be considered platinum- refractory (progression while on a prior platinum chemotherapy) or resistant (persistence or recurrence within 6 months after a prior platinum-based chemotherapy) after all available curative standard therapies. There is no limit to the number of prior therapies.
• At least 3 weeks post chemotherapy or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy, except for systemic inhibitory/stimulatory immune checkpoint therapy that requires 3 months.
• Must have recovered from prior therapy toxicities to grade 1 or baseline, except for peripheral neuropathies, alopecia, etc.
• Performance Status: ECOG status of 2 or better (or Karnofsky Performance Status score of ≥60%) (See Section 11.1)
• Life expectancy at least 3 months, in the investigator's clinical judgement.
• Adequate bone marrow and major organ function.
• Hgb ≥ 10 g/dL
• ANC ≥ 1500/uL
• Platelet count ≥ 100,000/uL
• Absolute lymphocyte count ≥150/uL

You may not qualify if:

• \. Active infection or uncontrollable infection requiring systemic treatment within 1 week before screening. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
• \. Requirement for systemic corticosteroid therapy at doses higher than physiologic maintenance dosing (must be \< 5 mg/day of prednisone (or equivalent doses of other corticosteroids). Topical, inhaled or ocular steroids are allowed.
• \. Presence of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess.
• \. Malignant tumors other than the target tumor within 2 years prior to screening, except for the following: malignant tumors that have received radical treatment and no known active disease within ≥ 2 years prior to enrollment; or adequately treated non-melanoma skin cancers with no evidence of disease.
• \. Have any of the following heart conditions:
• New York Heart Association (NYHA) stage III or IV congestive heart failure;
• Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment;
• Clinically significant ventricular arrhythmia, or a history of unexplained syncope (except those caused by vasovagal or dehydration);
• History of severe nonischemic cardiomyopathy. 6. Known to have active or uncontrolled autoimmune diseases, such as Crohns disease, rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, etc.
• \. Ongoing HIV, HBV, or HCV infection. History of HBV or HCV is permitted if viral load is undetectable by qPCR and/or nucleic acid testing.
• \. Known or suspected untreated brain metastases. Patients with radiographically stable, asymptomatic previously irradiated lesions are eligible provided patient is \>4 weeks beyond completion of cranial irradiation and \>3 weeks off of corticosteroid therapy at the time of study intervention.
• \. Known sensitivities to any of the agents used in this study or their reagents including steroids, tocilizumab, DSMO, cyclophosphamide, fludarabine, etc.
• \. Prior history of clinically significant seizure disorder (e.g., not including childhood febrile seizures).
• \. Any other issue which, in the opinion of the treating physician or principal investigator, would make the patient ineligible for the study.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Palo Alto, California, 94304, United States

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms

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

Study Officials

• Oliver Dorigo, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bela Shah

CONTACT

650-723-0594; belashah@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 17, 2024
• Study Start: November 11, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: February 9, 2026

Record last verified: 2026-02

Locations

US (1)