Study of Fully Human B7H3 CAR-T in Treating Recurrent Malignant Ovarian Cancer

  • STATUS
    Recruiting
  • End date
    Aug 31, 2026
  • participants needed
    15
  • sponsor
    The Affiliated Hospital of Xuzhou Medical University
Updated on 25 March 2022
platelet count
measurable disease
neutrophil count
cancer antigen 125
cancer of the ovary

Summary

This is single center, open-label phase I, non-randomized study which will enroll patients with recurrent advanced ovarian cancer to evaluate the safety, feasibility, and efficacy of fully human B7H3 CAR-T cells (fhB7H3.CAR-Ts) via using a '3+3+3' dose escalation design. In the dose expansion cohort, six patients will be enrolled to further assess their efficacy with the optimal dosage.

Description

The purpose of this study is to test the safety and efficacy of a newly developed fully human scFv-armed B7H3 targeting chimeric antigen receptor T cells (fhB7H3.CAR-Ts), which are supposed to attack and eliminate B7H3-positive cancer cells. The patients who have been diagnosed as recurrent or relapsed malignant ovarian cancer, especially ovarian cancer patients with refractory ascites, will be potentially enrolled after assessing the expression of B7H3 antigen in tumor tissue by immunohistochemistry staining or ascitic tumor cells by flow cytometry.

After enrollment, participants' peripheral blood mononuclear cells will be collected and used to manufacture fhB7H3.CAR-Ts. Before infusion, the patients will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for three consecutive days. Two days later after lymphodepletion, the fhB7H3.CAR-Ts would be given through an abdominal catheter for intraperitoneal infusion. From the day of infusion, participants' peripheral blood and ascites will be collected twice a week in the first month for monitoring the survival of fhB7H3.CAR-Ts and evaluating the therapeutic efficacy. Additional follow-up and examination will be performed monthly for the first three month and then trimonthly until one year. Thereafter, annual follow-up will be completed for 5 years.

In addition, since the fhB7H3.CAR-Ts containing a RQR8 safety-switch which could be targeted and removed by Rituximab. Participants who experience life-threatening toxicities caused by uncontrollable proliferation of fhB7H3.CAR-Ts will receive infusion of Rituximab (Rituxan or Ruxience or Halpryza) to assess the ability of RQR8 safety-switch to eliminate infused fhB7H3.CAR-Ts.

This is an investigator-initiated clinical study to assess first-line clinical performance of novel fhB7H3.CAR-Ts which may help other advanced and recurrent ovarian cancer patients in the future.

Details
Condition Ovarian Cancer
Treatment fhB7H3.CAR-Ts
Clinical Study IdentifierNCT05211557
SponsorThe Affiliated Hospital of Xuzhou Medical University
Last Modified on25 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Procurement and T-cell production eligibility: a previously evaluation confirmed autologous peripheral blood mononuclear cells can be used for T-cell production
Written informed consent and authorization for release of personal health information
Subject has adequate performance status as defined by ECOG score of ≤ 2
Expected life expectancy is no less than 12 weeks
Subjects must have histologically or cytologically confirmed ovarian cancer. And cancer tissue or ascitic cancer cells are measured positive for B7H3 expression
Subjects must have recurrent or refractory disease after or during first-line treatment
Defined as
Radiographic progression or Continuous Elevation of CA125
Subjects must have evaluable disease - defined as
Measurable disease with tumor length ≥ 10mm or enlarged lymph nodes ≥ 15mm
according to RECIST v1.1 criteria
Adequate organ function - defined as
Blood routine
white blood cell count ≥ 3 × 10^9 / L; neutrophil count ≥ 1.5 × 10^9 / L
hemoglobin ≥ 9g/dL; platelet count ≥ 80 × 10^9 / L; INR< 1.5 × ULN; PT, APTT<
5 × ULN
The liver, kidney, lung and cardiopulmonary function
Urea and serum creatinine ≤ 1.5 × ULN; Left ventricular ejection fraction ≥ 40%
Baseline oxygen saturation ≥ 95%; Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN
Not pregnant with negative serum pregnancy test within 3 days prior to enrollment
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 8 weeks after study treatment discontinuation

Exclusion Criteria

Subject has primary immunodeficiency syndrome or history of severe allergic reaction
Subject has active infection with HIV, HTLV, HBV, HCV
Subject has severe, uncontrolled intercurrent bacterial, viral or fungal infection
Subject has a history of gastrointestinal perforation, clinical and/or radiographic
evidence of bowel obstruction, or intra-abdominal abscess within 3 months prior to
starting treatment
Subject has active malignancy under treatment other than ovarian cancer
Subject has Grade ≥ 3 cardiac dysfunction or symptomatic arrhythmia requiring
intervention
Subject is current using of systemic corticosteroids at doses ≥10 mg prednisone daily
or its equivalent
Subject has not recovered from toxicity of previous anti-tumor treatment (CTCAE 5.0)
Subject is pregnant or breastfeeding
Unwilling or unable to provide consent/assent for participation in the study. -
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