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

NCT05211557 | Recruiting Phase 1

• 1 other identifier: XYFY2021-KL184-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Ovarian Cancer

Keywords

Fully Human B7H3 CAR-T; Recurrent Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity of fully human B7H3 CAR-T cells

  Dose limiting toxicity (DLT), including the type, frequency, severity and duration of adverse events, such as cytokine release syndrome (CRS), on-target off-tumor, immune effector cell-associated neurotoxicity syndrome, will be monitored and assessed.

  1 month

• Objective response of fully human B7H3 CAR-T cells

  Objective response rate (ORR) including complete response (CR), partial response (PR), and/or stable disease, will be determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. 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. Progressive Disease (PD): 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.

  1 month

Secondary Outcomes (1)

• In vivo persistence of fully human B7H3 CAR-T cells

  1 month

Other Outcomes (2)

• Progress free survival (PFS)

  up to 5 years

• Overall survival (OS)

  up to 5 years

Study Arms (1)

fhB7H3.CAR-T cells

EXPERIMENTAL

In phase I study, 9 enrolled patients diagnosed with advanced ovarian cancer will receive one-time infusion of fhB7H3.CAR-Ts at the doses of 1×10\^6/kg, 3×10\^6/kg and 5×10\^6/kg, 3 patients for each dose. To further confirm the therapeutic efficacy, in phase II study, 6 enrolled patients will receive an optimal dose (balancing effectiveness and toxicity) of fhB7H3.CAR-Ts. Prior to receiving the infusions, patients will undergo lymphodepletion with fludarabine and cyclophosphamide.

Biological: fhB7H3.CAR-Ts

Interventions

fhB7H3.CAR-Ts BIOLOGICAL

Three dose levels will be evaluated: Dose Level 1 (1×10\^6/kg), dose Level 2 (3×10\^6/kg) and dose Level 3 (5×10\^6/kg). If dose limiting toxicities (DLTs) are observed in each doses, Dose Level -1 (0.5×10\^6/kg /infusion) will be evaluated. Other Name: B7H3 targeting chimeric antigen receptor T cells Drug: Fludarabine 30 mg/m2 i.v. for 3 consecutive days (Day -5\~Day -3) Other Name: FLUDARA Drug: Cyclophosphamide 750 mg/m2 i.v. for once (Day -5) Other Name: Cytoxan

fhB7H3.CAR-T cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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\< 1.5 × 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.

You may not qualify if:

• 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. -

Sponsors & Collaborators

• The Affiliated Hospital of Xuzhou Medical University: lead
• Xuzhou Medical University: collaborator
• IIT MediTech (Jiangsu) Co. Ltd: collaborator

Study Sites (1)

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221002, China

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

• Junnian Zheng, M.D., Ph.D.

  The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University

  STUDY DIRECTOR

• Longzhen Zhang, M.D., Ph.D.

  The Affiliated Hospital of Xuzhou Medical University

  PRINCIPAL INVESTIGATOR

• Gang Wang, Ph.D.

  Xuzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liantao Li, M.D., Ph.D.

CONTACT

+86-516-85582530; liliantao@xzhmu.edu.cn

Xin Ding, M.D., Ph.D.

CONTACT

+86-516-83355832; dingxin81@163.com

Study Design

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

Study Record Dates

• First Submitted: January 13, 2022
• First Posted: January 27, 2022
• Study Start: November 16, 2021
• Primary Completion: August 31, 2023
• Study Completion (Estimated): August 31, 2026
• Last Updated: January 27, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)