A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LCAR-M23, a CAR-T Cell Therapy Targeting MSLN in Patients With Relapsed and Refractory Epithelial Ovarian Cancer

NCT04562298 | Terminated Phase 1

• 1 other identifier: BM2L201906
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, single-arm, open-label, single-dose dose finding and extension study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy profiles of the LCAR-M23 CAR-T cell therapy in subjects with relapsed and refractory epithelial ovarian cancer after prior adequate standard of care.

Conditions

Epithelial Ovarian Cancer

Keywords

Epithelial Ovarian Cancer

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs)

  Dose-limiting toxicity (DLT) refers to a drug-related toxicity during treatment with the drug, the severity of which is clinically unacceptable, limiting the further escalation of drug dose. An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment.

  90 days post infusion

• MTD/ RP2D regimen finding

  Maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D)

  90 days post infusion

• Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration

  Venous blood samples will be collected for measurement of CAR-T positive cellular concentration

  2 years post infusion

Secondary Outcomes (6)

• Disease control rate (DCR) after administration

  2 years post infusion

• Objective Response Rate (ORR) after administration

  2 years post infusion

• Time to Response (TTR) after administration

  2 years post infusion

• Duration of Response (DOR) after administration

  2 years post infusion

• Progress Free Survival (PFS) after administration

  2 years post infusion

Study Arms (1)

LCAR-M23 Chimeric Antigen Receptor T cell

EXPERIMENTAL

Biological: LCAR-M23 cells

Interventions

LCAR-M23 cells BIOLOGICAL

Prior to infusion of LCAR-M23, subjects will receive a premedication regimen (intravenous infusion of cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 once daily for 3 days; fludarabine dose reduction to 25 mg/m2 and cyclophosphamide to 250 mg/m2 are allowed if the subject' s creatinine clearance is 50-70 mL/min/1.73 m2). A single dose, single Infusion of LCAR-M23 is scheduled 5 to 7 days after the initiation of the premedication regimen.

LCAR-M23 Chimeric Antigen Receptor T cell

Eligibility Criteria

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

You may qualify if:

• The subjects have been fully informed of the possible risks and benefits of participating in this study and have voluntarily signed the informed consent form (ICF)
• Age: 18-70 years (including 18 and 70 years)
• Female subjects with histologically or cytologically confirmed advanced epithelial ovarian cancer including fallopian tube and primary peritoneal cancers
• Mesothelin (MSLN) positive
• Prior adequate standard of care, treatment failure or intolerance.
• Imaging shows an evaluable tumor lesion
• ECOG 0-1
• Expected survival ≥ 3 months

You may not qualify if:

• Patients who have received the following anti-tumor treatments prior to apheresis:
• Cytotoxic therapy within 14 days
• Small molecule targeted therapy within 14 days or at least 5 half-lives, whichever is shorter
• Therapy with monoclonal antibody within 21 days
• Immunomodulatory therapy within 7 days
• Radiotherapy within 14 days and endocrine therapy within 14 days (including tamoxifen, aromatase inhibitor, high-potency progesterone and gonadotropin-releasing hormone analogue, etc.)
• Previously treated with CAR-T/TCR-T cell therapy against any target or other cell therapies or therapeutic tumor vaccine
• Previously treated with any MSLN-targeted therapy
• Brain metastases with central nervous system symptoms
• Pregnant or lactating women
• Any condition in which, in the opinion of the investigator, the subject is ineligible for participation in the study

Sponsors & Collaborators

• Shanghai East Hospital: lead
• Nanjing Legend Biotech Co.: collaborator
• East Clinical Center of Oncology: collaborator
• Anhui Provincial Hospital: collaborator

Study Sites (1)

Shanghai East Hospital

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian 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

Study Officials

• Ye Guo, PhD

  East Clinical Center of Oncology

  PRINCIPAL INVESTIGATOR

• Yu Kang, PhD

  Obstetrics & Gynecology Hospital of Fudan University

  PRINCIPAL INVESTIGATOR

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: September 19, 2020
• First Posted: September 24, 2020
• Study Start: October 21, 2020
• Primary Completion: June 7, 2022
• Study Completion: June 7, 2022
• Last Updated: August 18, 2022

Record last verified: 2021-10

Locations

CN (1)