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

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.

Study Overview

• Status: Terminated
• Conditions: Epithelial Ovarian Cancer
• Intervention / Treatment: Biological: LCAR-M23 cells

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai East Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. 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)
2. Age: 18-70 years (including 18 and 70 years)
3. Female subjects with histologically or cytologically confirmed advanced epithelial ovarian cancer including fallopian tube and primary peritoneal cancers
4. Mesothelin (MSLN) positive
5. Prior adequate standard of care, treatment failure or intolerance.
6. Imaging shows an evaluable tumor lesion
7. ECOG 0-1
8. Expected survival ≥ 3 months

Exclusion Criteria:

1. 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.)
2. Previously treated with CAR-T/TCR-T cell therapy against any target or other cell therapies or therapeutic tumor vaccine
3. Previously treated with any MSLN-targeted therapy
4. Brain metastases with central nervous system symptoms
5. Pregnant or lactating women
6. Any condition in which, in the opinion of the investigator, the subject is ineligible for participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: LCAR-M23 Chimeric Antigen Receptor T cell

Biological: LCAR-M23 cells; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR) after administration	Disease Control Rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease.	2 years post infusion
Objective Response Rate (ORR) after administration	Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after treatment via LCAR-M23 cell infusion, and the objective tumor response rate will be calculated for patients with measurable disease as per RECIST 1.1 criteria only.	2 years post infusion
Time to Response (TTR) after administration	Time to Response (TTR) is defined as the time interval from the date of first infusion of LCAR-M23 cell formulation to the date of the first response evaluation of the subject who has met all criteria for PR or better.	2 years post infusion
Duration of Response (DOR) after administration	Duration of Response (DOR) is defined as the time from the first documentation of response (PR or better) to the first documentation of disease progression evidence (as per RECIST 1.1 criteria) of the responders (who achieve PR or better response).	2 years post infusion
Progress Free Survival (PFS) after administration	Progression Free Survival (PFS) is defined as the time interval from the date of first infusion of LCAR-M23 cell formulation to the first documentation of disease progression (as per RECIST 1.1 criteria) or death (due to any cause), whichever occurs first.	2 years post infusion
Overall Survival (OS) after administration	Overall survival (OS) is defined as the time interval from the date of first infusion of LCAR-M23 cell formulation to death of the subject.	2 years post infusion

Collaborators and Investigators

• Sponsor: Shanghai East Hospital
• Collaborators: Anhui Provincial Hospital; Nanjing Legend Biotech Co.; East Clinical Center of Oncology
• Investigators: Principal Investigator: Ye Guo, PhD, East Clinical Center of Oncology; Principal Investigator: Yu Kang, PhD, Obstetrics & Gynecology Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2020
• Primary Completion (Actual): June 7, 2022
• Study Completion (Actual): June 7, 2022

Study Registration Dates

• First Submitted: September 19, 2020
• First Submitted That Met QC Criteria: September 19, 2020
• First Posted (Actual): September 24, 2020

Study Record Updates

• Last Update Posted (Actual): August 18, 2022
• Last Update Submitted That Met QC Criteria: August 15, 2022
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Epithelial Ovarian Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: BM2L201906

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No