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

Phase 1

Terminated

• Conditions: Epithelial Ovarian Cancer
• Interventions: Biological: LCAR-M23 cells

• Registration Number: NCT04562298
• Lead Sponsor: Shanghai East Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-19
• Study First Submitted QC: 2020-09-19
• Study First Posted: 2020-09-24
• Study Start: 2020-10-21
• Status Verified: 2021-10
• Primary Completion: 2022-06-07
• Study Completion: 2022-06-07
• Last Update Submitted: 2022-08-15
• Last Update Posted: 2022-08-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 15

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LCAR-M23 Chimeric Antigen Receptor T cell	LCAR-M23 cells	-

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs)	90 days post infusion	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.
Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration	2 years post infusion	Venous blood samples will be collected for measurement of CAR-T positive cellular concentration
MTD/ RP2D regimen finding	90 days post infusion	Maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D)

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) after administration	2 years post infusion	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.
Overall Survival (OS) after administration	2 years post infusion	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.
Progress Free Survival (PFS) after administration	2 years post infusion	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.
Time to Response (TTR) after administration	2 years post infusion	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.
Duration of Response (DOR) after administration	2 years post infusion	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).
Disease control rate (DCR) after administration	2 years post infusion	Disease Control Rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease.

Trial Locations

Locations (1)

Shanghai East Hospital; 🇨🇳 Shanghai, Shanghai, China