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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Epithelial Ovarian Cancer

Intervention / Treatment
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* Biological: LCAR-M23 cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCAR-M23 Chimeric Antigen Receptor T cell<br> | Biological: LCAR-M23 cells<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epithelial Ovarian Cancer