Back to resultsA 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
Primary Purpose
Epithelial Ovarian Cancer
Status
Terminated
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
LCAR-M23 cells
Sponsored by
About this trial
This is an interventional treatment trial for Epithelial Ovarian Cancer focused on measuring Epithelial Ovarian Cancer
Eligibility Criteria
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
Sites / Locations
- Shanghai East Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
LCAR-M23 Chimeric Antigen Receptor T cell
Arm Description
Outcomes
Primary Outcome Measures
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.
MTD/ RP2D regimen finding
Maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D)
Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration
Venous blood samples will be collected for measurement of CAR-T positive cellular concentration
Secondary Outcome Measures
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.
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.
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.
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).
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.
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.
Full Information
NCT ID
NCT04562298
First Posted
September 19, 2020
Last Updated
August 15, 2022
Sponsor
Shanghai East Hospital
Collaborators
Nanjing Legend Biotech Co., East Clinical Center of Oncology, Anhui Provincial Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04562298
Brief Title
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
Official Title
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 Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Terminated
Why Stopped
Both the sponsors and collaborator are considering terminating the study.
Study Start Date
October 21, 2020 (Actual)
Primary Completion Date
June 7, 2022 (Actual)
Study Completion Date
June 7, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai East Hospital
Collaborators
Nanjing Legend Biotech Co., East Clinical Center of Oncology, Anhui Provincial Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epithelial Ovarian Cancer
Keywords
Epithelial Ovarian Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LCAR-M23 Chimeric Antigen Receptor T cell
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
LCAR-M23 cells
Intervention Description
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.
Primary Outcome Measure Information:
Title
Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs)
Description
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.
Time Frame
90 days post infusion
Title
MTD/ RP2D regimen finding
Description
Maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D)
Time Frame
90 days post infusion
Title
Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration
Description
Venous blood samples will be collected for measurement of CAR-T positive cellular concentration
Time Frame
2 years post infusion
Secondary Outcome Measure Information:
Title
Disease control rate (DCR) after administration
Description
Disease Control Rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease.
Time Frame
2 years post infusion
Title
Objective Response Rate (ORR) after administration
Description
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.
Time Frame
2 years post infusion
Title
Time to Response (TTR) after administration
Description
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.
Time Frame
2 years post infusion
Title
Duration of Response (DOR) after administration
Description
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).
Time Frame
2 years post infusion
Title
Progress Free Survival (PFS) after administration
Description
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 Frame
2 years post infusion
Title
Overall Survival (OS) after administration
Description
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.
Time Frame
2 years post infusion
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ye Guo, PhD
Organizational Affiliation
East Clinical Center of Oncology
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Yu Kang, PhD
Organizational Affiliation
Obstetrics & Gynecology Hospital of Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai East Hospital
City
Shanghai
State/Province
Shanghai
Country
China
12. IPD Sharing Statement
Learn more about this trial
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
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