Clinical trial NCT04562298: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Epithelial Ovarian Cancer
Keywords: Epithelial Ovarian Cancer
Lead sponsor: Shanghai East Hospital
Sponsor class: OTHER
Collaborators: name: Nanjing Legend Biotech Co.
name: East Clinical Center of Oncology
name: Anhui Provincial Hospital
First posted: 2020-09-24
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs)
timeFrame: 90 days post infusion
measure: MTD/ RP2D regimen finding
timeFrame: 90 days post infusion
measure: Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration
timeFrame: 2 years post infusion
Secondary outcomes:
measure: Disease control rate (DCR) after administration
timeFrame: 2 years post infusion
measure: Objective Response Rate (ORR) after administration
timeFrame: 2 years post infusion
measure: Time to Response (TTR) after administration
timeFrame: 2 years post infusion
measure: Duration of Response (DOR) after administration
timeFrame: 2 years post infusion
measure: Progress Free Survival (PFS) after administration
timeFrame: 2 years post infusion
measure: Overall Survival (OS) after administration
timeFrame: 2 years post infusion
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
Study officials:
affiliation: East Clinical Center of Oncology
name: Ye Guo, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Obstetrics & Gynecology Hospital of Fudan University
name: Yu Kang, PhD
role: PRINCIPAL_INVESTIGATOR
References: