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A Single-Center, 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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04562298
Recruitment Status : Not yet recruiting
First Posted : September 24, 2020
Last Update Posted : September 24, 2020
Sponsor:
Collaborators:
Nanjing Legend Biotech Co.
East Clinical Center of Oncology
Information provided by (Responsible Party):
Shanghai East Hospital

Brief Summary:
This study is a prospective, single-arm, single-center, 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.

Condition or disease Intervention/treatment Phase
Epithelial Ovarian Cancer Biological: LCAR-M23 cells Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-Center, 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
Estimated Study Start Date : September 30, 2020
Estimated Primary Completion Date : November 1, 2022
Estimated Study Completion Date : November 1, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer

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.




Primary Outcome Measures :
  1. Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs) [ Time Frame: 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.

  2. MTD/ RP2D regimen finding [ Time Frame: 90 days post infusion ]
    Maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D)

  3. Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration [ Time Frame: 2 years post infusion ]
    Venous blood samples will be collected for measurement of CAR-T positive cellular concentration


Secondary Outcome Measures :
  1. Disease control rate (DCR) after administration [ Time Frame: 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 per RECIST 1.1 only.

  2. Objective Response Rate (ORR) after administration [ Time Frame: 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.

  3. Time to Response (TTR) after administration [ Time Frame: 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.

  4. Duration of Response (DOR) after administration [ Time Frame: 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).

  5. Progress Free Survival (PFS) after administration [ Time Frame: 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.

  6. Overall Survival (OS) after administration [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 longer
    • Investigational drug therapy within 28 days (if the above-mentioned therapy is also an investigational drug therapy, a 28-day washout period should be followed)
    • Therapy with monoclonal antibody within 28 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04562298


Contacts
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Contact: Ye Guo, PhD +86 ext 13501678472 pattrickguo@gmail.com
Contact: Yu Kang, PhD +86 ext 13636328211 ykang@126.com

Locations
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China, Shanghai
Shanghai East Hospital
Shanghai, Shanghai, China
Contact: Ye Guo, PhD    +86 ext 13501678472    pattrickguo@gmail.com   
Principal Investigator: Ye Guo, PhD         
Sponsors and Collaborators
Shanghai East Hospital
Nanjing Legend Biotech Co.
East Clinical Center of Oncology
Investigators
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Principal Investigator: Ye Guo, PhD East Clinical Center of Oncology
Principal Investigator: Yu Kang, PhD Obstetrics & Gynecology Hospital of Fudan University
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Responsible Party: Shanghai East Hospital
ClinicalTrials.gov Identifier: NCT04562298    
Other Study ID Numbers: BM2L201906
First Posted: September 24, 2020    Key Record Dates
Last Update Posted: September 24, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shanghai East Hospital:
Epithelial Ovarian Cancer
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type