Exploratory Study of Novel MSLN CAR-T Cell Therapy in Patients With MSLN-positive Advanced Refractory Solid Tumors

NCT05531708 | Withdrawn Phase 1

• 1 other identifier: 2021-IIT-004-E02
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label, exploratory clinical study to evaluate the safety and efficacy of novel Mesothelin CAR-T in patients with Mesothelin-positive advanced refractory solid tumors.

Conditions

Mesothelin-positive Advanced Refractory Solid Tumors

Keywords

Anti-mesothelin CAR-T; Solid tumor

Outcome Measures

Primary Outcomes (3)

• TEAEs

  Incidence and severity of treatment emergent adverse events.

  4 weeks after the CAR-T cells infusion

• TRAEs

  Incidence and severity of treatment related adverse events.

  4 weeks after the CAR-T cells infusion

• AESIs

  Incidence and severity of AEs of special interest.

  4 weeks after the CAR-T cells infusion

Secondary Outcomes (2)

• Objective Response Rate (ORR) (PR+CR)

  12 weeks

• Duration of Overall Response（DOR）

  24 months

Study Arms (1)

Anti-mesothelin CAR-T cells

EXPERIMENTAL

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, anti-mesothelin CAR-T cells.

Biological: Anti-mesothelin CAR-T cells; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

Anti-mesothelin CAR-T cells BIOLOGICAL

D0: Anti-mesothelin CAR-T cells are autologous genetically modified T cells. Cells will be infused intravenously.

Anti-mesothelin CAR-T cells

Fludarabine DRUG

D-7 to D-3: Fludarabine (25 mg/m\^2/day) will be administered intravenously for 5 days.

Also known as: Fludara

Anti-mesothelin CAR-T cells

Cyclophosphamide DRUG

D-7 and D-6: Cyclophosphamide (60 mg/kg/day) will be administered intravenously for 2 days.

Also known as: Cytoxan

Anti-mesothelin CAR-T cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Solid tumors positive for the Mesothelin antigen by Immunohistochemistry/Immunocytochemistry (IHC/ICC); histological diagnosis of malignancy refractory to, or relapsing after standard therapy.
• At least one measurable lesion according to RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥ 3 months.
• Neutrophils ≥ 1.0×10\^9/L; Lymphocytes ≥ 0.5×10\^9/L; Hemoglobin ≥ 80 g/L; Platelets ≥ 75×10\^9/L.
• Adequate hepatic, renal, cardiac and coagulation function defined as:
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN); patients with liver metastasis must be ≤ 5 × ULN;
• Total bilirubin (TBIL) ≤ 1.5 × ULN; TBIL of patients with Gilbert's Syndrome must less than 3.0 mg/dL;
• Serum creatinine (Cr) ≤ 1.5 × ULN, and creatinine clearance rate (Ccr) ≥ 60 mL/min;
• Left ventricular ejection fraction (LVEF) \> 45%;
• Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
• Negative screen for infectious disease markers including HIV-Ab, HCV-Ab, HBeAg, HBsAg, and syphilis. Note - Participants with history of prior HBV infection are eligible if the HBV viral load is undetectable. Participants with a history of HCV infection who were treated for hepatitis C and cured are eligible if hepatitis C viral load is undetectable.
• The toxicities from any prior therapy must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo) according to NCI CTCAE v5.0.
• The washout period of previous treatment:
• Cytotoxic chemicals, monoclonal antibodies or immunotherapy should be washed out for at least 4 weeks before leukapheresis; anti-CTLA-4 antibodies should be washed out for at least 6 weeks;

You may not qualify if:

• Patients with central nervous system involvement.
• Patients with clinically significant systemic disease (such as: severe active infection or significant cardiac, pulmonary, hepatic, nervous system, or other organ dysfunction) that evaluated by the investigator would impair the patient's ability to tolerate the treatments used in this study or significantly increase the risk of complications.
• Any known or suspected autoimmune disease; or active, chronic or recurrent immune-mediated disease (within one year prior to enrollment) requiring steroid or other immunosuppressive therapy.
• History of severe systemic hypersensitivity reaction to the drugs/ingredients used in this study.
• Have received any allogeneic tissue/organ transplantation (including bone marrow transplantation, stem cell transplantation, liver transplantation, kidney transplantation), except for the transplantation that does not require immunosuppressive therapy (such as: corneal transplantation, hair transplantation.)
• Have received any genetic engineering modified T cell therapy (including CAR-T, TCR-T).
• History of major surgery and unrecovered severe trauma within 4 weeks prior to signing informed consent.
• History of another malignancy tumor, except for non-melanoma skin cancer and carcinoma in situ of bladder, stomach, colon, cervix/dysplasia, melanoma, or breast.
• History of neuropsychiatric diseases diagnosed by the ICD-11 criteria or evaluated by investigator.
• For any other reasons, the patients are believed not suitable for participation in this study by investigators.

Sponsors & Collaborators

• Shanghai Pudong Hospital: lead
• UTC Therapeutics Inc.: collaborator

Study Sites (1)

Shanghai Pudong Hospital, Fudan University Affiliated Pudong Medical Center

Shanghai, Shanghai Municipality, 201399, China

Location

MeSH Terms

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Zhiguo Long

  Shanghai Pudong Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2022
• First Posted: September 8, 2022
• Study Start: April 2, 2021
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2026
• Last Updated: March 1, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)