αPD1-MSLN-CAR T Cells for the Treatment of MSLN-positive Advanced Solid Tumors

NCT04503980 | Unknown Early Phase 1

• 1 other identifier: BZDS1901
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of autologous mesothelin (MSLN)-targeted chimeric antigen receptor (MSLN-CAR) T cells secreting PD-1 nanobodies (αPD1-MSLN-CAR T cells) in patients with solid tumors.

Conditions

Colorectal Cancer; Ovarian Cancer

Keywords

Solid tumors; CAR T cell

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity （DLT）

  Safety

  After 28 days of single infusion

Secondary Outcomes (6)

• Maximum tolerated dose (MTD)

  After 28 days of single infusion

• Objective response rate (ORR)

  Month 12

• Progression-free survival (PFS)

  Month 12

• Overall survival (OS)

  Month 12

• Peak Plasma Concentration (Cmax)

  Month 12

Study Arms (1)

CAR T cells therapy

EXPERIMENTAL

The safety and efficacy of αPD1-MSLN-CAR T cells will be assessed in a standard 3+3 dose escalation approach. Four doses of CAR T cells will be evaluated in this study: 1×10\^5 CAR+ T cells/kg, 3×10\^5 CAR+ T cells/kg, 1×10\^6 CAR+ T cells/kg, and 3×10\^6 CAR+ T cells/kg.

Biological: αPD1-MSLN-CAR T cells

Interventions

αPD1-MSLN-CAR T cells BIOLOGICAL

Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of αPD1-MSLN-CAR T cells. During αPD1-MSLN-CAR T cells production, subjects will receive cyclophosphamide for the purpose of lymphocytes depletion. After lymphodepletion, subjects will receive one dose treatment with αPD1-MSLN-CAR T cells by intravenous (IV) injection. The initial dose of 1×10\^5 CAR+ T cells/kg will be infused on day 0.

CAR T cells therapy

Eligibility Criteria

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

You may qualify if:

• Patients must have a histological or cytological diagnosis of advanced solid tumors, such as ovarian cancer，Cholangiocarcinoma，colorectal cancer;
• Patients must have failed established standard medical anti-cancer therapies；
• Greater than or equal to 18 years of age and less than or equal to 70 years of age on day of signing informed consent；
• Life expectancy \>3 months；
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Subjects must meet blood coagulation parameters and have adequate venous peripheral access for apheresis. Patients must also have adequate mononuclear cells for CAR T cell manufacturing；
• Staining of MSLN must be greater than 50% of the cells in the tumor tissue and with apparent expression in the membrane. PD-L1 expression must be positive. Tissue obtained for the biopsy must be ≤1 year prior to enrollment for screening, not have been previously irradiated or exposed to chemotherapy. If unavailable, new tissue material from a recently obtained surgical or diagnostic biopsy is mandatory for this trial；
• Satisfactory organ and bone marrow function as defined by the following:
• Adequate bone marrow function in the opinion of the Investigator for lymphocyte-depleting chemotherapy: absolute neutrophil count must be greater than ≥ 1.5×109/L, lymphocyte count must be greater than ≥ 0.5×109/L, platelets must be greater than ≥ 90×109/L, hemoglobin must be greater than ≥ 90g/L without transfusion within 7 days or dependency on EPO;
• Total bilirubin must be less than or equal to two times (≤2.0x) the institutional normal upper limit; transaminases, serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST), must be less than or equal to 2.5 times (≤2.5x) the institutional normal upper limit (≤2.5x if there is hepatic metastasis);
• Creatinine must be less than or equal to one and one half times (≤ 1.5x) the institutional normal upper limit or eGFR ≥ 60ml/min/1.73m\^2 \[eGFR=186×（age）-0.203×SCr-1.154（mg/dl）,for female the eGFR shoud be timed by 0.742\];
• International normalized ratio (INR) or the PT is not greater than one and one half times (≤ 1.5) the upper limit of normal;
• Lung function: ≤ CTCAE grade 1 dyspnea and SaO2≥ 91%
• Cardiac function: cardiac ejection fraction (LVEF) must be greater than fifty percent (≥50%) by echocardiogram or MUGA one month before enrollment.
• Subjects must have measureable disease as defined by RECIST 1.1 criteria;

You may not qualify if:

• Prior therapy with targeted therapy or cell therapy against MSLN；
• Prior therapy with any gene therapy (including CAR-T cell therapy) or any T cell therapy home and abroad；
• Active bacteria, viral or fungal infection, and not contained after anti-infective therapy (positive results in the blood ≤72 hours before infusion);
• Patient is positive for Syphilis, Human Immunodeficiency Virus (HIV) , active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA (qualitative) is detected);
• Patient has a medical condition such as autoimmune disease or organ transplantation that requires chronic systemic steroid therapy or requires any other form of immunosuppressive medication;
• History of severe cardiac or pulmonary disease, including hypertension that cannot be controlled by medication, and any of the conditions occurred within the past 6 months: congestive heart failure (New York Heart Association functional classification ≥3), cardiac angioplasty and stents, myocardial infarction, unstable angina, or other clinically significant heart disease；
• Detectable clinically relevant central nervous system (CNS) metastases and/or pathology such as epilepsy/seizure, brain Ischemia/ hemorrhage, dementia, cerebellar disease, or autoimmune disease affecting central nervous system；
• Patient has a history or current evidence of any condition such as neurotic, psychiatric, immune, metabolic and infectious disease, on any therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator；
• Patient has a known history of a hematologic malignancy, or of another malignant primary solid tumor concurrently, with the exception of :
• Patients with in situ cervical cancer or breast cancer with no evidence of disease for ≥ 3 years after curative treatments;
• Patients who underwent successful definitive resection of in situ cancer with no evidence of disease for ≥5 years;
• Has had chemotherapy, radioactive, small molecules, biological cancer therapy, immunotherapy or other investigational drugs within 4 weeks prior to the initiation of the study；
• Pregnant or breastfeeding women;
• Investigators think that patient has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study and cooperation with the requirements of the trial, uncontrolled medical, psychological, familial, sociological, or geographical conditions, or is not in the best interest of the patient to participate.

Sponsors & Collaborators

• Shanghai Cell Therapy Group Co.,Ltd: lead
• Shanghai 10th People's Hospital: collaborator

Study Sites (1)

Shanghai Tenth people's Hospital

Shanghai, Shanghai Municipality, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Ovarian Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Qing Qu

  Shanghai 10th People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Juemin Fang

CONTACT

021-66302521; 435254611@qq.com

Study Design

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

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: August 7, 2020
• Study Start: March 26, 2020
• Primary Completion: March 1, 2021
• Study Completion: June 1, 2022
• Last Updated: August 7, 2020

Record last verified: 2020-08

Locations

CN (1)