Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for NSCLC

The First Affiliated Hospital of Guangdong Pharmaceutical University

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Lung Neoplasm Malignant; Non-small Cell Lung Cancer

Treatments: Biological: CAR-T Cells; Combination Product: CAR-T combining PD-1 Knockout; Biological: PD-1 knockout; Other: Sham control; Drug: PD-1 mAb

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03525782

2018-006

Details and patient eligibility

About

The study is to assess the safety and efficacy of the anti-MUC1 CAR T cells and /or PD-1 knockout engineered T cells for patients with advanced non-small cell lung cancer.

Full description

This is a combined phase 1 and 2 clinical study. The study is to assess the safety and efficacy of the anti-MUC1 CAR T cells and /or PD-1 knockout engineered T cells for patients with advanced non-small cell lung cancer. The treatment outcomes will be compared.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• MUC1 is expressed in malignancy tissues by immuno-histochemical (IHC).
• Eastern cooperative oncology group (ECOG) performance status of 0-1 or karnofsky performance status (KPS) score is higher than 60.
• Patients have a life expectancy > 12 weeks.
• Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis.
• Negative pregnancy test for females of child-bearing potentials.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: White blood cell count (WBC) ≥ 2500c/ml, Platelets ≥ 50×10^9/L, Hb ≥ 9.0g/dL, lymphocyte (LY) ≥ 0.7×10^9/L, LY% ≥ 15%, Alb ≥ 2.8g/dL, serum lipase and amylase < 1.5×upper limit of normal, serum creatinine ≤ 2.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal, serum total bilirubin ≤ 2.0mg/dL. These tests must be conducted within 7 days prior to registration.
• Signed informed consent form.

Exclusion criteria

• Number of T cells is less than 10% or the amplification of the T cells via artificial antigen presenting cell (aAPC) stimulation is less than 5 times.
• Patients with symptomatic central nervous system (CNS) involvement.
• Pregnant or nursing women.
• Known HIV infection.
• Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders.
• History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.
• Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
• Previously treatment with any gene therapy products.
• The existence of unstable or active ulcers or gastrointestinal bleeding. Patients with portal vein vascular invasion or extrahepatic, are excluded from this study.
• Patients with a history of organ transplantation or are waiting for organ transplantation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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60 participants in 5 patient groups, including a placebo group

CAR-T

Experimental group

Description:

Anti-MUC1 CAR-T cells will be prepared ex vivo and infused back to the patients.

Treatment:

Biological: CAR-T Cells

CAR-T combining PD-1 knockout

Experimental group

Description:

Anti-MUC1 CAR-T cells and PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.

Treatment:

Biological: PD-1 knockout

Combination Product: CAR-T combining PD-1 Knockout

Biological: CAR-T Cells

PD-1 knockout

Experimental group

Description:

PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.

Treatment:

Biological: PD-1 knockout

PD-1 mAb

Active Comparator group

Description:

Patients will be treated with a FDA approved monoclonal antibody for an identical course of treatment. This group will serve as PD-1 antibody treated group.

Treatment:

Drug: PD-1 mAb

Sham Control

Placebo Comparator group

Description:

Patient's T cells will be separate without genetic or engineered modification ex vivo and infused back to the patients.

Treatment:

Other: Sham control