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

Phase 1

• Conditions: Lung Neoplasm Malignant; Non-small Cell Lung Cancer
• Interventions: Biological: CAR-T Cells; Drug: PD-1 mAb; Other: Sham control; Combination Product: CAR-T combining PD-1 Knockout; Biological: PD-1 knockout

• Registration Number: NCT03525782
• Lead Sponsor: The First Affiliated Hospital of Guangdong Pharmaceutical University

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2018-02-01
• Study First Submitted: 2018-04-26
• Status Verified: 2018-05
• Study First Submitted QC: 2018-05-03
• Last Update Submitted: 2018-05-03
• Study First Posted: 2018-05-16
• Last Update Posted: 2018-05-16
• Primary Completion: 2021-01-31
• Study Completion: 2022-01-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CAR-T	CAR-T Cells	Anti-MUC1 CAR-T cells will be prepared ex vivo and infused back to the patients.
CAR-T combining PD-1 knockout	CAR-T combining PD-1 Knockout	Anti-MUC1 CAR-T cells and PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.
CAR-T combining PD-1 knockout	CAR-T Cells	Anti-MUC1 CAR-T cells and PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.
CAR-T combining PD-1 knockout	PD-1 knockout	Anti-MUC1 CAR-T cells and PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.
PD-1 knockout	PD-1 knockout	PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.
PD-1 mAb	PD-1 mAb	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.
Sham Control	Sham control	Patient's T cells will be separate without genetic or engineered modification ex vivo and infused back to the patients.

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0	approximately 6 months	Safety and tolerability of dose of CART-cells and PD-1 Knockout T cells will be assessed using CTCAE v4.0.

Secondary Outcome Measures

Name	Time	Method
Progression free survival - PFS	Up to 12 months	Time from enrollment to date of first documented progression or date of death.
Overall Survival - OS	Up to 24 months	Measure the time from enrollment to death
Median CAR-T cell persistence	4 years	Will be measured by quantitative RT-PCR
Response Rate	6 months	Will be assessed according to the revised RECIST guideline v1.1

Trial Locations

Locations (2)

First Affiliated Hospital of Guangdong Pharmaceutical University; 🇨🇳 Guangzhou, Guangdong, China

Professor Size Chen; 🇨🇳 Guangzhou, Guangdong, China