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

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Clinical Study of Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for Patients With Advanced Non-small Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03525782
• Other study ID #: 2018-006
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 1, 2018
• Est. completion date: January 31, 2022

Study information

• Verified date: May 2018
• Source: The First Affiliated Hospital of Guangdong Pharmaceutical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: January 31, 2022
• Est. primary completion date: January 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasm Malignant
• Lung Neoplasms
• Neoplasms
• Non-small Cell Lung Cancer

Intervention

Biological:
• CAR-T Cells
Using the T cells from the patients to produce anti-MUC1 CAR-T Cells and then the cells will be infused back to the patients.

Combination Product:
• CAR-T combining PD-1 Knockout
Using the T cells from the patients to prepare anti-MUC1 CAR-T Cells and PD-1 knockout T cells, then the cells will be infused back to the patients

Biological:
• PD-1 knockout
Using the T cells from the patients to prepare PD-1 knockout T cells, then the cells will be infused back to the patients

Drug:
• PD-1 mAb
Patients will be treated with an identical course with a FDA approved monoclonal antibody against PD-1

Other:
• Sham control
Patient's T cell will treated ex vivo with modification and then infused back in a similar time course.

Locations

Country	Name	City	State
China	First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou	Guangdong
China	Professor Size Chen	Guangzhou	Guangdong
China	Professor Size Chen	Guangzhou	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou Anjie Biomedical Technology Co;LTD, University of Technology, Sydney

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0	Safety and tolerability of dose of CART-cells and PD-1 Knockout T cells will be assessed using CTCAE v4.0.	approximately 6 months
Secondary	Response Rate	Will be assessed according to the revised RECIST guideline v1.1	6 months
Secondary	Overall Survival - OS	Measure the time from enrollment to death	Up to 24 months
Secondary	Progression free survival - PFS	Time from enrollment to date of first documented progression or date of death.	Up to 12 months
Secondary	Median CAR-T cell persistence	Will be measured by quantitative RT-PCR	4 years