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

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

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.

Study Overview

• Status: Unknown
• Conditions: Non-small Cell Lung Cancer; Lung Neoplasm Malignant
• Intervention / Treatment: Biological: CAR-T Cells; Combination product: CAR-T combining PD-1 Knockout; Biological: PD-1 knockout; Drug: PD-1 mAb; Other: Sham control

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 Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • First Affiliated Hospital of Guangdong Pharmaceutical University
      • Contact: Guobiao Huang; Phone Number: 86-20-39352064; Email: 153706227@qq.com
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • Professor Size Chen
      • Contact: Size Chen, MD,PhD; Phone Number: +8613720956393; Email: 13720956393@139.com
      • Principal Investigator: Yiguang Lin, MD, PhD
      • Sub-Investigator: Micheal Yin, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAR-T; Anti-MUC1 CAR-T cells will be prepared ex vivo and infused back to the patients.	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.
Experimental: 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.	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
Experimental: PD-1 knockout; PD-1 knockout Engineered T cells will be prepared ex vivo and 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
Active Comparator: 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.	Drug: PD-1 mAb; Patients will be treated with an identical course with a FDA approved monoclonal antibody against PD-1; Other Names: Keytruda
Placebo Comparator: Sham Control; Patient's T cells will be separate without genetic or engineered modification ex vivo and infused back to the patients.	Other: Sham control; Patient's T cell will treated ex vivo with modification and then infused back in a similar time course.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Guangdong Pharmaceutical University
• Collaborators: University of Technology, Sydney; Guangzhou Anjie Biomedical Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2018
• Primary Completion (Anticipated): January 31, 2021
• Study Completion (Anticipated): January 31, 2022

Study Registration Dates

• First Submitted: April 26, 2018
• First Submitted That Met QC Criteria: May 3, 2018
• First Posted (Actual): May 16, 2018

Study Record Updates

• Last Update Posted (Actual): May 16, 2018
• Last Update Submitted That Met QC Criteria: May 3, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Non-small cell lung cancer; CAR-T cell therapy; MUC+; PD-1 Knockout
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 2018-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No