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

NCT03525782 | Unknown Phase 1

• 1 other identifier: 2018-006
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

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.

Conditions

Lung Neoplasm Malignant; Non-small Cell Lung Cancer

Keywords

CAR-T cell therapy; MUC+; PD-1 Knockout; Non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Response Rate

  6 months

• Overall Survival - OS

  Up to 24 months

• Progression free survival - PFS

  Up to 12 months

• Median CAR-T cell persistence

  4 years

Study Arms (5)

CAR-T

EXPERIMENTAL

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

Biological: CAR-T Cells

CAR-T combining PD-1 knockout

EXPERIMENTAL

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; Combination Product: CAR-T combining PD-1 Knockout; Biological: PD-1 knockout

PD-1 knockout

EXPERIMENTAL

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

Biological: PD-1 knockout

PD-1 mAb

ACTIVE COMPARATOR

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

Sham Control

PLACEBO COMPARATOR

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

Other: Sham control

Interventions

CAR-T Cells BIOLOGICAL

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.

CAR-T; CAR-T combining PD-1 knockout

CAR-T combining PD-1 Knockout COMBINATION_PRODUCT

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

CAR-T combining PD-1 knockout

PD-1 knockout BIOLOGICAL

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

CAR-T combining PD-1 knockout; PD-1 knockout

PD-1 mAb DRUG

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

Also known as: Keytruda

PD-1 mAb

Sham control OTHER

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

Sham Control

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Guangdong Pharmaceutical University: lead
• Guangzhou Anjie Biomedical Technology Co., Ltd.: collaborator
• University of Technology, Sydney: collaborator

Study Sites (3)

First Affiliated Hospital of Guangdong Pharmaceutical University

Guangzhou, Guangdong, 510080, China

RECRUITING

Professor Size Chen

Guangzhou, Guangdong, 510080, China

RECRUITING

Professor Size Chen

Guangzhou, Guangdong, 510080, China

RECRUITING

Related Publications (1)

• Barr T, Ma S, Li Z, Yu J. Recent advances and remaining challenges in lung cancer therapy. Chin Med J (Engl). 2024 Mar 5;137(5):533-546. doi: 10.1097/CM9.0000000000002991. Epub 2024 Feb 7.

  PMID: 38321811 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Immunotherapy, Adoptive; pembrolizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 26, 2018
• First Posted: May 16, 2018
• Study Start: February 1, 2018
• Primary Completion: January 31, 2021
• Study Completion: January 31, 2022
• Last Updated: May 16, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)