Antigen-specific T Cells Against Lung Cancer

Multicenter Trial of Cancer Antigen-specific T Cells in the Treatment of Lung Cancer

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of cancer antigen-specific T cells targeting lung cancer. The cancer targeting antigens are identified through immunostaining of patient's cancer specimens. Another goal of the study is to learn more about the persistence and function of the ex vivo manipulated antigen-specific T cells in the body.

Study Overview

• Status: Unknown
• Conditions: Lung Cancer
• Intervention / Treatment: Biological: Lung cancer-specific T cells

Detailed Description

Lung cancer is a malignancy characterized by uncontrolled cell growth in tissues of the lung. There are two main types of lung cancer, small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). In 2012, lung cancer occurred in 1.8 million people and resulted in 1.6 million deaths worldwide. Common treatments include surgery, chemotherapy, and radiotherapy, but in relapsed cancer patients, such treatments often have limited successes.

In this study, the participant's peripheral blood mononuclear cells will be collected for antigen-specific T cell preparation, and/or modified using an advanced lentiviral vector system. Then the antigen-specific T cells, called engineered immune effectors (EIEs) or chimeric antigen receptor modified-T cells (CAR T), which can recognize specific molecules that are expressed by the lung cancer cells, are given back to the participant by intravenous infusion.

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of T cell immunotherapy targeting single or multiple cancer antigens. The lung cancer antigens include known tumor antigens such as MAGE-A1, MAGE-A4, MucI, GD2, and mesothelin, as well as novel cancer antigens. Another goal of the study is to learn more about the persistence and function of the specific CAR T cells in the body.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510415
      • Recruiting
      • Jinshazhou Hospital of Guangzhou University of Chinese Medicine
      • Contact: Qichun Cai, MD; Phone Number: 86-13802830754
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-immune Medical Institute
  • Yunnan
    • Kunming, Yunnan, China, 650000
      • Recruiting
      • Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center
      • Contact: Xun Lai, MD; Phone Number: 13577096609; Email: 1729112214@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with stage III, IV or relapsed lung cancer confirmed by histology and biopsy.
2. Age: ≥ 18 years and ≤ 80 years.
3. 4 weeks at least since last chemotherapy or radiotherapy and 2 weeks at least since last systemic steroid hormone and other immunosuppressive therapy.
4. Side Effects of Chemotherapy have subsided.
5. Cancer specific antigens are identified and shown to express at high levels (>2+) in malignant tissues by immuno-histochemical staining or flow cytometry.
6. Karnofsky/Lansky ≥ 50%.
7. Expected survival ≥ 6 weeks.

Initial hematopoietic conditions with

• neutrophils (ANC) ≥ 1×10^6/L;
• platelet (PLT) ≥ 1×10^8/L.

Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with

• serum creatinine ≤ 2×ULN;
• serum bilirubin ≤ 3×ULN;

• AST/ALT ≤ 5×ULN.

  10. Oxygen saturation ≥ 90%. 11. Written, informed consent obtained prior to any study-specific procedures.

Exclusion Criteria:

1. Airway obstruction caused by tumor.
2. History of epilepsy or other central nervous system diseases.
3. Patients who require systemic corticosteroid or other immunosuppressive therapy.
4. History of prolonged or serious heart disease during QT.
5. history of serious cyclophosphamide toxicity.
6. Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug or previous participation in any immune cell therapy study.

Inadequate liver and renal function with

• serum creatinine > 2.5 mg/dl;
• serum (total) bilirubin > 2.0 mg/dl;

• AST & ALT > 3 x ULN.

  8. Pregnant or lactating females. 9. Serious active infection during screening. 10. Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.

  11. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lung cancer-specific T cells; Peripheral blood mononuclear cells (PBMCs) of patients, who have cancer antigen identified lung cancer, will be obtained through apheresis, and T cells will be activated and ex vivo engineered.	Biological: Lung cancer-specific T cells; 1 infusion, for 1x10^6~1x10^7 cells/kg via IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of engineered T cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events	Physiological parameter (measuring cytokine response)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistence and proliferation of engineered antigen-specific T cells in patients	The expansion and functional persistence of ex vivo engineered T cells in the peripheral blood of patients will be examined on Day 7, 14, 21, 28, 60 and 90 after infusion.	3 months
Anti-tumor effects	Objective response, such as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.	1 year

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute
• Investigators: Study Director: Qichun Cai, MD, Jinshazhou Hospital of Guangzhou University of Chinese Medicine; Study Director: Xun Lai, MD, Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2017
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: November 24, 2017
• First Submitted That Met QC Criteria: November 24, 2017
• First Posted (Actual): November 29, 2017

Study Record Updates

• Last Update Posted (Actual): September 19, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: CAR-T; Lung cancer; GD2; mesothelin; Muc1; MAGE-A4
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: GIMI-IRB-17023

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