Antigen-specific T Cells Against Lung Cancer

• ClinicalTrials.gov Identifier: NCT03356808
• Recruitment Status: Unknown
• First Posted: November 29, 2017
• Last Update Posted: September 19, 2019
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Lung Cancer	Biological: Lung cancer-specific T cells	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multicenter Trial of Cancer Antigen-specific T Cells in the Treatment of Lung Cancer
• Actual Study Start Date: December 15, 2017
• Estimated Primary Completion Date: January 1, 2020
• Estimated Study Completion Date: December 31, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Safety of engineered T cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events [ Time Frame: 3 months ]
   Physiological parameter (measuring cytokine response)

Secondary Outcome Measures :

1. Persistence and proliferation of engineered antigen-specific T cells in patients [ Time Frame: 3 months ]
   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.
2. Anti-tumor effects [ Time Frame: 1 year ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Lung-Ji Chang, PhD; 86-075586725195; c@szgimi.org

Locations

China, Guangdong

Jinshazhou Hospital of Guangzhou University of Chinese Medicine; Recruiting

Guangzhou, Guangdong, China, 510415

Contact: Qichun Cai, MD 86-13802830754

Shenzhen Geno-immune Medical Institute; Recruiting

Shenzhen, Guangdong, China, 518000

Contact: Lung-Ji Chang, PhD 86-075586725195 c@szgimi.org

China, Yunnan

Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center; Recruiting

Kunming, Yunnan, China, 650000

Contact: Xun Lai, MD 13577096609 1729112214@qq.com

Sponsors and Collaborators

Shenzhen Geno-Immune Medical Institute

Investigators

• Principal Investigator: Lung-Ji Chang, PhD; Shenzhen Geno-Immune Medical Institute
• 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

More Information

• Responsible Party: Lung-Ji Chang, President, Shenzhen Geno-Immune Medical Institute
• ClinicalTrials.gov Identifier: NCT03356808
• Other Study ID Numbers: GIMI-IRB-17023
• First Posted: November 29, 2017
• Last Update Posted: September 19, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute:

Lung cancer; CAR-T; mesothelin; Muc1; GD2; MAGE-A4

Additional relevant MeSH terms:

Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases