Autologous CAR-T/TCR-T Cell Immunotherapy for Solid Malignancies

EGFRvIII/DR5/NY-ESO-1/Mesothelin CAR-T/TCR-T Cells Immunotherapy for Solid Malignancies

This is a single arm, open-label, uni-center, phase I-II study to evaluate the safety and effectiveness of CAR-T/TCR-T cell immunotherapy in treating with different malignancies patients.

Study Overview

• Status: Recruiting
• Conditions: Glioma; Gastric Cancer; Hepatoma; Esophagus Cancer
• Intervention / Treatment: Biological: CAR-T/TCR-T cells immunotherapy

Detailed Description

The study is a multi-target gene-modified immunotherapy. CAR-T/TCR-T cells include four different tumor-specific antibody.They are as following:anti-NY-ESO-1 antibody foresophagus cancer;anti-DR5 antibody for hepatoma;;anti-EGFR vIII antibody for hepatoma and glioma;anti-Mesothelin antibody for gastric cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: ZHONG HUA YANG; Phone Number: +8618938688105 +8618938688105; Email: zh.yang@bindebio.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • HeNan Provincial People's Hospital
      • Contact: Shuangyin Han; Phone Number: +8613203710057; Email: hansyzzu@163.com
      • Contact: Chun-Xiao Ma; Phone Number: +8615038287266; Email: chxma@126.com
      • Principal Investigator: Shuangyin Han
      • Principal Investigator: Chun-Xiao Ma

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:

1. Patients must be willing to sign an informed consent.
2. Male or female patients aged 18 to 70 years .
3. Estimated survival of ≥ 12 weeks.
4. Pathological sections with positive expression of NY-ESO-1, Mesothelin, EGFRvIII and DR5 was confirmed by biopsy IHC test within 12 months.If NY-ESO-1 is positive expression ,positive HLAA*0201 is required at the same time.
5. Solid tumor must have at least one measureable disease according to RECIST 1.1.
6. Routine blood test#hemoglobin>=90 g/L; platelet>=50×10^9/L.
7. Liver function:ALT and AST≤2.5 times upper limits of normal (If the tumor infiltration is the main cause of abnormal liver function ,ALT and AST≤5 times upper limits of normal); bilirubin<2.0 mg/dL.
8. Renal function:BUN: 9-20mg / dl; serum creatinine≤ 1.5 times upper limits of normal; endogenous creatinine clearance rate≥50 ml/min .
9. Negative serum antibody for EBV, CMV, HIV , syphilis, HBVa nd HCV.
10. Cardiac function: stable hemodynamic and left ventricular ejection fraction (LVEF)>=55%.
11. ECOG score:0-1.
12. Adequate venous access for apheresis, and no other contraindications for leukapheresis .
13. Women of child-bearing age must have evidence of negative pregnancy test. Subjects of reproductive potential must agree to use acceptable birth control methods within 1 year after treatment, as described in protocol.
14. Subjects with hypertension/diabetes must be stable blood pressure/blood glucose or ≤CTCAE 1 level 2 weeks before the screening.

In addition to the above criteria for inclusion, the following criteria shall be met according to the indications:

Patients with glioblastoma：

1. First disease progression or disease recurrence (≥ 1 cm and ≤ 5 cm) of a supratentorial WHO grade IV malignant glioma (GBM or gliosarcoma) based on imaging studies with measurable disease.
2. EGFRvIII, the target antigen, must be identified on tumor tissue by IHC or PCR, i.e. EGFRvIII positive via pathology report.
3. Insensitivity to chemoradiotherapy or chemoradiotherapy failure after operation molecular pathology.
4. Refused to receive radiotherapy or chemotherapy treatment.

Patients with liver cancer

1. DR5 or EGFRvIII positive via pathology report.
2. Untreatable by surgery ; Or postoperative recurrence ;Or no effective treatment.
3. Liver function：child-pugh A grade or child-pugh B grade.

Patients with gastric cancer

1. Mesothelin positive via pathology report.
2. The pathological stage：IIIA～IV.
3. chemoradiotherapy failure
4. Refused or unable to get surgery.

Patients with esophageal cancer

1. NY-ESO-1 positive via pathology report and HLA-A*0201 positive in blood.
2. Refuse or unable to get surgery.
3. Postoperative recurrence or chemoradiotherapy failure.

Exclusion Criteria:

1. ECOG≥2.
2. malignant tumor cells with T cell origin via pathology test.
3. Organ failure: stage III or IV congestive heart failure; Renal failure and uremia; respiratory failure; disturbance of consciousness.
4. Acute or chronic GVHD after allogeneic hematopoiesis; Or being treated for GVHD; Or hormone or immunosuppressant used within 30 days
5. steroid hormoneswere used before and after blood collection and infusion
6. Patients with HIV infection or active hepatitis
7. Uncontrolled active infection.
8. Enrolled to other clinical study in the last 4 weeks.
9. Patients with systemic auto-immune disease or immunodeficiency.
10. Patients with neuropathy or psychosis, including dementia or epilepsy, or history of psychotropic substance abuse, or other substantial lesions that may increase central neurotoxicity.
11. Concomitant with the second tumor or other malignant tumors.
12. Patients with bone metastases are at risk of a pathological fracture resulting in paraplegia or life threatening.
13. Live attenuated vaccine was administered within 4 weeks prior to blood collection.
14. Blood oxygen saturation is maintained by oxygen inhalation.
15. Received major surgery within 2 weeks prior to screening ;Or Plan to receive surgery during study or within 2 weeks after injection.
16. Other patients that researchers considered unsuitable for inclusion.

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: CAR-T/TCR-T cells immunotherapy; Enrolled patients will receive CAR-T cell immunotherapy with several different specific Chimeric antigen receptors aiming at different antigens respectively by infusion.	Biological: CAR-T/TCR-T cells immunotherapy; According to tumor burden and other conditions, patients will be treated with cyclophosphamide or fludarabine,then,CAR-T cells will be infused 48-72 hours later.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events evaluated with NCI CTC AE, version 4.0	Safety evaluation	48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	Clinical response to T-cell infusion, especially change of tumor volume will be evaluated by comparing disease identified by computed tomography, magnetic resonance imaging.	48 months

Collaborators and Investigators

• Sponsor: Shenzhen BinDeBio Ltd.
• Collaborators: Henan Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Anticipated): May 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: May 6, 2019
• First Submitted That Met QC Criteria: May 6, 2019
• First Posted (Actual): May 8, 2019

Study Record Updates

• Last Update Posted (Actual): February 4, 2021
• Last Update Submitted That Met QC Criteria: February 3, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: 2019BDB016

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