PD-1 Antibody Expressing CAR-T Cells for EGFR Family Member Positive Advanced Solid Tumor

A Clinical Study of PD-1 Antibody Expressing CAR-T Cells for EGFR Family Member Positive Advanced Solid Tumor

To evaluate the safety and effectiveness of cell therapy using herinCAR-PD1 cells to treat advanced cancer.

Individuals greater than or equal to 18 years of age and less than or equal to 70 years of age who have been diagnosed with relapsed or refractory cancer that has not responded to or has relapsed after standard treatment.

Study Overview

• Status: Unknown
• Conditions: Advanced Malignancies; PD-1 Antibody; CAR-T Cells
• Intervention / Treatment: Biological: HerinCAR-PD1 cells

Detailed Description

A total of 20 patients may be enrolled over a period of 1-2 years.

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

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Ningbo, Zhejiang, China
      • Recruiting
      • Ningbo No.5 Hospital (Ningbo Cancer Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18~80 years old, male or female;
2. Life expectancy≥6 months;
3. ECOG score: 0-2;
4. Advanced Solid Tumor were diagnosed by histology and cytology;
5. Enough venous channel,no other contraindications to the separation and collection of white blood cells;
6. Immunohistochemistry and RT-PCR technology will be used to determine the positive EGFR family (including EGFR, HER2, HER4) and EGFRVIII、IGF1R protein. At least one protein expressed in immunohistochemical tumor tissue should be no less than grade 2 or 2+ scores. The levels of protein are defined as follows: (according to cell staining) : grade 0: without staining; grade 1: 1-25%; grade 2: 26-50% and grade 3: 51-100%; (According to the intensity): negative; 1+; 2+ and 3+;
7. Laboratory examination: white blood cell≥3 x 10*9/L, blood platelet count≥60 x10*9/L, hemoglobin≥85g/L; lymphocyte ≥0.7×109/L, total bilirubin less than 2.5 times of the normal level; ALT and AST less than 2.5 times of the normal level; serum creatinine less than 1.5 times of the normal level；
8. Signed informed consent；
9. Women of child-bearing age must have evidence of negative pregnancy test and be willing to practice birth control after 4 months following the cells transfusion.
10. Disease progression and the current treatment is invalid.
11. The treatment effect is not ideal after receiving 2 line therapy at least and willing to join in clinical trials

Exclusion Criteria:

1. Expected Overall survival < 6 months;
2. Patients with uncontrolled hypertension,unstable coronary disease (uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (> Class II, NYHA), or myocardial infarction within 6 months.
3. Abnormal lung function: FEV (forced expiratory volume) < 30% prediction, DLCO (diffusing capacity of the lung for carbon monoxide) < 30% prediction, blood oxygen saturation < 90%;
4. Other serious diseases: nervous, mental disorders, immune regulatory diseases, metabolic diseases, infectious diseases, etc;
5. Unable or unwilling to provide informed consent, or fail to comply with the test requirements.
6. Uncontrolled active infection.
7. Serious chronic disease of critical organs such as kidney and liver. Kidney function more than CKD stage I,and liver function less than the Child - Pugh class B;
8. Long-term use or being used of immunosuppressive drugs with autoimmune diseases
9. Glucocorticoid is needed in a long term.
10. Currently (within 30 days) enrolled in another clinical trial.
11. Pregnancy or breastfeeding women.

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: HerinCAR-PD1 cells; Patients will receive 3 cycles of HerinCAR-PD1 cells treatment.	Biological: HerinCAR-PD1 cells; herinCAR-PD1 cells transfusion: (1-5×107/kg herinCAR-PD1 + physiological saline + 0.25% human alloalbumin) 300ml for each infusion. IV (in the vein) for each infusion, 2 cycles, each cycle received one infusions on day 21, 43.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	2 years
Objective response rate (ORR)	2 years
Disease control rate,(DCR)	2 years
Progress-free survival(PFS)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life	Questionnaire will be used.	2 years

Collaborators and Investigators

• Sponsor: Ningbo Cancer Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Anticipated): March 1, 2018
• Study Completion (Anticipated): July 1, 2018

Study Registration Dates

• First Submitted: August 15, 2016
• First Submitted That Met QC Criteria: August 16, 2016
• First Posted (Estimate): August 19, 2016

Study Record Updates

• Last Update Posted (Estimate): October 7, 2016
• Last Update Submitted That Met QC Criteria: October 6, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Advanced Malignancies; CAR-T Cells; PD-1 Antibody; EGFR family
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: NBWYKY2016-06-001/002/003

Plan for Individual participant data (IPD)

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