Anti-GPC3 CAR T for Recurrent or Refractory Lung Squamous Cell Carcinoma

August 23, 2016 updated by: CARsgen Therapeutics Co., Ltd.

Preliminary Clinical Study of Autologous T Cells Modified Chimeric Antigen Receptor (CAR) Targeting GPC3 for the Treatment of Recurrent or Refractory Lung Squamous Cell Carcinoma

The purpose of this study is to observe and confirm the safety, tolerance and cell pharmacokinetics of lentivirus-transduced CAR-GPC3 T cells (CAR-GPC3 T cells targeting GPC3)

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

A single-center, open-label pilot study to determine the safety, tolerance and engraftment potential of CAR-GPC3 T cells in subjects with GPC3+ positive lung squamous cell carcinoma.

Primary objectives:

Observe and determine the safety and tolerance in escalating dose infusion of CAR-GPC3 T cells (CAR T cells targeting GPC3) transduced with the lentiviral vector, and the survival of the CAT-GPC3 T cells in vivo, referred to as engraftment potential.

Secondary objectives:

The following indexes are monitored for curative effect of CAR-GPC3 T cells on lung squamous cell carcinoma:

  1. Objective response rate (ORR), is defined as the ratio of patients diagnosed as partial remission (PR) to complete remission (CR) according to RECIST 1.1 criteria.
  2. Progression free survival (PFS), is defined as the duration from baseline to PD (audited and confirmed by independent imaging), or to the day of any death event. The earlier one shall prevail.
  3. Time to tumor progression (TTP), is defined as the duration from baseline to disease starts to get worse or spreads to other parts of the body.
  4. Overall survival (OS), is defined as the time period from the 1st day of treatment to the day of death for any reason. For patients who are still alive at the data analysis day, OS data is subject to the last confirmed time of survival patients.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200030
        • Recruiting
        • Shanghai Chest Hospital,Shanghai Jiaotong University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Men or women aged 18~70 years old
  2. Subjects are diagnosed as refractory, recurrent ,metastatic, advanced lung squamous cell carcinoma by histological and cytological methods including specific lesion-targeted brush biopsy, lavage and fine needle aspiration;
  3. Have at least one new measurable tumor lesion compared with previous irradiated region
  4. Tumor tissues samples confirmed as GPC3-positive
  5. Expected survival≥12 weeks
  6. ECOG scored as 0-1 or KPS grading > 80
  7. ANC≥1500/nm3
  8. PLT≥100000/mm3
  9. Hb≥9.0g/dL
  10. Serum creatinine≤2.5mg/dL，CCR≥50ml/min (renal malfunction defined as CCR<50ml/min according to Cockroft-Gault formula)
  11. ALT and AST≤2.5ULN; for liver metastasis，ALT and AST ≤5ULN
  12. Serum TBiL≤3.0mg/dL, TBiL≤2.5ULN
  13. PT: INR < 1.7 or extended PT to normal value < 4s
  14. Adequate venous access for apheresis or venous blood collection, and no other contraindication of blood cell separation
  15. Patients with willingness to be in this study and able to provide informed consent
  16. Capable of receiving treatment and follow up, included subjects are required to receive treatment in the enrolled centre
  17. Women of childbearing age are required to take acceptable measures to minimize the possibility of pregnancy during whole session. Women of childbearing age must have negative results of serum or urine tests within 24 hours prior to infusion. Women subjects must not be in lactation;

Exclusion Criteria:

  1. CAR-T positive rate < 10%
  2. pregnant women or women in lactation
  3. active HBV or HCV infection
  4. HIV/AIDS infection
  5. active infection

  6. previously suffered from diseases or concurrent diseases as followed：

    • patients confirmed as severe autoimmune diseases in long-term (over 2 months) need of systemic immune inhibitors (steroid) or as immune-mediated symptomatic diseases including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), autoimmune vasculitis (for example, Wegener's granulomatosis)
    • subjects with previous diagnosis as motor neurone disease caused by autoimmunity
    • subjects previously suffered from toxic epidermal necrolysis (TEN)
    • subjects with any mental diseases including dementia, mental status change that may impinge the understanding and performance of informed consent and related questionnaire
    • subjects with severe, uncontrollable diseases judged by investigators that may hinder them receiving this treatment
    • subjects with previously active malignant tumors including basal or squamous skin cancer, superficial bladder cancer, and in situ breast carcinoma within 5 years who had been completely cured without the need of follow-up treatment are not excluded.
  7. during ongoing treatment using systemic steroid or steroid inhalants
  8. previous treatment used gene therapy products
  9. previous experience of immunotherapies including CIK, DC, DC-CIK, LAK for the treatment of cancer
  10. allergic to immunotherapies or related drugs
  11. patients in need of treatment for heart disease with ≥2 NYHA or for poor controlled hypertension
  12. subjects with unstable or active peptic ulcer or alimentary tract hemorrhage
  13. subjects with previous organ transplantation or ready for organ transplantation
  14. subjects in need of anticoagulant therapy treatment (warfarin or heparin)
  15. subjects judged by investigators as not appropriate for this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CAR-GPC3 T cells

Intravenous infusion with escalating dose is adopted in this study.

Total dosage: 1 x 10^5 - 2 x 10^9 CAR-GPC3 T cells/kg

The next dose and interval depends on the response of the subject to previous dose.

Lymphodepletion:

Fludarabine: 30 mg/m^2/day x 4 days; Cyclophosphamide: 500 mg/m^2/day x 2 days. Adjustment is in discretion of the investigator based on individual response.
Genetic: CAR-GPC3 T Cells
Intravenous infusion of CAR-GPC3 T cells is conducted 1 - 2 days following lymphodepletion.
Other Names:
  • Anti-GPC3 CAR T
  • CAR T cells redirected to Glypican-3
Drug: Fludarabine
30 mg/m^2/day x 4 days
Drug: Cyclophosphamide
500 mg/m^2/day x 2 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerance: Occurrence of study related adverse events
Time Frame: 24 weeks
Occurrence of study related adverse events, defined as laboratory toxicities and clinical events that are possibly, likely or definitely related to study treatment at any time from the infusion until week 24. This will include infusive toxicity, and any toxicity possibly related to the CAR-GPC3 T cells.
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Engraftment: the DNA vector copies per mL blood of CAR-GPC3 T cells
Time Frame: 2 years
The DNA vector copies per mL blood of CAR-GPC3 T cells on week 4 after the first infusion by Q-PCR. Q-PCR for CAR-GPC3 vector sequences will also be performed after infusion thereafter until any 2 sequential tests are negative documenting loss of CAR-GPC3 T cells within 2 years.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

CARsgen Therapeutics Co., Ltd.

Investigators

  • Principal Investigator: Jiang Liyan, MD, Shanghai Chest Hospital,Shanghai Jiaotong University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2016

Primary Completion (Anticipated)

October 1, 2017

Study Completion (Anticipated)

April 1, 2019

Study Registration Dates

First Submitted

August 9, 2016

First Submitted That Met QC Criteria

August 23, 2016

First Posted (Estimate)

August 24, 2016

Study Record Updates

Last Update Posted (Estimate)

August 24, 2016

Last Update Submitted That Met QC Criteria

August 23, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CG1003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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