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Advanced Solid TumorPhase 1/2NCT03182816

CTLA-4 and PD-1 Antibodies Expressing EGFR-CAR-T Cells for EGFR Positive Advanced Solid Tumor

A Phase 1/2 study testing anti-CTLA-4/PD-1 expressing EGFR-CAR-T in people with Advanced Solid Tumor, run by Shanghai Cell Therapy Research Institute at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a single-arm, open-label, one center clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to express immune checkpoint antibodies (CTLA-4 and PD-1) and chimeric antigen receptor targeting epidermal growth factor receptor (EGFR-CAR) in adult patients with EGFR… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Advanced Solid Tumor
What is being tested?
anti-CTLA-4/PD-1 expressing EGFR-CAR-T
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteChina
Study dates
7 Jun 2017to 20 Apr 2019
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with relapsed or refractory advanced solid malignancies (diagnosed by histology or cytology detection).
  • Progressive disease and no response after at least second-line therapy.
  • Gender unlimited, age from 18 years to 80 years.
  • Life expectancy ≥3 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Adequate venous access for peripheral blood mononuclear cell (PBMC) apheresis, and no other contraindications.
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  • Immunohistochemistry (IHC) score of EGFR on tumor tissue ≥1+.
  • Adequate hepatic function, renal function and bone marrow function (withhin 7 days before enrollment): white blood cell (WBC) ≥3.0×10^9/L; platelet ≥100×10^9/L; hemoglobin ≥90 g/L; lymphocyte ≥0.7×10^9/L; total bilirubin ≤2 times the upper limit of the normal value; alanine aminotransferase and aspartate transaminase(ALT and AST) ≤2.5 times the upper limit of the normal value; serum creatinine ≤1.5 times the upper limit of the normal value.
  • There is no other treatments (chemotherapy, radiotherapy, etc.) within four weeks before enrollment.
  • There is at least one measurable tumor lesion.
  • Patients have adequate ability to understand, sign informed consents and take part in the clinical research voluntarily.
  • Female patients in child bearing period must have evidence of negative pregnancy test, and agree to take effective contraceptive measures until 4 months after cells infusion.

Who cannot join

  • Patients with two or more kinds of tumors.
  • Patients with active viral or bacterial infection, and have failed to be controlled by anti-infective treatment.
  • Patients with seropositive reponse of Human immunodeficiency virus (HIV) and syphilis, or fail to control the hepatitis B virus or hepatitis C virus infection.
  • Patients with active rheumatic diseases, organ transplantation and other diseases affecting the immune system seriously.
  • Patients with severe heart and lung dysfunction.
  • Patients with severe chronic diseases of kidney, liver and other important organs.
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  • Patients with any other serious illnesse that the investigators consider it will may affect the patient's treatments, follow-up or assessment, including any uncontrolled clinically significant neurological or psychiatric disorders, immunoregulatory diseases, metabolic diseases, infectious diseases and so on.
  • Patients who take part in clinical trials of other drugs or biological therapy at present or within 30 days before enrollment.
  • Patients who need long-term use of immunosuppressive drugs or patients who are undergoing treatment of autoimmune diseases.
  • Patients who need long-term use of glucocorticoid.
  • Women patients in gestation period or suckling period.

Trial locations and contacts

1 site in 1 country.

Zhiwei Zhang, Ph.D contact

0086-021-39595338

zhangzw@shcell.com

China1 site, 1 recruiting

  • Ningbo No.5 Hospital (Ningbo Cancer Hospital)

    Ningbo, Zhejiang, 315201

    Bi Wang, 0086-0574-86689113, biwang0217@126.com

    Jiangtao Wang

    Recruiting

Other trials in China

About this study

Official title: A Clinical Study of CTLA-4 and PD-1 Antibodies Expressing EGFR-CAR-T Cells for Patients With EGFR Positive Advanced Solid Tumors

This is a single-arm, open-label, one center clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to express immune checkpoint antibodies (CTLA-4 and PD-1) and chimeric antigen receptor targeting epidermal growth factor receptor (EGFR-CAR) in adult patients with EGFR positive, advanced recurrent or refractory malignant solid tumors.

Read the detailed description

This study will be conducted using a phase I/II trial design to assess the efficacy and safety of the CTLA-4 and PD-1 antibodies expressing EGFR-CAR-T for patients with EGFR positive advanced recurrent or refractory malignant solid tumors. EGFR-CAR-T can specificly and effectively kill the EGFR positive cancer cells, CTLA-4 and PD-1 antibodies are secreted from the CAR-T cells could improve immunosuppression microenvironment, new CAR-T cells contain the advantages of CAR-T and immune checkpoint inhibitor, which is a promising therapeutic method for advanced solid tumors.

The new CAR-T therapy is applied to clinical practice as bellow. T cells are prepared from peripheral blood mononuclear cells (PBMC) by leukapheresis, then activated and engineered to express CTLA-4 and PD-1 antibodies and chimeric antigen receptor targeting EGFR. Cells are proliferated in culture and returned to the patients by venous transfusion therapy. A total of 40 patients may be enrolled in the study. The total duration of the study is expected to be approximately 24 months.

Being tested
anti-CTLA-4/PD-1 expressing EGFR-CAR-T
Keywords
epidermal growth factor receptor, CTLA-4, PD-1, chimeric antigen receptor T cells, solid tumor
Medical subject headings
Diabetes Mellitus, Insulin-Dependent, 12

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • anti-CTLA-4/PD-1 expressing EGFR-CAR-TBiological

    Also called CTLA-4 and PD-1 antibodies expressing EGFR-CAR-T cells

    Every cycle, peripheral blood mononuclear cells (PBMC) are collected on day 0, CAR-T cells are cultured in a GMP standard workshop. Patients are given a three-day regimen of chemotherapy consisting of cyclophosphamide aimed to deplete the lymphocytes before cells infusion. Then the patients will receive an i.v.gtt infusion of CTLA-4 and PD-1 antibodies expressing EGFR-CAR-T cells at (2-5) ×10^7 cells/kg from day 18 to day 19 (±2 days). 2 cycles are regarded as a treatment period.

Study groups in NCT03182816
Study groupRoleWhat they receive
anti-CTLA-4/PD-1 expressing EGFR-CAR-TExperimentalThis study have only one arm that is anti-CTLA-4/PD-1 expressing EGFR-CAR-T group. All patients with advanced solid tumor will take part in the screening, who matching all the conditions will be chosen for the treatment using CTLA-4 and PD-1 antibodies expressing EGFR-targeted CAR-T cells. New CAR-T cells are cultured from PBMC and returned to the patients by venous transfusion.
Receives: Biological: anti-CTLA-4/PD-1 expressing EGFR-CAR-T

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of treatment-related adverse events as assessed by CTCAE v4.0

    Determine treatment-related adverse events of the immunotherapy with common toxicity criteria for adverse effects (CTCAE) version 4.0.

    Measured: 2 years

Secondary outcomes (3)

  1. The response evaluation of of the treatment for advanced solid tumors

    The efficacy of the treatment is assessed according to the response evaluation criteria in solid tumor version 1.1 (RECIST1.1), which is defined as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).

    Measured: 2 years

  2. Progression free survival

    Progression free survival is defined as the time from the day in which the patient is enrolled to the date on which tumor progresses or the date on which the patient dies for any cause.

    Measured: 2 years

  3. Overall survival

    Overall survival is defined as the time from the day in which the patient is enrolled to the date on which the patient dies for any cause.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jun 2017
  2. Study start7 Jun 2017 (estimated)
  3. Primary completion20 Jan 2019 (estimated)
  4. Study completion20 Apr 2019 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03182816
Sponsor's protocol ID
H2017-03-P01
Status last verified
Jun 2017
First submitted
5 Jun 2017
Last updated
9 Jun 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Zhang Y, Zhang Z, Ding Y, Fang Y, Wang P, Chu W, Jin Z, Yang X, Wang J, Lou J, Qian Q. Phase I clinical trial of EGFR-specific CAR-T cells generated by the piggyBac transposon system in advanced relapsed/refractory non-small cell lung cancer patients. J Cancer Res Clin Oncol. 2021 Dec;147(12):3725-3734. doi: 10.1007/s00432-021-03613-7. Epub 2021 May 25.

    PubMed 34032893

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing anti-CTLA-4/PD-1 expressing EGFR-CAR-T in people with Advanced Solid Tumor, run by Shanghai Cell Therapy Research Institute at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 9 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Zhiwei Zhang, Ph.D (0086-021-39595338, zhangzw@shcell.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of treatment-related adverse events as assessed by CTCAE v4.0 (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03182816, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2017.

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