AzTrials
AzTrials

Advanced Solid TumorPhase 1/2PAEMCMPASTNCT03615313

PD-1 Antibody Expressing mesoCAR-T Cells for Mesothelin Positive Advanced Solid Tumor

A Phase 1/2 study testing PD-1 antibody expressing mesoCAR-T cells 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 The sponsor has not verified this record for over two years, so it may be out of date.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
Search all trials

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 target mesothelin and express PD-1 antibodies in adult patients with advanced recurrent or refractory malignant solid tumors, which were positive expression of mesothelin. 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?
PD-1 antibody expressing mesoCAR-T cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteChina
Study dates
6 Aug 2018to 3 Dec 2020
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), including malignant mesothelioma, pancreatic cancer, bile duct cancer, ovarian cancer, lung cancer, gastric cancer, etc.
  • Patients who failed after second-line treatment, or who are unwilling to receive second-line treatment after failed to recieve first-line treatment.
  • Gender unlimited, age from 18 years to 80 years.
  • Life expectancy ≥ 3 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Adequate venous access for Peripheral blood mononuclear cell (PBMC) apheresis, and no other contraindications.
Show all 11Show fewer
  • Immunohistochemistry (IHC) score of mesothelin on tumor tissue ≥ 1+.
  • The requirements of laboratory examination: Neutrophilic granulocyte ≥ 1.0×10^9/L; Platelet ≥ 50×10^9/L; Hemoglobin ≥ 90g/L; total bilirubin ≤ 2 times the upper limit of the normal value; Alanine aminotransferase and Aspartate transaminase (ALT and AST) ≤ 2.5 times the upperlimit of the normal value (If there is liver metastasis, they should be ≤ 5 times the upperlimit of the normal value); Serum creatinine ≤ 1.5 times the upper limit of the normalvalue.
  • There is at least one measurable tumor lesion; According to RECIST 1.1 standard, it is suitable to evaluate the therapeutic response and progress of tumor.
  • 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 or male patients, and they agree to take effective contraceptive measures until 30 days after cells infusion.

Who cannot join

  • Patients with active viral or bacterial infection, and have failed to be controlled by anti-infective treatment.
  • Patients with seropositive response of Human immunodeficiency virus (HIV) and syphilis, or fail to control the hepatitis B virus or hepatitis C virus infection.
  • Patients who are undergoing treatment of autoimmune or organ transplantation diseases, or patients who need long-term use of immunosuppressive drugs such as glucocorticoid.
  • Patients with severe heart and lung dysfunction, high blood pressure and cannot be controlled with medicine, unstable coronary artery disease (uncontrolled arrhythmias, unstable angina pectoris), uncompensated congestive heart failure, myocardial infarction within six months.
  • Patients with any other illness 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.
  • Received cancer treatment prior to enroll the group within the following time (including drug clinical trials):
Show all 9Show fewer
  • The withdrawal time of chemotherapy before enrollment was shorter than the treatment cycle of chemotherapy.
  • The use of anti-tumor therapy within 4 weeks before the study or less than 5 times of the half-life period of the drugs (including radiation therapy, chemotherapy, small molecules and biological therapy or immunotherapy), the shortest period of time was as the criterion (but the shortest time should not be less than 21 days).
  • 7. Women patients in pregnancy period or suckling period.

Trial locations and contacts

1 site in 1 country.

Zhiwei Zhang, PhD contact

0086-021-59593168 ext. 8008

zhangzw@shcell.com

China1 site, 1 recruiting

  • China

    Shanghai, Shanghai Municipality, 200072

    Xue Yang, 0086-021-66301147, shsyiec@126.com

    Juemin Fang, 0086-021-39590256

    Recruiting

Other trials in China

About this study

Official title: A Clinical Study of PD-1 Antibody Expressing mesoCAR-T Cells for Patients With Mesothelin 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 target mesothelin and express PD-1 antibodies in adult patients with advanced recurrent or refractory malignant solid tumors, which were positive expression of mesothelin.

Read the detailed description

This study will be conducted using a phase I/II trial design to assess the safety and efficacy of the PD-1 antibody expressing mesoCAR-T for patients with mesothelin positive, advanced recurrent or refractory malignant solid tumors. MesoCAR-T can specifically and effectively kill the mesothelin positive cancer cells, PD-1 antibody 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, and then activated and engineered to express chimeric antigen receptors (CARs) targeting mesothelin and PD-1 antibody. Cells are proliferated in culture and returned to the patients by venous transfusion therapy. A total of 50 patients may be enrolled in the study. The total duration of the study is expected to be approximately 24 months.

Being tested
PD-1 antibody expressing mesoCAR-T cells
Keywords
mesothelin, PD-1, CAR T cells, solid tumor
Medical subject headings
Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

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

  • PD-1 antibody expressing mesoCAR-T cellsBiological

    Patients with mesothelin positive cancer will be infused the PD-1 antibody expressing mesoCAR-T cells. The modified mesoCAR-T cells can specifically kill mesothelin positive cancer cells and secrete PD-1 antibody, which could enhance the cytotoxicity of mesoCAR-T cells and activate the tumor infiltrating lymphocytes.

Study groups in NCT03615313
Study groupRoleWhat they receive
PD-1 antibody expressing mesoCAR-T cellsExperimentalPatients will receive two cycles of PD-1 antibody expressing mesoCAR-T cells treatment. Every cycle, peripheral blood mononuclear cells (PBMC) are collected on day -18, CAR-T cells are cultured in a GMP standard workshop. Patients are given a three-day regimen of chemotherapy consisting of fludarabine and cyclophosphamide aimed to deplete the lymphocytes before cells infusion. Then the patients will receive an i.v.gtt infusion of PD-1 antibody expressing mesoCAR-T cells from day 1 to day 3 (±3days).
Receives: Biological: PD-1 antibody expressing mesoCAR-T cells

What is being measured

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

  1. Incidence of treatment-related adverse events of infusion of autologous PD-1 antibody expressing mesothelin-targeted CAR-Tcells

    Incidence of treatment-related adverse events are assessed using the NCI CTCAE V4.0 criteria.

    Measured: 2 years

Secondary outcomes (3)

  1. Objective response rate (ORR) of the treatment using PD-1 antibody expressing mesoCAR-T cells for advanced solid tumors

    Objective response rate (ORR) of the treatment is assessed according to the response evaluation criteria in solid tumor version 1.1 (RECIST1.1), which contains complete response (CR) and partial response (PR).

    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 posted3 Aug 2018
  2. Study start6 Aug 2018 (estimated)
  3. Primary completion3 Aug 2020 (estimated)
  4. Study completion3 Dec 2020 (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
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03615313
Sponsor's protocol ID
SHSY-IEC-4.0/18-09/02
Acronym
PAEMCMPAST
Status last verified
Jul 2018
First submitted
28 Jun 2018
Last updated
3 Aug 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Fang J, Ding N, Guo X, Sun Y, Zhang Z, Xie B, Li Z, Wang H, Mao W, Lin Z, Qin F, Yuan M, Chu W, Qin H, Qian Q, Xu Q. alphaPD-1-mesoCAR-T cells partially inhibit the growth of advanced/refractory ovarian cancer in a patient along with daily apatinib. J Immunother Cancer. 2021 Feb;9(2):e001162. doi: 10.1136/jitc-2020-001162.

    PubMed 33589520

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing PD-1 antibody expressing mesoCAR-T cells 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 11 inclusion and 9 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 3 Aug 2018. 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, PhD (0086-021-59593168 ext. 8008, 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 of infusion of autologous PD-1 antibody expressing mesothelin-targeted CAR-Tcells (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 NCT03615313, 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 3 Aug 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in