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

NCT03615313 | Unknown Phase 1

• 1 other identifier: SHSY-IEC-4.0/18-09/02
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Solid Tumor

Keywords

mesothelin, PD-1, CAR T cells, solid tumor

Outcome Measures

Primary Outcomes (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.

  2 years

Secondary Outcomes (3)

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

  2 years

• Progression free survival

  2 years

• Overall survival

  2 years

Other Outcomes (2)

• Proliferation and persistence of mesothelin specific CAR-T cells in peripheral blood of the patients

  6 months

• PD-1 antibody level in peripheral blood of the patients after treatment

  6 months

Study Arms (1)

PD-1 antibody expressing mesoCAR-T cells

EXPERIMENTAL

Patients 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).

Biological: PD-1 antibody expressing mesoCAR-T cells

Interventions

PD-1 antibody expressing mesoCAR-T cells BIOLOGICAL

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.

PD-1 antibody expressing mesoCAR-T cells

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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):
• (1) The withdrawal time of chemotherapy before enrollment was shorter than the treatment cycle of chemotherapy.
• (2) 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).
• \. Women patients in pregnancy period or suckling period.

Sponsors & Collaborators

• Shanghai Cell Therapy Research Institute: lead

Study Sites (1)

China

Shanghai, Shanghai Municipality, 200072, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 33589520 DERIVED

MeSH Terms

Conditions

Parkinson Disease 4, Autosomal Dominant Lewy Body

Study Officials

• Qijun Qian, PhD

  Shanghai Cell Therapy Research Institute

  STUDY CHAIR

• Huajun Jin, PhD

  Shanghai Cell Therapy Research Institute

  STUDY CHAIR

• Qing Xu, PhD

  Shanghai 10th People's Hospital

  PRINCIPAL INVESTIGATOR

• Zhiwei Zhang, PhD

  Shanghai Cell Therapy Research Institute

  STUDY DIRECTOR

• Yan Sun

  Shanghai Cell Therapy Research Institute

  STUDY DIRECTOR

• Huimei Li, PhD

  Shanghai Cell Therapy Research Institute

  STUDY DIRECTOR

• Juemin Fang, PhD

  Shanghai 10th People's Hospital

  PRINCIPAL INVESTIGATOR

• Song Gao, PhD

  Shanghai 10th People's Hospital

  PRINCIPAL INVESTIGATOR

• Xianling Guo

  Shanghai 10th People's Hospital

  PRINCIPAL INVESTIGATOR

• Hui Wang

  Shanghai 10th People's Hospital

  PRINCIPAL INVESTIGATOR

• Zhongzheng Zhu

  Shanghai 10th People's Hospital

  PRINCIPAL INVESTIGATOR

• Jianhua Chen

  Shanghai 10th People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhiwei Zhang, PhD

CONTACT

0086-021-59593168; zhangzw@shcell.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2018
• First Posted: August 3, 2018
• Study Start: August 6, 2018
• Primary Completion: August 3, 2020
• Study Completion: December 3, 2020
• Last Updated: August 3, 2018

Record last verified: 2018-07

Locations

CN (1)