Clinical Study of CD276 Targeted Autologous Chimeric Antigen Receptor T Cell Infusion in Patients With CD276 Positive Advanced Solid Tumor

Cd276 (B7-H3) is an ideal target for car-t treatment because of its high expression on the surface of neuroblastoma, osteosarcoma, gastric cancer and lung cancer cells, but not in normal peripheral cells or tissues. In conclusion, car-t cell therapy has achieved exciting results in blood tumors, but it has been stopped in solid tumor. The main reason for the poor effect is the existence of tumor microenvironment of solid tumor, which inhibits the chemotaxis and infiltration of car-t cells to tumor site. Therefore, in this clinical experiment, we will explore the best model of car-t therapy for solid tumor by intravenous and local tumor injection, which will bring new hope to patients with osteosarcoma, neuroblastoma and gastric cancer

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Cancer; Lung Cancer; Osteosarcoma; Neuroblastoma
• Intervention / Treatment: Drug: Targeting CD276 CAR T cells

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yi Zhang, Doctor; Phone Number: +8615138928971; Email: 1248135168@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patients were aged from 1 to 70 years old (including the cut-off value), and the gender was not limited;
• The expected survival time was more than 12 weeks;
• ECoG score was 0-2;
• One of the following tumor types was confirmed by pathology: osteosarcoma, neuroblastoma, gastric cancer or lung cancer, and the positive rate of cd276 expression in tumor tissue was more than 50% by immunohistochemistry;
• Patients with ineffective standard treatment methods (such as postoperative recurrence, chemotherapy, radiotherapy, and progression after targeted drugs);
• According to RECIST 1.1, there was at least one measurable lesion (the longest diameter of solid lesion ≥ 10 mm, or the short diameter of lymph node lesion ≥ 15 mm);
• The function of main organs was normal (white blood cell count ≥ 3 × 109 / L, neutrophil count ≥ 1.5 × 109 / L, hemoglobin ≥ 8.5g/dl, platelet count ≥ 80 × 109 / L and lymphocyte count at 1 × 109 / L (including) ~ 4 × 109 / L (inclusive);

• The liver and kidney function and cardiopulmonary function meet the following requirements:

  1. Urea and serum creatinine ≤ 1.5 × ULN；
  2. Left ventricular ejection fraction ≥ 50%;
  3. Baseline oxygen saturation ≥ 94%;
  4. Total bilirubin ≤ 1.5 × ULN； ALT and AST ≤ 2.5 × ULN；
• The patient or legal representative can fully understand the significance and risk of this trial and has signed the informed consent.

Exclusion Criteria:

• Patients with history of immune deficiency or autoimmune diseases (including but not limited to rheumatoid arthritis, systemic lupus erythematosus, vasculitis, multiple sclerosis, insulin-dependent diabetes, etc.); Patients with graft-versus-host disease (GVHD) or need immunosuppressive agents;
• There was a history of other second malignancies in 5 years before screening;
• Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) were positive, and the peripheral blood HBV DNA titer was not within the normal reference value; HCV antibody and HCV RNA in peripheral blood were positive; HIV antibody positive patients; Syphilis was positive;
• Severe heart disease: including but not limited to unstable angina pectoris, myocardial infarction (within 6 months before screening), congestive heart failure (NYHA classification ≥ III), severe arrhythmia;
• Unstable systemic diseases judged by researchers: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment;
• Within 7 days before screening, there were active or uncontrollable infections requiring systemic treatment (except mild urogenital infection and upper respiratory tract infection);
• Pregnant or lactating women, female subjects who plan to conceive within one year after cell transfusion, or male subjects whose partners plan to conceive within one year after cell transfusion;
• Patients who had received car-t therapy or other gene modified cell therapy before screening;
• The subjects who were receiving systemic steroid treatment within 7 days before the screening or who needed long-term systemic steroid treatment (except inhalation or local use) were determined by the researchers;
• The ascites increased gradually after 2 weeks of conservative treatment (such as diuresis, sodium restriction, excluding ascites drainage);
• According to the judgment of the researcher, it does not conform to the situation of cell preparation;
• Other researchers think that it is not suitable for inclusion.

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
Other: T cell injection targeting CD276 chimeric antigen receptor	Drug: Targeting CD276 CAR T cells; Targeting CD276 autologous chimeric antigen receptor T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE	adverse event	2 years after treatment
ORR	Objective remission rate	12 weeks after treatment
Cmax	The highest concentration of CAR-T cells in peripheral blood after infusion	2 years after treatment

Collaborators and Investigators

• Sponsor: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
• Collaborators: The First Affiliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Anticipated): May 14, 2021
• Primary Completion (Anticipated): May 14, 2022
• Study Completion (Anticipated): May 14, 2023

Study Registration Dates

• First Submitted: April 25, 2021
• First Submitted That Met QC Criteria: April 25, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Actual): May 6, 2021
• Last Update Submitted That Met QC Criteria: April 30, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Osteosarcoma; Neuroblastoma
• Other Study ID Numbers: PA-P276-001

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No