Targeting CD276 (B7-H3) Positive Solid Tumors by 4SCAR-276

NCT04432649 | Unknown Phase 1

• 1 other identifier: GIMI-IRB-20009
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

Patients with refractory and/or recurrent solid tumor have poor prognosis despite complex multimodel therapy and therefore, novel approaches are urgently needed. This study attempts to treat these diseases using T cells genetically modified with a 4th generation lentiviral chimeric antigen receptor (4SCAR fused with an inducible apoptotic caspase 9 domain) targeting CD276 (B7-H3). The 4SCAR-CD276-modified T cells (4SCAR-276) can recognize and kill tumor cells through the recognition of CD276, a surface protein expressed at high levels on many types of tumors but at low levels on normal tissues. This study will evaluate the side effects and effective doses of 4SCAR-276 in treating refractory and/or recurrent tumors.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Number of patients with adverse events

  Determine the toxicity profile the 4SCAR-276-modified T cells with Common Toxicity Criteria for Adverse Effects version 4.0

  3 years

Secondary Outcomes (2)

• Anti-tumor effects

  1 year

• Survival time of the patients

  3 years

Study Arms (1)

Effectiveness of 4SCAR-276 T cells

EXPERIMENTAL

The 4SCAR-276 T cells can recognize and kill tumor cells through the recognition of CD276 .This study will evaluate the side effects and effective doses of 4SCAR-276 T cells in treating refractory and recurrent solid tumors

Biological: 4SCAR-276

Interventions

4SCAR-276 BIOLOGICAL

The 4SCAR-276 T cells can recognize and kill tumor cells through the recognition of CD276 .This study will evaluate the side effects and effective doses of 4SCAR-276 T cells in treating refractory and recurrent solid tumors

Also known as: CD276-specific 4th Generation CART

Effectiveness of 4SCAR-276 T cells

Eligibility Criteria

• Age: 1 Year - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with tumors have received standard first-line therapy and have been judged to be non-resectable, metastatic, progressive or recurrent.
• The CD276 antigen status of the tumor is determined for eligibility. Positive expression is defined by antibody staining results based on immunohistochemistry or flow cytometry analysis.
• Body weight greater than or equal to 10 kg.
• Age: ≥1 year and ≤ 75 years of age at the time of enrollment.
• Life expectancy: at least 8 weeks.
• Prior Therapy: 1) There is no limit to the number of prior treatment regimens. Any grade 3 or 4 non-hematologic toxicity of any previous therapy must have resolved to grade 2 or less. 2) Must not have received hematopoietic growth factors for at least 1 week prior to mononuclear cells collection. 3) At least 7 days must have elapsed since the completion of therapy with a biologic agent, targeted agent, tyrosine kinase inhibitor or a metronomic nonmyelosuppressive regimen. 4) At least 4 weeks must have elapsed since prior therapy that included a monoclonal antibody. 5) At least 1 week since any radiation therapy at the time of study entry.
• Karnofsky/jansky score of 60% or greater.
• Cardiac function: Left ventricular ejection fraction greater than or equal to 40/55 percent .
• Pulse Ox greater than or equal to 90% on room air.
• Liver function: defined as alanine transaminase (ALT) \<3x upper limit of normal (ULN), aspartate aminotransferase (AST) \<3x ULN; serum bilirubin and alkaline phosphatase \<2x ULN.
• Renal function: Patients must have serum creatinine less than 3 times upper limit of normal.
• Marrow function: White blood cell count ≥1000/ul, Absolute neutrophil count ≥500/ul, Absolute lymphocyte count ≥500/ul, Platelet count ≥25,000/ul (not achieved by transfusion).
• Patients with known bone marrow metastatic disease will be eligible for study as long as they meet hematologic function criteria, and the marrow disease not evaluable to have hematologic toxicity.
• For all patients enrolled in this study, themselves or their parents or legal guardians must sign an informed consent and assent.

You may not qualify if:

• Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or major organ dysfunction, or grade 3 hematologic toxicity.
• Untreated central nervous system (CNS) metastasis: Patients with CNS tumor involvement that has been treated and/or is stable for at least 6 weeks following completion of therapy are eligible.
• Previous treatment with other genetically engineered CD276-CAR T cells or CD276 antibody therapy.
• Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.
• Patients who require systemic corticosteroid or other immunosuppressive therapy.
• Evidence of tumor potentially causing airway obstruction.
• Inability to comply with protocol requirements.
• Insufficient CAR T cells availability.

Sponsors & Collaborators

• Shenzhen Geno-Immune Medical Institute: lead
• Sun Yat-sen University: collaborator
• Shenzhen Children's Hospital: collaborator

Study Sites (3)

Shenzhen Children's Hospital

Shenzhen, Guangdong, 518000, China

RECRUITING

Shenzhen Geno-immune Medical Institute

Shenzhen, Guangdong, 518000, China

RECRUITING

Sun Yat-Sen University

Shenzhen, Guangdong, 518107, China

RECRUITING

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President

Study Record Dates

• First Submitted: June 8, 2020
• First Posted: June 16, 2020
• Study Start: June 1, 2020
• Primary Completion: May 31, 2023
• Study Completion: May 31, 2024
• Last Updated: June 16, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)