4SCAR-GD2 therapy for GD2-positive solid tumors

Multicenter Trial of Phase I/II Studies on GD2 Positive Solid Tumors by 4SCAR-GD2

This will test whether a patient's own T cells, engineered with a 4SCAR-GD2 CAR, can treat people aged 1–65 with GD2-positive refractory or recurrent solid tumors.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 1 Year to 65 Years
• Sex: All
• Sponsor: Shenzhen Geno-Immune Medical Institute (other)
• Drugs / interventions: CAR T, radiation, chimeric antigen receptor, chemotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT02992210 on ClinicalTrials.gov

What this trial studies

Researchers will collect a patient's T cells by apheresis, genetically modify them with a fourth-generation lentiviral CAR that targets GD2 and includes an inducible caspase-9 safety switch, and expand the cells for infusion. Before infusion, patients receive a short preparative regimen of cyclophosphamide and fludarabine to help the modified T cells engraft. The trial uses dose-escalation (phase 1/2) to identify tolerable and potentially effective doses while monitoring for side effects, CAR T cell persistence, and tumor responses. Eligible participants must have GD2-positive, refractory or recurrent non-resectable/metastatic solid tumors and meet specified age, weight, and prior-therapy washout criteria.

Who should consider this trial

Good fit: Ideal candidates are people aged 1–65, weighing at least 10 kg, with GD2-positive refractory or recurrent non-resectable or metastatic solid tumors, life expectancy ≥8 weeks, and who meet prior-therapy washout and organ-function criteria.

Not a fit: Patients whose tumors do not express GD2, who cannot tolerate conditioning chemotherapy, or who have severe organ dysfunction are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, this therapy could shrink GD2-positive tumors and extend survival for patients with otherwise treatment-refractory solid cancers.

How similar studies have performed: Anti-GD2 CAR-T approaches have shown promise in pediatric neuroblastoma and in preclinical solid tumor models, but consistent, durable success in adult solid tumors has been limited to date.

Eligibility criteria

Inclusion Criteria:

* Patients with tumors have received standard first-line therapy and been judged to be non-resectable，metastatic,progressive or recurrent.
* The GD2 antigen status of the tumor will be determined for eligibility.Positive expression is defined by GD2 antibody staining results based on immunohistochemistry or flow cytometry analyses.
* Body weight greater than or equal to 10 kg.
* Age: ≥1 year and ≤ 65 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 weeks 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 for hematologic toxicity.
* For all patients enrolled in this study, their parents or legal guardians must sign an informed consent and assent.

Exclusion Criteria:

* Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or major organ dysfunction, with the exception of grade 3 hematologic toxicity.
* Untreated central nervous system (CNS) metastasis: Patients with previous CNS tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are eligible.
* Previous treatment with other genetically engineered GD2-CAR T cells.
* 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.

Where this trial is running

Shenzhen, Guangdong

• Shenzhen Geno-immune Medical Institute — Shenzhen, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Lung-Ji Chang — Shenzhen Geno-Immune Medical Institute
• Study coordinator: Lung-Ji Chang, PhD.

Conditions: Solid Tumor, CAR, chimeric antigen receptor, adoptive T cell transfer