Bi-specific CAR-T cell therapy for solid tumors

GD2/PSMA Bi-specific CAR-T Cells For the Treatment of GD2 and PSMA Positive Solid Tumors

This study is testing a new treatment that uses modified immune cells to see if it can help people with hard-to-treat solid tumors fight their cancer better.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 1 Year to 75 Years
• Sex: All
• Sponsor: Shenzhen Geno-Immune Medical Institute (Academic / other)
• Drugs / interventions: CAR T, radiation, CAR-T, chimeric antigen receptor, immunotherapy
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT05437315 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of a novel bi-specific CAR-T cell therapy targeting GD2 and PSMA antigens in patients with refractory or recurrent solid tumors. The therapy involves genetically modifying T cells from patients to express a chimeric antigen receptor that enables them to recognize and attack tumor cells expressing these antigens. The study aims to assess how well these modified T cells persist and function in the body. By focusing on solid tumors, which have limited treatment options, this approach seeks to provide a new avenue for effective cancer therapy.

Who should consider this trial

Good fit: Ideal candidates include patients aged 1 to 75 with GD2 or PSMA positive solid tumors that are non-resectable, metastatic, or recurrent after standard therapies.

Not a fit: Patients with tumors that do not express GD2 or PSMA antigens or those with a life expectancy of less than 8 weeks may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could offer a new treatment option for patients with difficult-to-treat solid tumors.

How similar studies have performed: While CAR-T therapies have shown promise in hematological malignancies, this bi-specific approach in solid tumors is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Patients with tumors have received standard first-line therapy and have been judged to be non-resectable, metastatic, progressive or recurrent.
2. The expression status of GD2 or PSMA antigens in the tumor tissue will be determined for eligibility. Positive expression is defined by GD2 and PMSA antibody staining results based on immunohistochemistry or flow cytometry analyses.
3. Body weight greater than or equal to 10 kg.
4. Age: ≥1 year and ≤ 75 years of age at the time of enrollment.
5. Life expectancy: at least 8 weeks.
6. Prior Therapy:

   There is no limit to the number of prior treatment regimens. Any grade 3 or 4 non-hematologic toxicity of any previous therapy must be resolved to grade 2 or less.
7. Participant must not have received hematopoietic growth factors for at least 1 week prior to mononuclear cells collection.
8. At least 7 days must have elapsed since the completion of therapy with a biologic agent, selected targeted agent or a metronomic non-myelosuppressive regimen.
9. At least 4 weeks must have elapsed since prior therapy that included a monoclonal antibody.
10. At least 1 week since any radiation therapy at the time of study entry.
11. Karnofsky/jansky score of 60% or greater.
12. Cardiac function: Left ventricular ejection fraction greater than or equal to 40/55 percent.
13. Pulse Ox greater than or equal to 90% on room air.
14. 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.
15. Renal function: Patients must have serum creatinine less than 3 times upper limit of normal.
16. 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).
17. Patients with known bone marrow metastatic disease will be eligible for study as long as they meet hematologic function criteria, and the marrow disease does not have hematologic toxicity.
18. For all patients enrolled in this study, themselves or their parents or legal guardians must sign an informed consent and assent.

Exclusion Criteria:

1. Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or major organ dysfunction, or greater than grade 2 hematologic toxicity.
2. Untreatable 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.
3. Previous treatment with other genetically engineered GD2 or PSMA-specific CAR T cells or antibody therapy.
4. Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.
5. Patients who require systemic corticosteroid or other immunosuppressive therapy.
6. Evidence of tumor potentially causing airway obstruction.
7. Inability to comply with protocol requirements.
8. Insufficient CAR T cells availability.

Where this trial is running

Shenzhen, Guangdong

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

Study contacts

• Study coordinator: Lung-Ji Chang, PhD

Conditions Solid Tumor; CAR-T; Solid tumor; GD2; PSMA