CAR-T therapy targeting NG2 and DLL3 for melanoma

Safety and Efficacy of NG2 and DLL3 CAR-T Therapy Targeting Melanoma

This will test a CAR-T cell therapy that targets NG2 and DLL3 in adults with relapsed or refractory metastatic melanoma whose tumors express those antigens.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shenzhen Geno-Immune Medical Institute (other)
• Drugs / interventions: CAR T, CART, radiation, CAR-T, chemotherapy, immunotherapy
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT07193966 on ClinicalTrials.gov

What this trial studies

This phase 1/2 interventional trial uses autologous CAR-T cells engineered to recognize two surface proteins, NG2 and DLL3, to treat patients with non-resectable, metastatic, progressive, or recurrent melanoma. Eligible tumors must be positive for NG2 and DLL3 by immunohistochemistry or flow cytometry, and participants must meet age and weight criteria and have sufficient life expectancy. The protocol includes collection of the patient’s mononuclear cells, manufacturing of dual-targeting CAR-T products, and monitored infusion with safety and efficacy follow-up. The trial is conducted at Shenzhen Geno-Immune Medical Institute and aims to characterize feasibility, safety, and clinical activity.

Who should consider this trial

Good fit: Adults aged 18–75 years, weighing at least 40 kg, with non-resectable, metastatic or recurrent melanoma that tests positive for NG2 and DLL3 and who have completed prior standard therapies are the intended candidates.

Not a fit: Patients whose tumors do not express NG2 and DLL3, who are medically unfit for leukapheresis or cell therapy, or who have very limited life expectancy are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, the therapy could shrink tumors or slow disease progression in patients whose melanoma no longer responds to standard treatments.

How similar studies have performed: CAR-T therapies have shown strong success in blood cancers but have had limited and mixed results in solid tumors, and dual-targeting CAR-T approaches like NG2/DLL3 remain experimental with limited clinical data.

Eligibility criteria

Inclusion Criteria:

* Patients with tumors have received standard first-line therapy and have been diagnosed with non-resectable, metastatic, progressive or recurrent conditions.
* The expression status of NG2 and DLL3 antigens of the tumor has been determined for eligibility. Positive expression is defined by NG2 and DLL3 antibody staining results based on immunohistochemistry or flow cytometry analyses.
* Body weight greater than or equal to 40 kg.
* Age: ≥18 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. Participants 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 any biologic agent, targeted agent, tyrosine kinase inhibitor or metronomic non-myelosuppressive regimen.
  4. At least 4 weeks must have elapsed since prior therapy that includes a monoclonal antibody.
  5. At least 1 week must has elapsed since any radiation therapy at the time of study entry.
* Karnofsky/jansky score of 70% 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 ULN.
* 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 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 availability of CART cells.

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: Melanoma, melanoma, CAR-T, chimeric antigen receptor, adoptive T cell transfer, NG2, DLL3