NCT05588453

Natural Killer Cell Therapy (UD TGFbetai NK Cells) and Temozolomide for the Treatment of Stage IV Melanoma Metastatic to the Brain

A Phase I/II Study of Ex-Vivo Expanded Allogeneic Universal Donor (UD) TGFbi NK Cell Infusions in Combination With Temozolomide as a Lymphodepleting Agent in Patients With Melanoma Metastatic to the Brain

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Kari Kendra · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial tests the safety, side effects, and best dose of universal donor UD TGFbetai natural killer (NK) cells, and whether UD TGFbetai NK cells with temozolomide works to shrink tumors in patients with stage IV melanoma that has spread to the brain (metastatic to the brain). NK cells are immune cells that contribute to anti-tumor immunity by recognizing and destroying transformed or stressed cells. Temozolomide is in a class of medications called alkylating agents. It works by slowing or stopping the growth of cancer cells in the body. Giving UD TGFbetai NK cell and temozolomide may work better in treating patients with stage IV melanoma.

Detailed description

PRIMARY OBJECTIVES: I. To confirm the safety and tolerability of UD TGFbetai NK cells in combination with temozolomide as a lymphodepleting agent in patients with melanoma metastatic to the brain and to determine the recommended phase 2 dose (RP2D). (Phase 1) II. To determine the intracranial response rate. (Phase 2) SECONDARY OBJECTIVES: I. To define the toxicities of UD TGFbetai NK cells when delivered with temozolomide as a lymphodepleting agent. (Phase 1) II. To define the pharmacokinetics (pK) associated with UD TGFbetai NK cells when used in combination with temozolomide as a lymphodepleting agent in patients with metastatic melanoma. (Phase 1) III. To determine the extracranial response rate. (Phase 2) IV. To determine progression free survival (PFS) (intracranial, extracranial, overall). (Phase 2) V. To assess overall survival (OS). (Phase 2) VI. To continue to assess the safety of temozolomide in combination with UD TGFbetai NK cells in a patient with melanoma metastatic to the brain. (Phase 2) EXPLORATORY/CORRELATIVE OBJECTIVES: I. To assess the phenotype and function of the UD TGFbetai NK cells and correlate with clinical outcomes. II. To assess in vivo persistence of UD TGFbetai NK cells after adoptive transfer and correlate with clinical outcomes. III. To assess immune status, inflammatory cytokine levels, and anti-melanoma cell activity. OUTLINE: This is a phase I, dose-escalation study of UD TGFbetai NK cells followed by a phase II study. Patients receive UD TGFbetai NK cells intravenously (IV) over 30 minutes on day 1 and temozolomide orally (PO) daily on days 1-5. Treatment with UD TGFbetai NK cells repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Cycles of temozolomide repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for up to 5 years.

Conditions

• Clinical Stage IV Cutaneous Melanoma AJCC v8
• Metastatic Malignant Neoplasm in the Brain
• Metastatic Melanoma
• Pathologic Stage IV Cutaneous Melanoma AJCC v8

Interventions

Type	Name	Description
BIOLOGICAL	Natural Killer Cell Therapy	Given UD TGFbi NK cell IV
DRUG	Temozolomide	Given PO

Timeline

• Start date: 2023-03-01
• Primary completion: 2026-04-15
• Completion: 2026-04-15
• First posted: 2022-10-20
• Last updated: 2026-01-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study