NCT05677373

Testing the Safety and Effectiveness of Combining Two Drugs, PLX2853 and Trametinib in the Treatment of Advanced Uveal Melanoma

Phase I/II Study of BET and MEK Inhibition in Advanced Uveal Melanoma

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Alliance for Clinical Trials in Oncology · 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 PLX2853 in combination with trametinib in treating patients with uveal (eye) melanoma that has spread to other places in the body (metastatic) or nearby tissues or lymph nodes (locally advanced), or that cannot be removed by surgery (unresectable). PLX2853 works by targeting and inhibiting certain activities within cells that promote tumor growth. By inhibiting these activities, PLX2853 may help to stabilize or reduce the growth of tumor cells. Trametinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps stop the spread of tumor cells. Giving PLX2853 in combination with trametinib may help to shrink and stabilize tumor cells in patients with advanced uveal melanoma.

Detailed description

CO-PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose(s) (MTD(s)) and recommended phase II dose. (Phase I) II. To evaluate whether combination BRD4 inhibitor PLX2853 (PLX2853) and trametinib demonstrate clinical activity in advanced uveal melanoma (UM), as determined by a best response rate of 25% compared to a historical rate of 10%. (Phase II) SECONDARY OBJECTIVES: I. To evaluate the overall response rate (ORR) associated with combination PLX2853 and trametinib. II. To evaluate the progression-free survival (PFS) associated with combination PLX2853 and trametinib. III. To evaluate the overall survival (OS) associated with combination PLX2853 and trametinib. IV. To characterize the adverse event profile associated with combination PLX2853 and trametinib. PHARMACOKINETICS SECONDARY OBJECTIVE: I. To evaluate the pharmacokinetic profile of combination PLX2853 and trametinib. OUTLINE: This is a phase I dose-escalation study of PLX2853 and trametinib followed by a phase II study. Patients receive PLX2853 orally (PO) in combination with trametinib PO throughout the study. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) with contrast and collection of blood at screening and on study.

Conditions

• Advanced Uveal Melanoma
• Metastatic Uveal Melanoma
• Unresectable Uveal Melanoma

Interventions

Type	Name	Description
DRUG	BRD4 Inhibitor PLX2853	Given PO
DRUG	Trametinib	Given PO
PROCEDURE	Computed Tomography	Undergo CT with contrast
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI with contrast
PROCEDURE	Biospecimen collection	Undergo collection of blood
PROCEDURE	Biospecimen collection	Correlative studies

Timeline

• Start date: 2023-01-13
• Primary completion: 2025-07-31
• Completion: 2025-07-31
• First posted: 2023-01-10
• Last updated: 2023-08-18

Regulatory

• FDA-regulated drug study