NCT06223542

Studying TAK-243 in Patients With Advanced Cancer

A Phase I Study to Investigate the Safety of the Ubiquitin Activating Enzyme Inhibitor TAK-243 in Adult Solid Tumor and Lymphoma Patients

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 95 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of ubiquitin-activating enzyme (UAE) inhibitor TAK-243 (TAK-243) in treating patients with a solid tumor that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic) and in patients with lymphoma. TAK-243 is a drug that binds to and inhibits the ubiquitin-activating enzyme, an enzyme that is more active on cancer cells than healthy cells, inhibiting tumor cell proliferation and survival.

Detailed description

PRIMARY OBJECTIVE: I. To establish the safety, tolerability, and the recommended phase II dose of UAE inhibitor TAK-243 (TAK-243) administered twice-weekly or once-weekly in patients with advanced solid tumors and lymphomas. SECONDARY OBJECTIVES: I. To evaluate the pharmacokinetic (PK) profiles of TAK-243 administered on twice-weekly and once-weekly schedules in patients with advanced solid tumors and lymphomas. II. To determine the effects of TAK-243 on levels of K48-linked ubiquitination in pre- and post-treatment tumor biopsies. III. To observe and record anti-tumor activity. EXPLORATORY OBJECTIVES: I. To determine the effects of TAK-243 on the endoplasmic reticulum (ER) stress marker CHOP, Mcl-1-Noxa heterodimer formation, and the apoptosis marker cleaved caspase-3 in pre- and post-treatment tumor biopsies II. To evaluate potential associations between TAK-243 activity and tumor genomic alterations or ribonucleic acid (RNA) expression profiles. III. To preliminarily assess progression-free survival (PFS) and overall survival (OS) for TAK-243 monotherapy in patients with advanced solid tumors and lymphomas. OUTLINE: This is a dose-escalation study of TAK-243 followed by a dose-expansion study. Patients are assigned to 1 of 2 arms. ARM A: Patients receive UAE inhibitor TAK-243 intravenously (IV) on days 1, 4, 8, and 11 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy on study, and undergo computed tomography (CT), magnetic resonance imaging (MRI), and collection of blood throughout the study, and may undergo echocardiograms (ECHO) as clinically indicated on study. ARM B: Patients receive UAE inhibitor TAK-243 IV once weekly (QW) on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy on study, and undergo CT, MRI, and collection of blood throughout the study, and may undergo ECHO as clinically indicated on study. After completion of study treatment, patients are followed up for 30 days.

Conditions

• Advanced Lymphoma
• Advanced Malignant Solid Neoplasm
• Indolent Non-Hodgkin Lymphoma
• Metastatic Malignant Solid Neoplasm
• Recurrent Malignant Solid Neoplasm
• Refractory Malignant Solid Neoplasm

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo collection of blood
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Echocardiography Test	Undergo ECHO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
DRUG	UAE Inhibitor TAK-243	Given IV

Timeline

• Start date: 2025-03-24
• Primary completion: 2027-04-15
• Completion: 2027-04-15
• First posted: 2024-01-25
• Last updated: 2026-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study