Studying TAK-243 in Patients With Advanced Cancer

NCT06223542 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: NCI-2022-1119410299
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD)

  The MTD for each arm will be based on the assessment of dose-limiting toxicities (DLTs) and will be defined as the dose level at which less than one-third of patients (\< 2/6 patients) treated at that dose experience a DLT, with the next higher dose level demonstrating a one-third or greater number of patients (\>= 2/3 or \>= 2/6 patients) having DLT.

  Within the first cycle of treatment (Arm A: 21-day cycle; Arm B: 28-day cycle)

• Recommended phase 2 dose

  Within the first cycle of treatment (Arm A: 21-day cycle; Arm B: 28-day cycle)

• Incidence of DLTs

  A DLT is defined as an adverse event that is felt to be related (possibly, probably, or definitely) to administration of study drugs, and meets pre-specified criteria. All toxicities will be reported for all patients who receive any amount of study drug on this study.

  Within the first cycle of treatment (Arm A: 21-day cycle; Arm B: 28-day cycle)

Secondary Outcomes (2)

• Pharmacodynamic (PD) variables

  Up to 30 days after the last dose of treatment

• Objective tumor response

  Up to 30 days after the last dose of treatment

Other Outcomes (2)

• Progression-free survival

  Up to 30 days after the last dose of treatment

• Overall survival

  Up to 30 days after the last dose of treatment

Study Arms (2)

Arm A (twice weekly UAE inhibitor TAK-243)

EXPERIMENTAL

Patients receive UAE inhibitor TAK-243 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 CT, MRI, and collection of blood throughout the study, and may undergo ECHO as clinically indicated on study.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Drug: UAE Inhibitor TAK-243

Arm B (once weekly UAE inhibitor TAK-243)

EXPERIMENTAL

Patients receive UAE inhibitor TAK-243 IV 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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Drug: UAE Inhibitor TAK-243

Interventions

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Arm A (twice weekly UAE inhibitor TAK-243); Arm B (once weekly UAE inhibitor TAK-243)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm A (twice weekly UAE inhibitor TAK-243); Arm B (once weekly UAE inhibitor TAK-243)

UAE Inhibitor TAK-243 DRUG

Given IV

Also known as: AOB87172, MLN7243, TAK-243

Arm A (twice weekly UAE inhibitor TAK-243); Arm B (once weekly UAE inhibitor TAK-243)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Arm A (twice weekly UAE inhibitor TAK-243); Arm B (once weekly UAE inhibitor TAK-243)

Biospecimen Collection PROCEDURE

Undergo collection of blood

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm A (twice weekly UAE inhibitor TAK-243); Arm B (once weekly UAE inhibitor TAK-243)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm A (twice weekly UAE inhibitor TAK-243); Arm B (once weekly UAE inhibitor TAK-243)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically documented advanced or metastatic solid tumors with relapsed or refractory disease who have received standard-of-care or approved therapies known to confer clinical benefit, or patients with aggressive lymphomas who have received ≥ 2 prior lines of lymphoma-directed therapy and who do not have remaining effective treatment options (including transplant). Additionally, patients with indolent lymphomas must meet criteria for treatment.
• Patients must have measurable or evaluable disease
• Age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Hemoglobin \>= 9 g/dL (patients may be transfused to achieve this value; elevated indirect bilirubin due to post-transfusion hemolysis is allowed)
• Absolute neutrophil count \>= 1,000/mcL
• Platelets \>= 75,000/mcL
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 x institutional ULN OR =\< 5 x institutional upper limit of normal for patients with liver metastases at baseline
• Creatinine =\< 1.5 x institutional ULN OR creatinine clearance \>= 60 mL/min/1.73 m\^2 by Cockcroft-Gault
• Any prior therapy must have been completed \>= 4 weeks, or \>= 5 half-lives of the prior agent (whichever is shorter) prior to enrollment on protocol. Prior definitive radiation should have been completed \>= 4 weeks prior to enrollment; prior palliative radiation should have been completed \>= 2 weeks prior to enrollment. Patients must be \>= 2 weeks since any investigational agent administered as part of a Phase 0 study (where a sub-therapeutic dose of drug is administered) and should have recovered to grade 1 or baseline from any toxicities
• Female patients who:
• Are postmenopausal (age-related amenorrhea \>= 12 consecutive months or follicle-stimulating hormone \> 40 mIU/mL), for at least 1 year before the screening visit, OR
• Are surgically sterile (i.e., who had undergone hysterectomy or bilateral oophorectomy), OR
• If they are of childbearing potential:

You may not qualify if:

• Patients who are receiving any other investigational agents
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
• Life-threatening illness unrelated to cancer
• Patients with uncontrolled coagulopathy or bleeding disorder
• Known hepatic cirrhosis or severe pre-existing hepatic impairment
• Known cardiopulmonary disease defined as:
• Unstable angina pectoris;
• Congestive heart failure (New York Heart Association \[NYHA\] class III or IV);
• Myocardial infarction (MI) within 6 months prior to first dose (patients who had ischemic heart disease such as a \[acute coronary syndrome (ACS)\], MI, and/or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll);
• Cardiomyopathy
• Clinically significant arrhythmia:
• History of polymorphic ventricular fibrillation or torsade de pointes,
• Permanent atrial fibrillation (a fib), defined as continuous a fib for \>= 6 months,
• Persistent a fib, defined as sustained a fib lasting \> 7 days and/or requiring cardioversion in the 4 weeks before screening,
• Grade 3 a fib defined as symptomatic and incompletely controlled medically, or controlled with device (e.g., pacemaker) or ablation, and

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, 20892, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; TAK-243

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Sarah Shin, MD

  National Cancer Institute LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2024
• First Posted: January 25, 2024
• Study Start: March 24, 2025
• Primary Completion (Estimated): April 15, 2027
• Study Completion (Estimated): April 15, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)