Testing MLN0128 (TAK-228) as Potentially Targeted Treatment in Cancers With mTOR Genetic Changes (MATCH - Subprotocol L)

NCT06385496 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2024-01145EAY131-LU10CA180820
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II MATCH treatment trial tests how well MLN0128 (TAK-228) works in treating patients with cancer that has certain genetic changes called mTOR mutations. MLN0128 (TAK-228) may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Advanced Lymphoma; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Multiple Myeloma; Advanced Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. 90% two-sided confidence interval is calculated for ORR. For the purposes of this study, patients should be re-evaluated for response: * For treatments given in 21 day (3 week) cycles: every 3 cycles (9 weeks) for the first 33 cycles, and every 4 cycles thereafter (12 weeks) * For treatments given in 28 day (4 week) cycles: every 2 cycles (8 weeks) for the first 26 cycles, and every three cycles thereafter (12 weeks) * For treatments given in 42 day (6 week) cycles: every 2 cycles (12 weeks)

  Up to 3 years

Secondary Outcomes (3)

• Overall survival (OS)

  From start of treatment on that step until death, or censored at the date of last contact, assessed up to 3 years

• 6-month progression free survival (PFS)

  From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed at 6 months

• Progression free survival

  From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed up to 3 years

Study Arms (1)

Treatment (sapanisertib [MLN0128 (TAK-228)])

EXPERIMENTAL

Patients receive sapanisertib (MLN0128 \[TAK-228\]) PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo biopsies and blood sample collection on study.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Sapanisertib

Interventions

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (sapanisertib [MLN0128 (TAK-228)])

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (sapanisertib [MLN0128 (TAK-228)])

Computed Tomography PROCEDURE

Undergo CT scan

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

Treatment (sapanisertib [MLN0128 (TAK-228)])

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

Treatment (sapanisertib [MLN0128 (TAK-228)])

Sapanisertib DRUG

Given PO

Also known as: INK-128, INK128, MLN-0128, MLN0128, TAK-228

Treatment (sapanisertib [MLN0128 (TAK-228)])

Eligibility Criteria

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

You may qualify if:

• Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol
• Patients must fulfill all eligibility criteria of MATCH Master Protocol at the time of registration to treatment step (Step 1, 3, 5, 7)
• Patients must have a mutation in mTOR, KEAP1 or NFE2L2 as determined via the MATCH Master Protocol
• Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must NOT have any of the following cardiac criteria:
• Clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block, Corrected QT Interval \[QTc\] interval \> 480 milliseconds)
• Uncontrolled hypertension (i.e., systolic blood pressure \>180 mm Hg, diastolic blood pressure \> 95 mm Hg). Use of anti-hypertensive agents to control hypertension before cycle 1, day 1 is allowed
• Known pulmonary hypertension.
• Patients must not have known hypersensitivity to MLN0128 or compounds of similar chemical or biologic composition
• Patients must not have known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection, but may have had previously treated and successfully eradicated hepatitis C virus (HCV)
• Patients must have none of the following within six months of receiving the first dose of MLN0128 (TAK-228): ischemic, myocardial or cerebrovascular event, class III or IV heart failure, placement of pacemaker, or pulmonary embolism
• Patients must have no manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128 (TAK-228)
• Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met:
• Brain metastases which have been treated
• No evidence of disease progression for \>= 1 months before the first dose of study drug
• No hemorrhage after treatment

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, 19103, United States

Location

MeSH Terms

Conditions

Lymphoma; Multiple Myeloma

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; sapanisertib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

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

• John L Hays

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: April 26, 2024
• Study Start: March 12, 2017
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)