DAY101 In Gliomas and Other Tumors

NCT03429803 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: 17-589P50CA165962PNOC014
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 15

Brief Summary

This research study is studying a drug Tovorafenib/DAY101 (formerly TAK-580, MLN2480) as a possible treatment a low-grade glioma that has not responded to other treatments. The name of the study drug involved in this study is: • Tovorafenib/DAY101 (formerly TAK-580, MLN2480)

Conditions

Low-grade Glioma

Keywords

low-grade glioma

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT)

  A DLT is defined as an AE assessed as at least possibly related to the study medication, which occurs during Cycle 1 (typically 28 days following the first dose of DAY101)

  Greater and equal 28 days

Secondary Outcomes (4)

• Blood samples for DAY101 concentration measurements (i.e. pharmacokinetic measures)

  cycle 1 day 1 1-4 hours post dose; cycle 1 day 3-6 random level; cycle 2 day 1 pre-dose; cycle 3 day 1 random level; end of therapy or at time of toxicity requiring patient be taken off study or dose held; time of surgery if applicable)

• Best Overall Response

  48 Weeks

• Number of participants with adverse events

  48 Weeks

• Number of participants with serious adverse events

  48 weeks

Study Arms (2)

DAY101 (formerly TAK-580, MLN2480) BSA </= 1.5m^2

EXPERIMENTAL

Phase I Part B BSA \</= 1.5m\^2 * Patients (\< 25 years) with radiographically recurrent or radiographically progressive non-hematologic malignancies (Central Nervous System (CNS) or solid tumors) associated with activation of the RAS/RAF/MEK/ERK pathway will be eligible with the exception of patients with NF1 * Study treatment cycle lasts 28 days, oral, once a week

Drug: DAY101

DAY101 (formerly TAK-580, MLN2480) BSA > 1.5m^2

EXPERIMENTAL

Phase I Part B BSA \> 1.5m\^2 * Patients (\< 25 years) with radiographically recurrent or radiographically progressive non-hematologic malignancies (Central Nervous System (CNS) or solid tumors) associated with activation of the RAS/RAF/MEK/ERK pathway will be eligible with the exception of patients with NF1 * Study treatment cycle lasts 28 days, oral, once a week

Drug: DAY101

Interventions

DAY101 DRUG

28 day cycle, oral, once per week

Also known as: MLN2480, TAK-580

DAY101 (formerly TAK-580, MLN2480) BSA </= 1.5m^2; DAY101 (formerly TAK-580, MLN2480) BSA > 1.5m^2

Eligibility Criteria

• Age: 1 Year - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants must meet the following criteria on screening examination to be eligible to participate in the study:
• Phase I
• Pediatric patients with radiographically recurrent or radiographically progressive non-hematologic malignancies (Central Nervous System (CNS) or solid tumors) associated with activation of the RAS/RAF/MEK/ERK pathway will be eligible with the exception of patients with NF1.
• Mutational status requires a pathology report, genomic sequencing, or immunohistochemical report of a mutation or activation of the RAS/RAF/MEK/ERK pathway.
• The remaining criteria include:
• Patients must be \>1 year and \<25 years old.
• Patients must have adequate performance status:
• Karnofsky ≥ 50 for patients ≥ 16 years of age (See Appendix A).
• Lansky ≥ 50 for patients \< 16 years of age (See Appendix A).
• Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score (See Appendix A).
• A patient who has failed standard therapy. Note: standard of care for resectable low grade glioma, as an example, is surgery. Therefore, patients with low grade glioma that recurs after presumed gross total resection may enroll without prior chemotherapy exposure.
• At least 1 measurable lesion that can be reproducibly measured in 2 dimensions
• Previous chemotherapy and hormone therapy (excluding physiologic replacement) must be completed at least 4 weeks or 4 half-lives, whichever is longer, prior to administration of DAY101.
• Previous immunotherapy/ monoclonal antibody use must be completed at least 4 weeks or 4 half lives, whichever is longer prior to administration of DAY101.
• Previous MEK or BRAF inhibitors must be completed at least 7 days prior to the administration of DAY101.

You may not qualify if:

• Patients with clinical progression but without radiographically recurrent or radiographically progressive disease.
• Patients with NF1
• History of any major disease that might interfere with safe protocol participation, as determined by the investigator
• Patients with a history or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO), or ophthalmopathy present at baseline that would be considered a risk factor for CSR or RVO
• \--- Patients with history of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) or Steven Johnson Syndrome in the setting of prior MEK or BRAF inhibitor exposure
• Laboratory values:
• Absolute neutrophil count (ANC) ≤ 1000/μL
• Platelet count ≤ 75,000/μL (transfusion independent)
• Hemoglobin \< 9 g/dL (hemoglobin may be supported by transfusion, erythropoietin, or other approved hematopoietic growth factors)
• Serum bilirubin ≥ 1.5 × upper limit of normal (ULN) or ³ 2 ´ ULN if patient is known to have Gilbert's Disease as the only underlying hepatic disorder
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 2.5 × ULN. AST and ALT ≥ 5 × ULN for patients with liver metastasis
• Serum creatinine ≥ 2.0 mg/dL
• Current enrollment in any other investigational treatment study
• Evidence of current uncontrolled cardiovascular conditions, including but not limited to clinically significant cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction, within the past 6 months
• Active hepatitis or human immunodeficiency virus infection

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Pacific Pediatric Neuro-Oncology Consortium: collaborator
• Team Jack Foundation: collaborator
• Day One Biopharmaceuticals, Inc.: collaborator
• Karen D. Wright, MD: lead
• PLGA Fund at Pediatric Brain Tumor Foundation: collaborator

Study Sites (15)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of California, San Diego

San Diego, California, 92123, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massacusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institite

Boston, Massachusetts, 02215, United States

Location

Children's Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Utah

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Interventions

tovorafenib

Study Officials

• Karen D. Wright, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: February 12, 2018
• Study Start: February 27, 2018
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (15)