Expanded Access Program (EAP) for Tovorafenib (DAY101) in RAF-Altered, Relapsed or Refractory Low-Grade Glioma

NCT05760586 | Unknown

• 1 other identifier: DAY101-EAP
• Study Type: expanded_access
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The DAY101-EAP is a multicenter, open-label, expanded access treatment protocol designed to provide access to tovorafenib (DAY101) for eligible patients.

Conditions

Low-grade Glioma

Keywords

DAY101; Toverafenib; Glioma; BRAF Mutation; RAF Alteration; Type II BRAF Inhibitor; Neoplasms

Interventions

Tovorafenib DRUG

Oral RAF inhibitor provided as an immediate-release tablet (100 mg) or powder for reconstitution (25 mg/mL)

Also known as: DAY101

Eligibility Criteria

• Age: 6 Months - 25 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must meet all of the following criteria to be eligible for enrollment in the EAP:
• Patients must be aged 6 months to 25 years, inclusive, with a relapsed or refractory low-grade glioma with a documented known or expected to be activating BRAF mutation or RAF fusion, as identified through molecular assays as routinely performed at CLIA-certified or other similarly certified laboratories.
• Patients must have histopathologic diagnosis of glioma or glioneuronal tumor (Grade 1 or 2 according to WHO classification for CNS tumors at either original diagnosis or relapse.
• Patients must have received at least one line of prior systemic therapy and have documented evidence of radiographic progression.
• Previous chemotherapy and/or targeted/immunotherapy/monoclonal antibody therapy must be completed at least 4 weeks or 5 half-lives (whichever is shorter) prior to the initiation of therapy.
• Chronic toxicities from prior anticancer therapy must be stable and at CTCAE Version 5.0 Grade ≤ 2.
• Patients must have fully recovered from any prior surgery.
• Patients must have adequate hematologic function, as defined by the following:
• Absolute neutrophil count≥ 1000/mm3
• Platelet count≥ 75.0 × 109/L
• Hemoglobin≥ 10.0 g/dL (transfusions allowed up to 14 days prior to enrollment per institutional guidelines)
• Patients must have adequate hepatic and renal function, defined by the following:
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN) for age (If patient has documented Gilbert's Disease, patient may be enrolled with Sponsor approval, provided that bilirubin is \< 2.0 × ULN)
• Serum glutamic-pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ≤ 3 × ULN
• Serum glutamic-oxaloacetic transaminase (SGOT)/aspartate transaminase (AST) ≤ 3 × ULN

You may not qualify if:

• Patients meeting any of the following criteria are to be excluded from EAP participation:
• Patient's tumor has an additional previously known or expected to be activating molecular alteration(s) (e.g., histone mutation, IDH1/2 mutations, FGFR mutations or fusions, MYBL alterations, neurofribromatosis type 1 (NF-1) somatic or germline mutations).
• Patient has known or suspected diagnosis of neurofibromatosis type 1 (NF-1) via genetic testing or current diagnostic criteria.
• Patient has history of any major disease, other than the primary malignancy under EAP, that might interfere with safe protocol participation.
• Patient has major surgery within 14 days (2 weeks) prior to C1D1 (does not include central venous access, cyst fenestration or cyst drainage, or ventriculoperitoneal shunt placement or revision).
• Patient has clinically significant active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis/pulmonary embolism within 6 months prior to C1D1, ongoing cardiomyopathy, or current prolonged QT interval corrected for heart rate by Fridericia's formula (QTcF) interval \> 470 milliseconds based on triplicate electrocardiogram (ECG) average.
• Patient has an active systemic bacterial, viral, or fungal infection.
• Patient has malabsorption requiring supplementation, or significant bowel or stomach resection that would preclude adequate absorption of tovorafenib (DAY101).
• Concomitant medications that are strong inhibitors or inducers of CYP2C8 within 14 days before initiation of therapy. Concomitant medications that are substrates of BCRP with a narrow therapeutic index within 14 days before initiation of therapy.
• Patient is pregnant or lactating, or plans to become pregnant in the immediate future.
• Patient has any clinically significant skin toxicity at screening, that in the opinion of the investigator would increase risk of severe skin toxicity when using investigational product.
• There are other unspecified reasons that, in the opinion of the HCP, make the patient unsuitable for enrollment.
• Patient has CTCAE v5.0 Grade ≥3, CPK elevation ( \> 5x UL - 10 X ULN)

Sponsors & Collaborators

• Day One Biopharmaceuticals, Inc.: lead

MeSH Terms

Conditions

Glioma; Neoplasms

Interventions

tovorafenib

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: expanded access
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2023
• First Posted: March 8, 2023
• Last Updated: August 12, 2024

Record last verified: 2024-08