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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05760586
Expanded Access Status : Available
First Posted : March 8, 2023
Last Update Posted : March 8, 2023
Information provided by (Responsible Party):
Day One Biopharmaceuticals, Inc.

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

Condition or disease Intervention/treatment
Low-grade Glioma Drug: Tovorafenib

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Study Type : Expanded Access
Expanded Access Type : Treatment IND/Protocol
Official Title: Expanded Access to the Oral Pan-RAF Inhibitor DAY101 in Pediatric Patients With RAF-Altered, Relapsed or Refractory Low-Grade Glioma

Intervention Details:
  • Drug: Tovorafenib
    Oral pan-RAF inhibitor provided as an immediate-release tablet (100 mg) or powder for reconstitution (25 mg/mL)
    Other Name: DAY101

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   6 Months to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All

Inclusion Criteria:

Patients must meet all of the following criteria to be eligible for enrollment in the EAP:

  1. Patients must be aged 6 months to 25 years, inclusive, with a relapsed or progressive 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.
  2. Patients must have histopathologic verification of malignancy at either original diagnosis or relapse.
  3. Patients must have received at least one line of prior systemic therapy and have documented evidence of radiographic progression.
  4. Patients must have fully recovered from the acute toxic effects of all prior anticancer chemotherapy.
  5. Chronic toxicities from prior anticancer therapy must be stable and at CTCAE Version 5.0 Grade ≤ 2.
  6. Patients must have fully recovered from any prior surgery.
  7. Patients must have adequate hematologic function, as defined by the following:

    1. Absolute neutrophil count≥ 1000/mm3
    2. Platelet count≥ 75.0 × 109/L (transfusions allowed per institutional guidelines)
    3. Hemoglobin≥ 10.0 g/dL (transfusions allowed per institutional guidelines)
  8. Patients must have adequate hepatic and renal function, defined by the following:

    1. 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)
    2. Serum glutamic-pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ≤ 3 × ULN
    3. Serum glutamic-oxaloacetic transaminase (SGOT)/aspartate transaminase (AST) ≤ 3 × ULN
    4. Serum creatinine within normal limits, or estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2 based on local institutional practice for determination
  9. Thyroid function tests must be consistent with stable thyroid function.
  10. Patients must be able to comply with treatment, laboratory monitoring, and required clinic visits for the duration of EAP participation.
  11. Female patients with reproductive potential must be willing to use a highly effective birth control method for the duration of treatment and for 4 weeks or 28 days following the last dose of EAP drug. Males must be willing to utilize a condom during intercourse for 14 weeks following the last dose of the EAP drug.
  12. Patients must have ability to swallow tablets or liquid or be willing to comply with administration of a nasal or gastric tube for gastric access.
  13. Parent/guardian of child or adolescent patient must have the ability to understand, agree to, and sign the EAP informed consent form (ICF) and applicable pediatric assent form before initiation of any treatment-related procedures; patient must have the ability to give assent, as applicable, at the time of parental/guardian consent.

Exclusion Criteria:

Patients meeting any of the following criteria are to be excluded from EAP participation:

  1. 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, NF-1 somatic or germline mutations).
  2. Patient has known or suspected diagnosis of neurofibromatosis type 1 (NF-1) via genetic testing or current diagnostic criteria.
  3. Patient has history of any major disease, other than the primary malignancy under EAP, that might interfere with safe protocol participation.
  4. 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).
  5. 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.
  6. Patient has an active systemic bacterial, viral, or fungal infection.
  7. Patient has malabsorption requiring supplementation, or significant bowel or stomach resection that would preclude adequate absorption of DAY101.
  8. Patient is currently being treated with a strong CYP2C8 inhibitor or inducer other than those allowed per Appendix C Medications that are substrates of CYP2C8 are allowed but should be used with caution.
  9. Patient is pregnant or lactating, or plans to become pregnant in the immediate future.
  10. Patient has a history of any drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome or Stevens Johnsons syndrome (SJS), or hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of the investigational medicinal product.
  11. There are other unspecified reasons that, in the opinion of the HCP, make the patient unsuitable for enrollment.
  12. Patient has CTCAE v5.0 Grade ≥ 3, CPK elevation (> 5 × ULN - 10 × ULN).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05760586

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Contact: WEP Clinical 919-694-5088

Sponsors and Collaborators
Day One Biopharmaceuticals, Inc.
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Responsible Party: Day One Biopharmaceuticals, Inc. Identifier: NCT05760586    
Other Study ID Numbers: DAY101-EAP
First Posted: March 8, 2023    Key Record Dates
Last Update Posted: March 8, 2023
Last Verified: February 2023
Keywords provided by Day One Biopharmaceuticals, Inc.:
BRAF Mutation
RAF Alteration
Type II BRAF Inhibitor
Additional relevant MeSH terms:
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Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue