RAF-Altered, Recurrent or Progressive Low-Grade Glioma and Advanced Solid Tumors in pediatric patients.
Conditions
Interventions
Product Name: Tovorafenib
Product Code: DAY101
Pharmaceutical Form: Tablet
INN or Proposed INN: Tovorafenib
CAS Number: 1096708-71-2
Current Sponsor code: DAY101
Other descriptive name: MLN2480, TAK-5
Sponsors
Day One Biopharmaceuticals, Inc. (Day One)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients must be age 6 months to 25 years, inclusive, with: a) Arm 1 (Low-Grade Glioma): A relapsed or progressive low-grade glioma (LGG) with a documented known activating BRAF alteration. b) Arm 2 (Low-Grade Glioma Extension): A relapsed or progressive low-grade glioma with a documented known or expected to be activating BRAF mutation or RAF fusion. c) Arm 3 (Advanced Solid Tumor): Locally advanced or metastatic solid tumor with a documented known or expected to be activating RAF fusion. - Patients must have histopathologic verification of malignancy at either original diagnosis or relapse. - Must have received at least one line of prior systemic therapy and have documented evidence of radiographic progression - Patients must have evaluable and/or measurable disease as specified below: a) Arm 1 (Low-Grade Glioma):Must have at least one measurable lesion. b) Arm 2 (Low-Grade Glioma Extension): Must have evaluable and/or measurable disease c) Arm 3 (Advanced Solid Tumor): Must have at least one measurable lesion - Patients must have Karnofsky (those 16 years and older) or Lansky (those younger than 16 years) performance score of at least 50. For the complete list of the inclusion criteria, please refer to the protocol. Are the trial subjects under 18? yes Number of subjects for this age range: 140 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Patient has symptoms of clinical progression without radiographically recurrent or radiographically progressive disease. - Patient has history of any major disease, other than the primary malignancy under study, that might interfere with safe protocol participation - Patient has major surgery within 14 days (two weeks) prior to C1D1 - Patient has clinically significant active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis/pulmonary embolism within six months prior to C1D1 - Patient is currently enrolled in any other investigational treatment study. Participation in a concurrent observational or bio-sampling study is allowed. For the complete list of the exclusion criteria, please refer to the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Arm 1 (Low-Grade Glioma) To evaluate the efficacy of tovorafenib as measured by the overall response rate as determined by an ind. radiology review committee following treatment with tovorafenib in pediatric patients aged 6 months to 25 years, inclusive, with a relapsed or progressive low-grade glioma (LGG) harboring a known activating BRAF alteration. Arm 2 (Low-Grade Glioma Extension) To assess the safety and tolerability of DAY101 in pediatric patients aged 6 months to 25 years, incl., with a relapsed or progressive low-grade glioma harboring a known or expected to be activating RAF alteration. Arm 3 (Advanced Solid Tumor) To evaluate the preliminary efficacy of DAY101 as measured by the overall response rate (ORR) as determined by an independent radiology review committee (IRC) following treatment with DAY101 in pediatric patients aged 6 months to 25 years, inclusive, with a relapsed or progressive advanced solid tumor harboring a known or expected to be activating RAF fusion.;Secondary Objective: Arm 1 (Low-Grade Glioma): - To assess safety and tolerability of DAY101 - To determine the relationship between pharmacokinetics (PK) and drug effects, including efficacy and safety Arm 2 (Low-Grade Glioma Extension) : - To determine the ORR per Response Assessment in Neuro-Oncology (RANO) criteria as determined by 1) an IRC and 2) the treating investigator - To determine the ORR based on Response Assessment in Pediatric Neuro-Oncology (RAPNO)–low-grade glioma criteria as determined by an IRC Arm 3 (Advanced Solid Tumor) -To assess the safety and tolerability of DAY101 in pediatric patients with advanced solid tumors -To determine the relationship between PK and drug effects, including efficacy and safety For the complete list of secondary objectives please refer to the protocol Section 2 "Study Objectives". ;Primary end point(s): Arm 1 (Low-Grade Glioma): ORR by RANO-HGG criteria Arm 2 (Low-Grade Glioma Extension): Type, frequency, and severity of | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Arm 1 (Low-Grade Glioma): -Type, frequency, and severity of AEs and laboratory abnormalities - Pharmacokinetic profile of DAY101 (e.g., area under the concentration-time curve [AUC], Cmin, etc.) - time following initiation of DAY101 to progression or death in patients treated with DAY101 - length of response in patients with best overall confirmed response of CR or PR - time to first response following initiation of DAY101 in patients with best overall confirmed response of CR or PR Arm 2 (Low-Grade Glioma Extension): - Measured by the proportion of patients with best overall confirmed response of CR or PR as determined by the RANO criteria -Measured by the proportion of patients with best overall confirmed response of CR or PR by RAPNO–low-grade glioma criteria Arm 3 (Advanced Solid Tumor): -Type, frequency, and severity of AEs and laboratory abnormalities -Pharmacokinetic profile of DAY101 (e.g., AUC, Cmin, etc.) For the complete list of secondary endpoints please refer to the protocol ;Timepoint(s) of evaluation of this end point: Please see Appendix A of the protocol for further details. | — |
Countries
Australia, Canada, Denmark, Germany, Israel, Korea, Republic of, Netherlands, Switzerland, United Kingdom, United States
Contacts
Public ContactMelissa Kenny
Parexel International (IRL) Limited
Outcome results
None listed