TOVORAFENIB for Low-grade glioma | Advanced solid tumor

Inclusion criteria

• {"criterion_text":"- 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.\n- Patients must have histopathologic verification of malignancy at either original diagnosis or relapse.\n- Must have received at least one line of prior systemic therapy and have documented evidence of radiographic progression (Arm 1 and Arm 2).\n- 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\n- Patients must have Karnofsky (those 16 years and older) or Lansky (those younger than 16 years) performance score of at least 50."}

Exclusion criteria

• {"criterion_text":"- Patient has symptoms of clinical progression without radiographically recurrent or radiographically progressive disease.\n- Patient has history of any major disease, other than the primary malignancy under study, that might interfere with safe protocol participation\n- Patient has major surgery within 14 days (2 weeks) prior to C1D1\n- Patient has clinically significant active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis/pulmonary embolism within 6 months prior to C1D1\n- Patient is currently enrolled in any other investigational treatment study. Participation in a concurrent observational or bio-sampling study is allowed."}

Primary endpoints

• {"endpoint_text":"- Arm 1 (Low-Grade Glioma): ORR by RANO-HGG criteria; Arm 2 (Low-Grade Glioma Extension): Type, frequency, and severity of adverse events (AEs) and laboratory abnormalities; Arm 3 (Advanced Solid Tumor): Measured by the proportion of patients with best overall confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 or RANO-HGG criteria","definition_or_measurement_approach":"Arm 1: Overall response rate (ORR) assessed by RANO-HGG criteria as determined by an independent radiology review committee (IRC). Arm 2: Safety endpoints assessed by type, frequency and severity of AEs and laboratory abnormalities. Arm 3: Proportion of patients with best overall confirmed response (CR or PR) per RECIST v1.1 or RANO-HGG criteria as determined by treating investigator."}

Secondary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Safety: described by type, frequency and severity of AEs and lab abnormalities. PK: PK parameters such as AUC, Cmin. Efficacy time-to-event measures: time to progression or death, duration of response, time to first response."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Efficacy measured by proportion of patients with best overall confirmed CR or PR per RANO or RAPNO-low-grade glioma criteria as determined by treating investigator."}
• {"endpoint_text":"- Arm 3 (Advanced Solid Tumor): Type, frequency, and severity of AEs and laboratory abnormalities; Pharmacokinetic profile of DAY101 (e.g., AUC, Cmin, etc.)","definition_or_measurement_approach":"Safety described by type/frequency/severity of AEs and labs; PK parameters such as AUC, Cmin measured for DAY101."}

Germany

Earliest CTIS Part Ii Submission Date

11-07-2024

Latest Decision Or Authorization Date

27-06-2025

Processing Time Days

351

Number Of Sites

2

Number Of Participants

4

Denmark

Earliest CTIS Part Ii Submission Date

11-07-2024

Latest Decision Or Authorization Date

23-06-2025

Processing Time Days

347

Number Of Sites

1

Number Of Participants

2

Netherlands

Earliest CTIS Part Ii Submission Date

11-07-2024

Latest Decision Or Authorization Date

21-07-2025

Processing Time Days

375

Number Of Sites

1

Number Of Participants

10

Primary sponsor

Full Name

Day One Biopharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Iqvia Biotech Limited

Responsibilities

706618; 706619; 706620; 706621 (codes only provided) - EU CTIS support and multiple CRO responsibilities as listed

Name

PPD Development LP

Responsibilities

Release Testing (tablets, powder for reconstitution); Stability Testing (tablets, powder for reconstitution)

Name

ClinChoice, Inc.

Responsibilities

706611 (code only provided)

Name

Almac Clinical Technologies LLC

Responsibilities

706617 (code only provided)

Name

Medidata Solutions Inc.

Responsibilities

706612 (code only provided)

Name

Certara USA Inc.

Responsibilities

Population pharmacokinetic (PK) modeling and reporting

Third parties

• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient travel booking and reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Central electrocardiogram (ECG)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Quotient Sciences Philadelphia LLC","duties_or_roles":"Manufacturing (tablets, powder for reconstitution) Release testing (powder for reconstitution) Stability testing (powder for reconstitution)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"QP Release - EU (tablets, powder for reconstitution)","organisation_type":"Pharmaceutical company"}
• {"country":"China","full_name":"Shanghai Syntheall Pharmaceutical Co. Ltd.","duties_or_roles":"Manufacture, testing, and stability of Regulatory Starting Materials (APMA and CTPH) Manufacture and Packaging of DAY101 Drug Substance Release and Stability Testing of DAY101","organisation_type":"Pharmaceutical company"}
• {"country":"Japan","full_name":"Yonezawa Hamari Chemicals Ltd.","duties_or_roles":"Manufacturing of Final Intermediate R-APT","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"706609 (code only provided)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Inseption Group LLC","duties_or_roles":"706610 (code only provided)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Release Testing (tablets, powder for reconstitution) Stability Testing (tablets, powder for reconstitution)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Certara USA Inc.","duties_or_roles":"Population pharmacokinetic (PK) modeling and reporting","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"706606 (code only provided)","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Clinical Logistics Inc.","duties_or_roles":"Lab kits and manual for pharmacokinetics (PK) and tumor samples","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Fisher Clinical Services UK Limited","duties_or_roles":"Packaging and Labeling (tablets, powder for reconstitution) QP Release - UK (tablets, podwer for reconstitution)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"Tumor Sample Repository","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Experic LLC","duties_or_roles":"Packaging and Labeling (tablets, powder for reconstitution)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"ClinChoice, Inc.","duties_or_roles":"706611 (code only provided)","organisation_type":"Industry"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"706612 (code only provided)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"QPS LLC","duties_or_roles":"706627 (code only provided)","organisation_type":"Pharmaceutical company"}
• {"country":"Japan","full_name":"Fujimoto Chemicals Co. Ltd.","duties_or_roles":"Manufacturing and Packaging of DAY101 drug substance","organisation_type":"Pharmaceutical company"}
• {"country":"Japan","full_name":"Sumika Chemical Analysis Service Ltd.","duties_or_roles":"Release and Stability Testing","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Tumor Sample Repository","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Imaging Endpoints II LLC","duties_or_roles":"Central imaging","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"706617 (code only provided)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Iqvia Biotech Limited","duties_or_roles":"706618; 706619; 706620; 706621 (codes only provided)","organisation_type":"Pharmaceutical company"}