A Study to Evaluate Tovorafenib in Pediatric and Young Adult Participants With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors

Phase 2RecruitingNCT04775485

Day One Biopharmaceuticals, Inc.141 enrolled

Overview

This is a Phase 2, multi center, open-label study to evaluate the safety and efficacy of Type II RAF (tovorafenib) in pediatric participants with low-grade glioma or advanced solid tumors. Qualifying genomic alterations will be identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) of 1988 or other similarly certified laboratories prior to enrollment into any of the arms. The study will consist of a screening period, a treatment period, a long-term extension phase, end of treatment (EOT) visit(s), a safety follow-up visit, and long-term follow-up assessments.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

141

Conditions

Low-grade Glioma Advanced Solid Tumor

Interventions

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 25 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Low Grade Glioma \& Low-Grade Glioma Extension: a relapsed or progressive LGG with documented known activating BRAF alteration. * Advanced Solid Tumor: locally advanced or metastatic solid tumor with documented known or expected to be activating RAF fusion. * Participants 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. * Must have at least 1 measurable lesion as defined by RANO (Arms 1 \& 2) or RECIST v1.1 (Arm 3) criteria Exclusion Criteria: * Participant's tumor has additional previously-known activating molecular alterations. * Participant has symptoms of without radiographically recurrent or radiographically progressive disease. * Known or suspected diagnosis of neurofibromatosis type 1 (NF-1) via genetic testing or current diagnostic criteria. Other inclusion/exclusion criteria as stipulated by protocol may apply

Locations (35)

UCSF Benioff Children's Hospital

San Francisco, California, United States

RECRUITING

Children's National Medical Center

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

RECRUITING

Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

RECRUITING

Johns Hopkins Hospital

Baltimore, Maryland, United States

Outcomes

Primary Outcomes

Arm 1: Overall response rate

ORR is defined as percentage of participants with best overall confirmed response of complete response (CR) or partial response (PR) by the Response Assessment in Neuro-Oncology - high-grade glioma (RANO-HGG) criteria.

Time frame: Up to 48 months

Arm 2: Number of participants reporting adverse events

An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Time frame: Up to 48 months

Arm 2: Number of participants with clinically significant changes in clinical chemistry parameters

Time frame: Up to 48 months

Arm 2: Number of participants with clinically significant changes in hematology parameters

Time frame: Up to 48 months

Arm 3: Overall response rate

Determined by the treating investigator and measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or RANO-HGG criteria, as appropriate.

Time frame: Up to 48 months

Secondary Outcomes

Arm 1 and 3: Number of participants reporting adverse events

Time frame: Up to 48 months

Arm 1 and 3: Number of participants with clinically significant changes in clinical chemistry parameters

Time frame: Up to 48 months

Arm 1 and 3: Number of participants with clinically significant changes in hematology parameters

Time frame: Up to 48 months

Arm 1: Area under the concentration-time curve (AUC) of Tovorafenib

Time frame: Cycle 1: Day 1 and Day 15; Cycles 2, 4, 7, 10 and 13: Day 1

Arm 1: Minimum drug concentration (Cmin)

Time frame: Cycle 1: Day 1 and Day 15; Cycles 2, 4, 7, 10 and 13: Day 1

Arm 1: Change from Baseline QT interval corrected for heart rate by Fridericia's formula (ΔQTcF)

Time frame: Baseline to 48 months

Arm 1: Change from Baseline PR interval (ΔPR)

Time frame: Baseline to 48 months

Arm 1: Change from Baseline QRS interval (ΔQRS)

Time frame: Baseline to 48 months

Arm 1: Change from baseline heart rate (ΔHR)

Time frame: Baseline to 48 months

Arm 1: Change in electrocardiogram (ECG) waveform morphology

Time frame: Baseline to 48 months

Arm 1 and Arm 2: Overall response rate

ORR is defined as percentage of participants with best overall confirmed response of CR or PR by the RANO-HGG criteria.

Time frame: Up to 48 months

Arm 1, Arm 2 and Arm 3: Overall response rate in Pediatric participants

ORR is defined as percentage of participants with best overall confirmed response of CR or PR or minor response (MR) by Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria.CR or PR by RECIST v1.1 criteria.

Time frame: Up to 48 months

Arm 1, Arm 2 and Arm 3: duration of progression-free survival (PFS)

PFS as defined by the time following initiation of tovorafenib to progression or death in participants treated with tovorafenib measured by RECIST v1.1, RAPNO, or RANO-HGG criteria as determined by the treating investigator and an IRC.

Time frame: Up to 48 months

Arm 1, Arm 2 and Arm 3: Duration of response (DOR)

DOR as defined by the length of response in participants with best overall confirmed response of CR or PR or MR and measured by RANO-HGG, RAPNO, and/or RECIST v1.1 criteria, as applicable.

Time frame: Up to 48 months

Arm 1, Arm 2 and Arm 3: Time to response (TTR)

TTR as defined as the time to first response following initiation of tovorafenib in participants with best overall confirmed response of CR or PR measured by RECIST v1.1 or RANO-HGG criteria, as applicable.

Time frame: Up to 48 months

Arm 1, Arm 2 and Arm 3: Clinical benefit rate (CBR)

CBR as defined as participants with BOR of CR, PR or stable disease (SD) measured by RECIST v1.1 or RANO-HGG, as applicable, and lasting 12 months or more following initiation of tovorafenib.

Time frame: Up to 48 months

Arm 1 and Arm 2: Duration of overall survival

Overall survival as defined by the time following initiation of tovorafenib to death of any cause in participants treated with tovorafenib.

Time frame: Up to 48 months

Arm 1: Change from baseline in best corrected visual acuity (BCVA) outcomes

Time frame: Baseline to 48 months

Arm 1: Changes in molecular analysis of cells obtained from archival tissue

Time frame: At Screening

A Study to Evaluate Tovorafenib in Pediatric and Young Adult Participants With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors

Overview

Conditions

Interventions

Eligibility

Locations (35)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts