A Study to Evaluate Tovorafenib in Pediatric and Young Adult Participants With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors (FIREFLY-1)

Day One Biopharmaceuticals

Status and phase: Enrolling; Phase 2

Conditions: Low-grade Glioma; Advanced Solid Tumor

Treatments: Drug: Tovorafenib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04775485

DAY101-001/PNOC026

Details and patient eligibility

About

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.

Enrollment: 141 estimated patients

Sex: All

Ages: 6 months to 25 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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141 participants in 3 patient groups

Arm 1: Low-Grade Glioma

Experimental group

Description:

Participants with recurrent or progressive low-grade glioma will receive 420 milligrams/meters square (mg/m\^2) of tovorafenib weekly according to dose rounding guidelines and according to their baseline body surface area (BSA).

Treatment:

Drug: Tovorafenib

Arm 2: Low-Grade Glioma Expanded Access

Experimental group

Description:

Participants with recurrent or progressive low-grade glioma will receive 420 mg/m\^2 of tovorafenib weekly according to dose rounding guidelines and according to their baseline BSA.

Treatment:

Drug: Tovorafenib

Arm 3: Advanced Solid Tumor

Experimental group

Description:

Participants with advanced solid tumors will receive 420 mg/m\^2) of tovorafenib weekly according to dose rounding guidelines and according to their baseline BSA.

Treatment:

Drug: Tovorafenib