DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)

Progression-free survival (PFS) of tovorafenib monotherapy versus SoC chemotherapy

PFS assessed per RAPNO criteria by IRC, and defined as time from randomization to PD or death from any cause, whichever comes first.

Time frame: Up to 60 months

Event-free survival (EFS) of tovorafenib monotherapy versus SoC chemotherapy

EFS assessed per RAPNO criteria by IRC, defined as time from randomization to PD, death from any cause, or initiation of any new anticancer therapy, whichever comes first.

Time frame: Up to 60 months

Overall survival (OS) of tovorafenib monotherapy versus SoC chemotherapy

Overall survival is defined as time from randomization up to death from any cause.

Time frame: Up to 60 months

Number of participants with any treatment-emergent adverse events, and Serious adverse events

Type, frequency, and severity of adverse events of tovorafenib monotherapy versus SoC chemotherapy will be assessed.

Time frame: Up to 60 months

. Number of participants with clinically significant vital signs and laboratory abnormalities findings

Type, frequency, and severity of vital signs and laboratory abnormalities of tovorafenib monotherapy versus SoC chemotherapy will be assessed.

Time frame: Up to 60 months

Change from baseline in Adaptive Behavior Composite Score (ABS) of tovorafenib monotherapy versus SoC chemotherapy

Adaptive behavior Composite Score will be evaluated using domain scores collected from the comprehensive Vineland III Adaptive Behavior Scale (VABS).

Time frame: Baseline, Year 1, 2 and 5

Change from baseline in the Motor Skills Domain Score of tovorafenib monotherapy versus SoC chemotherapy

The motor skills (gross and fine) will be assessed using the Motor Skills Score domain of the VABS in pediatric participants.

Time frame: Baseline, Year 1, 2 and 5

Change from baseline in the Daily Living Domain Score of tovorafenib monotherapy versus SoC chemotherapy

The daily living (personal, domestic and community) will be assessed using Daily Living Domain Score of VABS.

Time frame: Baseline, Year 1, 2 and 5

Change from baseline in the Communication Domain Score of tovorafenib monotherapy versus SoC chemotherapy

The communication skills (receptive, expressive and written) will be assessed using Communication Domain Score of VABS.

Time frame: Baseline, Year 1, 2 and 5

Change from baseline in the Socialization Domain Score of tovorafenib monotherapy versus SoC chemotherapy

The socialization skills (Interpersonal relationships, play and leisure time and coping skills) will be assessed using Socialization Domain Score of VABS.

Time frame: Baseline, Year 1, 2 and 5

Change in age-adjusted visual acuity (VA) of tovorafenib monotherapy versus SoC chemotherapy in optic pathway glioma (OPG) participants aged < 3 years

Visual acuity testing using current age-appropriate testing methodology will be performed for all participants at Screening. For participants with OPG or an underlying visual deficit related to the primary malignancy, visual acuity testing will be performed every time participants have a radiographic response assessment. Assessments will be performed in each eye separately at a recommended testing distance of 3 meters.

Time frame: Baseline and up to 5 years

Change in best corrected visual acuity of tovorafenib monotherapy versus SoC chemotherapy in OPG participants aged ≥ 3 years

Visual acuity assessments to be performed by an ophthalmologist or another qualified site clinical personnel.

Time frame: Baseline and up to 5 years

Visual progression-free survival (v-PFS) of tovorafenib monotherapy versus SoC chemotherapy

Visual progression-free survival is defined as the time from start of treatment to visual event for OPG participants aged ≥ 3 years.

Time frame: Up to 60 months

ORR of tovorafenib monotherapy versus SoC chemotherapy

ORR, defined as the proportion of participants with overall confirmed response per Response Assessment in Neuro-Oncology for High-Grade Glioma (RANO-HGG) criteria (CR or PR) and RANO-LGG criteria (CR, PR, or MR), as applicable.

Time frame: Up to 60 months

Clinical benefit rate (CBR) of tovorafenib monotherapy versus SoC chemotherapy

CBR, defined as the proportion of participants with radiological tumor stabilization or regression per RANO-LGG (CR, PR, MR, or SD lasting 12 months or more), RANO-HGG (CR, PR, or SD lasting 12 months or more) or RAPNO criteria (CR, PR, MR or SD lasting 12 months or more), as applicable.

Time frame: Up to 60 months

Time to response (TTR) of tovorafenib monotherapy versus SoC chemotherapy

TTR, measured by the time following randomization to first imaging of tumor response that was subsequently confirmed per RANO-HGG criteria (CR or PR), RANO-LGG criteria (CR, or PR, or MR), or RAPNO criteria (CR, PR, or MR), as applicable.

Time frame: Up to 60 months

PFS of tovorafenib monotherapy versus SoC chemotherapy

PFS per RANO-HGG or RANO-LGG criteria (as applicable), defined as time from randomization to PD or death from any cause, whichever occurs first.

Time frame: Up to 60 months

EFS of tovorafenib monotherapy versus SoC chemotherapy

EFS per RANO-HGG or RANO-LGG criteria (as applicable), defined as time from randomization to PD, death from any cause, or initiation of any new anticancer therapy, whichever comes first.

Time frame: Up to 60 months

Duration of response (DOR) of tovorafenib monotherapy versus SoC chemotherapy

DOR, defined as time from first imaging of tumor response per RANO-LGG, RANO-HGG or RAPNO criteria, as applicable, that was subsequently confirmed to radiographic PD or death from any cause, whichever comes first.

Time frame: Up to 60 months

Change from Baseline in health-related quality of life (HRQoL) total score of tovorafenib monotherapy versus SoC chemotherapy

The Patient-Reported Outcomes Measurement Information System (PROMIS®) Pediatric/Parent Proxy Profile 49 v2.0 will be used to assess mental and social HRQoL.

Time frame: Baseline, Year 1, 2 and 5