FIREFLY-1: A Phase 2, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of the Oral Pan-RAF Inhibitor DAY101 in Pediatric Patients With RAF-Altered, Recurrent or Progressive Low-Grade Glioma and Advanced Solid Tumors
Phase: PHASE2
Conditions: Low-grade Glioma, Advanced Solid Tumor
Sponsor: Day One Biopharmaceuticals, Inc.



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DOT Therapeutics-1 Inc. (Day One) 
Clinical Protocol DAY101-001 
DAY101 
21 Oct 2021 
Version 3.0 Final 
Confidential & Proprietary 
Page 3 of 138 
PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Protocol DAY101-001 has been amended primarily to add two new arms to the study, add a 
powder for reconstitution formulation of DAY101, and incorporate changes based on 
feedback from regulatory authorities. 
Section(s) 
Description of Change 
Brief Rationale 
Synopsis 
The protocol synopsis has been updated to reflect 
the changes in the protocol. 
For consistency with revisions. 
Global 
Two new arms have been added to the protocol: 
Arm 2 is an extension cohort to enroll patients with 
a low-grade glioma harboring an activating RAF 
alteration (e.g., BRAF or CRAF/RAF1 fusion or 
BRAF V600 mutations) and will provide treatment 
options to patients following the closure of Arm 1 
and prior to commercial availability of DAY101. 
Arm 3 will enroll patients with advanced solid 
tumors harboring activating RAF fusions (e.g., 
BRAF or CRAF/RAF1 fusions). 
The background, rationale, objectives, design, 
eligibility criteria, assessments, and statistical 
analyses sections have been revised to incorporate 
these new arms. 
Based on data obtained from other 
DAY101 studies and feedback from 
health authority. 
Global 
1.1.1, 1.1.2, 
1.2.1, 1.3.1 
The introduction has been revised to refer to BRAF 
fusion instead of BRAF wild-type fusion. 
Administrative clarification. 
1.1.2 
The summary of pediatric low-grade gliomas has 
been updated. 
To include additional background on 
disease and treatment-related 
morbidities in patients with pediatric 
low-grade glioma. 
1.3.3 
The benefit/risk assessment has been revised to 
include a summary of risks from nonclinical studies 
and the Phase 1 clinical study, dosing 
considerations, drug metabolism, considerations for 
required study procedures for the pediatric 
population, the safety monitoring and risk 
management plan, a summary of potential benefits, 
and an integrated benefit/risk assessment. 
Based on feedback from health 
authority. 
2 
The RAPNO criteria will be determined by the IRC 
only (Arms 1 and 2). 
Administrative clarification. 
2, 6.9.2, 7.3.3 
The Pediatrics Quality of Life™—Cancer has been 
specified as a health-related QoL assessment. 
Administrative clarification for 
consistency with planned study 
objectives. 

DOT Therapeutics-1 Inc. (Day One) 
Clinical Protocol DAY101-001 
DAY101 
21 Oct 2021 
Version 3.0 Final 
Confidential & Proprietary 
Page 5 of 138 
Section(s) 
Description of Change 
Brief Rationale 
5.2.1 
The restriction with regard to intake of food has 
been removed: patients can now be fed or fasted. 
Clarified that the dose of study intervention should 
be increased or decreased for any change in body 
surface area (BSA) greater than 10%. 
Administrative clarification. 
5.2.3.2 
Added instruction for patients to monitor for signs 
and symptoms of photosensitivity. 
Based on feedback from health 
authority. 
5.2.3.5 
The increased liver transaminase recommendation 
IRUDV\PSWRPDWLF Grade 3 AST or ALT 
AND > 2 × increase from baseline has been revised 
to “withhold DAY101 until the laboratory 
abnormality resolves to < 5 × ULN or baseline” 
rather than “withhold DAY101 until the laboratory 
abnormality resolves to < 5 × ULN AND baseline.” 
Administrative clarification. 
5.3.2, 6.17, 
8.2 
Additional references to the safety run-in portion of 
the study have been removed. 
For consistency with the removal of 
the safety run-in in V2.0 of the 
protocol. 
5.3.3 
Herbal supplements are now prohibited during the 
study. 
Based on feedback from the local 
review board 
5.3.3, 
Appendix C 
Medications that are substrates of breast cancer 
resistance protein (BCRP) have been added as 
prohibited concomitant medications. A table of 
BCRP substrates was added to Appendix C. 
Based on feedback from health 
authority. 
6.6.4, 6.9.1.2, 
Appendix A 
On-treatment ophthalmology examinations and 
visual acuity assessments have been clarified to be 
only required for patients with optic pathway glioma 
or patients with underlying visual deficits related to 
the primary malignancy. For all other patients, 
examinations are only required at screening, and 
symptom-directed examinations may be completed 
at subsequent visits. 
For consistency with standard 
clinical practice. 
6.6.7 
Added assessments of pubertal development 
according to the Tanner Stages. 
Based on feedback from health 
authority. 
6.6.8.1 
Required echocardiogram/ multiple-gated 
acquisition and 12-lead electrocardiogram 
assessments were added at the end of treatment 
(EOT) visit. 
Based on feedback from health 
authority. 
6.7.3 
Phosphorous will now be assessed as part of the 
serum chemistry panel. 
International normalized ratio, cholesterol, and 
direct bilirubin will no longer be assessed. 
To follow as part of regular safety 
monitoring. 
To reduce unnecessary analyte 
collection. 
6.7.4 
Thyroid stimulating hormone (TSH) will now be 
assessed as part of the thyroid function tests. 
To ensure comprehensive monitoring 
of thyroid function. 

DOT Therapeutics-1 Inc. (Day One) 
Clinical Protocol DAY101-001 
DAY101 
21 Oct 2021 
Version 3.0 Final 
Confidential & Proprietary 
Page 8 of 138 
Exploratory Objectives: 
x
To compare the response and time to progression following initiation of DAY101 to that of the prior
line of systemic therapy
x
To characterize changes in total tumor volume following treatment with DAY101 by magnetic
resonance imaging (MRI) volumetric image analysis
x
To characterize changes in apparent diffusion coefficients following treatment with DAY101 using
diffusion-weighted imaging analysis
x
To evaluate changes in quality of life and health utilities measures using the Pediatrics Quality of
Life™—Core (PedsQL-Core), Pediatrics Quality of Life™—Cancer (PedsQL-Cancer), and
Patient-Reported Outcomes Measurement Information System (PROMIS®) assessment
x
To describe improvement in motor function
x
To determine the durability of response following discontinuation of DAY101 for patients with a
radiographic response to DAY101 (CR or PR as based on RANO and RAPNO criteria) as
determined by 1) an IRC and 2) the treating investigator (RANO only)
x
To evaluate time to initiation of next treatment following discontinuation of DAY101
ARM 2 (LOW-GRADE GLIOMA EXTENSION) OBJECTIVES 
Primary Objective: 
The primary objective of Arm 2 is to assess the safety and tolerability of DAY101 in pediatric patients aged 6 
months to 25 years, inclusive, with a relapsed or progressive low-grade glioma harboring a known or 
expected to be activating RAF alteration. 
Secondary Objectives: 
x
To determine the ORR based on RANO criteria as determined by 1) an IRC and 2) the treating
investigator
x
To determine the ORR based on RAPNO–low-grade glioma criteria as determined by an IRC
x
To evaluate the duration of PFS based on RANO and RAPNO criteria following initiation of
DAY101 as determined by 1) an IRC and 2) the treating investigator (RANO only)
x
To evaluate the DOR in patients with BOR of CR or PR based on RANO and RAPNO criteria as
determined by 1) an IRC and 2) the treating investigator (RANO only)
x
To evaluate TTR (CR or PR based on RANO and RAPNO criteria) following initiation of DAY101
as determined by 1) an IRC and 2) the treating investigator (RANO only)
x
To evaluate the clinical benefit rate based on the proportion of patients with BOR of CR, PR, or SD,
based on RANO and RAPNO criteria, lasting 12 months or more following initiation of DAY101, as
determined by 1) an IRC and 2) the treating investigator (RANO only)
x
To determine the relationship between PK and drug effects, including efficacy and safety
x
To evaluate the effect of DAY101 on QTcF prolongation and to explore the effects of DAY101 on
ECG parameters

DOT Therapeutics-1 Inc. (Day One) 
Clinical Protocol DAY101-001 
DAY101 
21 Oct 2021 
Version 3.0 Final 
Confidential & Proprietary 
Page 10 of 138 
STUDY DESIGN: 
This is a Phase 2, multicenter, multi-arm, open-label study evaluating DAY101 in pediatric patients with 
low-grade gliomas and advanced solid tumors. The study will consist of the following treatment arms: 
x
Arm 1 (Low-Grade Glioma): Patients aged 6 months to 25 years, inclusive, with recurrent or
progressive low-grade glioma harboring a known activating BRAF alteration, including BRAF V600
mutations and KIAA1549:BRAF fusions. Patients with BRAF alterations will be identified through
molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA)
of 1988 or other similarly certified laboratories.
x
Arm 2 (Low-Grade Glioma Extension): Patients aged 6 months to 25 years, inclusive, with
recurrent or progressive low-grade glioma harboring a known or expected to be activating RAF
alteration (e.g., BRAF or CRAF/RAF1 fusion or BRAF V600 mutations). Patients with RAF
alterations will be identified through molecular assays as routinely performed at CLIA-certified or
other similarly certified laboratories. Opening of Arm 2 to enrollment will be based on the
recommendation of the Data Safety Monitoring Board (DSMB) as described in the protocol.
x
Arm 3 (Advanced Solid Tumor): Patients aged 6 months to 25 years, inclusive, with advanced
solid tumors harboring a known or expected to be activating RAF fusion (e.g., BRAF or
CRAF/RAF1 fusion). Patients with RAF fusions will be identified through molecular assays as
routinely performed at CLIA-certified or other similarly certified laboratories.
For all arms, treatment cycles will repeat every 28 days in the absence of disease progression or unacceptable 
toxicity. Patients will continue on DAY101 until radiographic evidence of disease progression as determined 
by treating investigator, unacceptable toxicity, decision to enter a “drug holiday” period, patient withdrawal 
of consent, or death. 
Patients will be treated with DAY101 for a planned period of 26 cycles (approximately 24 months), after 
which they may continue on DAY101 or, at any point, opt to enter a “drug holiday” discontinuation period. 
Patients will continue to undergo routine periodic radiographic evaluations per protocol-defined timelines 
during the discontinuation period and may be re-treated with DAY101 if there is radiographic evidence of 
disease progression after drug discontinuation. 
Patients who have radiographic evidence of disease progression may be allowed to continue DAY101 if, in 
the opinion of the investigator, and approved by the Sponsor, the patient is deriving clinical benefit from 
continuing study treatment. Patients being treated beyond progression with DAY101 will be reconsented 
prior to continuation of therapy. Disease assessments for patients being treated beyond progression should 
continue as per regular schedule. 
The study will consist of a screening period, a treatment period, an end of treatment (EOT) visit, a safety 
follow-up visit, and long-term follow-up assessments. Ongoing safety, disease stability/progression, survival, 
and subsequent anticancer therapies will be assessed in the long-term follow-up period. 
DAY101 will be administered at the recommended Phase 2 dose (RP2D) of 420 mg/m2 (not to exceed 
600 mg), orally (PO) once weekly (QW) (Days 1, 8, 15, and 22 of a 28-day cycle). Body surface area (BSA) 
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tablet or reconstituted liquid suspension formulation. 
MAJOR ELIGIBILITY CRITERIA: 
INCLUSION CRITERIA 
Patients must meet all of the following criteria to be eligible for enrollment in the study: 
1.
Patients must be age 6 months to 25 years, inclusive, with:
a)
Arm 1 (Low-Grade Glioma): A relapsed or progressive low-grade glioma with a documented
known activating BRAF alteration, as identified through molecular assays as routinely
performed at CLIA or other similarly certified laboratories
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, as identified

DOT Therapeutics-1 Inc. (Day One) 
Clinical Protocol DAY101-001 
DAY101 
21 Oct 2021 
Version 3.0 Final 
Confidential & Proprietary 
Page 11 of 138 
through molecular assays as routinely performed at CLIA-certified or other similarly certified 
laboratories 
c)
Arm 3 (Advanced Solid Tumor): Locally advanced or metastatic solid tumor with a documented
known or expected to be activating RAF fusion, as identified through molecular assays as
routinely performed at CLIA-certified or other similarly certified laboratories, that has relapsed
or progressed or was nonresponsive to available therapies and for which no standard or
available systemic curative therapy exists
2.
Patients must have histopathologic verification of malignancy at either original diagnosis or relapse.
3.
Patients must have received at least one line of prior systemic therapy and have documented evidence of
radiographic progression.
4.
Patients must have evaluable and/or measurable disease (imaging must be performed within 28 days of
the initiation of treatment) as specified below:
a)
Arm 1 (Low-Grade Glioma): Must have at least one measurable lesion as defined by RANO
criteria (T1-weighted lesion that can be reproducibly measured in at least 2 dimensions of at
least 10 mm, visible on 2 or more axial slices that are preferably, at most, 5 mm apart with
0-mm skip)
b)
Arm 2 (Low-Grade Glioma Extension): Must have evaluable (either unidimensionally
measurable lesions, masses with margins not clearly defined, or lesions with maximal
perpendicular diameters less than 10 mm) and/or measurable disease as defined by RANO
criteria
c)
Arm 3 (Advanced Solid Tumor): Must have at least one measurable lesion as defined by
5(&,67Y 10 PPE\&705,VFDQ>VOLFHWKLFNQHVV 5 PP@ 20 mm by chest X-ray, or
 10 mm with calipers by clinical exam; or pathologic lymph nodes with a short axis of
 15 mm by CT scan/MRI)
5.
Radiation therapy to the measurable lesion(s) must be completed at least six months prior to
administration of DAY101. Patients who have documented radiographic progression less than six months
from radiotherapy in one or more measurable lesions are eligible.
6.
Patients must have Karnofsky (those 16 years and older) or Lansky (those younger than 16 years)
performance score of at least 50. Patients who are unable to walk because of paralysis, but who are able
to sit in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
7.
Patients must have fully recovered from the acute toxic effects of all prior anticancer chemotherapy and
have undergone the following washout periods, as applicable:
a)
Myelosuppressive chemotherapy: At least 21 days must have elapsed after the last dose of
myelosuppressive chemotherapy (42 days if prior nitrosourea).
b)
Radiation therapy (XRT): At least 14 days must have elapsed after the last dose fraction of
XRT.
c)
Stem cell transplant or adoptive cell therapy: At least 100 days must have elapsed after cell
infusion.
d)
Investigational agent or any other anticancer therapy not defined above: At least four weeks
prior to planned start of DAY101 or five half-lives, whichever is shorter.
8.
Chronic toxicities from prior anticancer therapy must be stable and at Common Terminology Criteria for
Adverse Events (CTCAE) version 5.0 Grade  2.
a)
OQJRLQJUHWLQRSDWK\PXVWEH*UDGH.
9.
Patients must have fully recovered from any prior surgery.
10. An archival tumor tissue sample must be available. If an archival tumor tissue sample is not available, a
fresh biopsy should be performed at baseline. For patients enrolling to Arm 2 (Low-Grade Glioma
Extension) that do not have archival tumor tissue, enrollment may be considered on a case-by-case basis
following a discussion between the investigator and the Day One Medical Monitor.
11. Patients must have adequate hematologic function, as defined by the following:
a)
Absolute neutrophil count  1000/mm3

DOT Therapeutics-1 Inc. (Day One) 
Clinical Protocol DAY101-001 
DAY101 
21 Oct 2021 
Version 3.0 Final 
Confidential & Proprietary 
Page 12 of 138 
b)
Platelet count  75.0 u 109/L (transfusions allowed per institutional guidelines; last transfusion
> 2 weeks prior to C1D1)
c)
Hemoglobin  10.0 g/dL (transfusions allowed per institutional guidelines; last transfusion
> 4 weeks prior to C1D1)
d)
Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor
(e.g., Neulasta®) or seven days for short-acting growth factor
12. Patients must have adequate hepatic and renal function, defined as the following:
a)
Total bilirubin  1.5 u upper limit of normal (ULN) for age (patients with documented Gilbert’s
Disease may be enrolled with Sponsor approval DQGWRWDOELOLUXELQ 2.0 u ULN)
b)
Serum glutamic-pyruvic transaminase (SGPT)/alanine aminotransferase (ALT)  2.5 u ULN
c)
Serum glutamic-oxaloacetic transaminase (SGOT)/aVSDUWDWHWUDQVDPLQDVH$67 2.5 u ULN
d)
Serum creatinine within normal limits, or estimated glomerular filtration rate
 60 mL/min/1.73 m2 based on local institutional practice for determination
13. Thyroid function tests must be consistent with stable thyroid function. Patients on a stable dose of
thyroid replacement therapy for a minimum of three weeks before starting DAY101 are eligible.
14. Patients must have left ventricular ejection fraction (LVEF) of 0% as measured by echocardiogram
(ECHO) or multiple-gated acquisition (MUGA) scanRUIUDFWLRQDOVKRUWHQLQJ)6 25% as measured
by ECHO, within 28 days before the first dose of DAY101. If normal practice at the institution is to
provide the LVEF result as a range of values, then the upper value of the range will be used to determine
the result.
15. Patients receiving steroids for tumor-associated symptoms must be on a stable dose (e.g., no
initial/loading dose, no increase or decrease) for 14 days prior to C1D1.
16. Patients must be able to comply with treatment, laboratory monitoring, and required clinic visits for the
duration of study participation.
17. Male and female patients with reproductive potential must be willing to use a highly effective birth
control method for the duration of treatment and for 180 days following the last dose of study drug.
18. Patients must have ability to swallow tablets or liquid, or be willing to comply with administration of a
nasal or gastric tube for gastric access.
19. Parent/guardian of child or adolescent patient must have the ability to understand, agree to, and sign the
study informed consent form (ICF) and applicable pediatric assent form before initiation of any
protocol-related procedures; patient must have the ability to give assent, as applicable, at the time of
parental/guardian consent.
EXCLUSION CRITERIA 
Patients meeting any of the following criteria are to be excluded from study participation: 
1.
Patient’s tumor has additional previously known or expected to be activating molecular alteration(s)
(e.g., histone mutation, IDH1/2 mutations, FGFR mutations or fusions, MYBL alterations, NF1 somatic
or germline mutations).
2.
Patient has symptoms of clinical progression without radiographically recurrent or radiographically
progressive disease.
3.
Patient has known or suspected diagnosis of neurofibromatosis type 1 (NF-1) via genetic testing or
current diagnostic criteria.
4.
Patient has history of any major disease, other than the primary malignancy under study, that might
interfere with safe protocol participation.
5.
Patient has a history or current evidence of central serous retinopathy (CSR), retinal vein occlusion
(RVO), or ophthalmopathy present at baseline that would be considered a risk factor for CSR or RVO.
Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic
nerve pallor, or strabismus) will NOT be considered a significant abnormality for the purposes of this
study.

DOT Therapeutics-1 Inc. (Day One) 
Clinical Protocol DAY101-001 
DAY101 
21 Oct 2021 
Version 3.0 Final 
Confidential & Proprietary 
Page 13 of 138 
6.
Patient has major surgery within 14 days (two weeks) prior to C1D1 (does not include central venous
access, cyst fenestration or cyst drainage, or ventriculoperitoneal shunt placement or revision).
7.
Patient has clinically significant active cardiovascular disease, or history of myocardial infarction, or
deep vein thrombosis/pulmonary embolism within six months prior to C1D1, ongoing cardiomyopathy,
or current prolonged QT interval corrected for heart rate by Fridericia’s formula (QTcF) interval
> 470 ms based on triplicate ECG average.
8.
Patient is currently enrolled in any other investigational treatment study. Participation in a concurrent
observational or bio-sampling study is allowed.
9.
Patient has active systemic bacterial, viral, or fungal infection.
10. Patient has nausea and vomiting  National Cancer Institute (NCI) Common Terminology Criteria for
Adverse Events (CTCAE) v5.0 Grade 2, malabsorption requiring supplementation, or significant bowel
or stomach resection that would preclude adequate absorption of DAY101.
11. Patient is neurologically unstable despite adequate treatment (e.g., uncontrolled seizures).
12. Patient is currently being treated with a strong cytochrome P450 2C8 (CYP2C8) inhibitor or inducer
other than those allowed per protocol. Medications that are substrates of CYP2C8 are allowed but should
be used with caution.
13. Patient is pregnant or lactating.
14. Patient has a history of any drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome
or Stevens Johnsons syndrome (SJS), or hypersensitivity to the investigational medicinal product or to
any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of
the investigational medicinal product.
15. There are other unspecified reasons that, in the opinion of the investigator, make the patient unsuitable
for enrollment.
PLANNED SAMPLE SIZE: 
Approximately 140 patients in total will be enrolled across all treatment arms of this study. The arms will be 
enrolled as follows: 
Arm 1 (Low-Grade Glioma): Approximately 60 patients 
Arm 2 (Low-Grade Glioma Extension): Up to 60 patients 
Arm 3 (Advanced Solid Tumor): Up to 20 patients 
Patients will be considered enrolled when they have ingested a dose of DAY101 on C1D1. 
INVESTIGATIONAL DRUG: 
DAY101 for oral dosing is provided as an immediate-release tablet in one strength, 100 mg. The 100-mg 
tablets are red to yellowish red oval tablets and are labeled DAY101. In addition, DAY101 is provided in 
bottles as a powder for reconstitution (430 mg per bottle to deliver 300-mg dose) that is reconstituted with 
water to form a suspension with a concentration of 25 mg/mL. 
TREATMENT PROCEDURES: 
Patients will initiate treatment at the RP2D dose of 420 mg/m2, PO QW (not to exceed 600 mg QW), on 
C1D1. DAY101 will be administered on Days 1, 8, 15, and 22 of a 28-day cycle. 
Individual patients will continue DAY101 using QW dosing until radiographic evidence of disease 
progression by RANO criteria (Arms 1 and 2) or RECIST v1.1 criteria (Arm 3) as determined by treating 
investigator, unacceptable toxicity, decision to enter a “drug holiday” period after completion of 26 cycles, 
patient withdrawal of consent, or death. Patients who have radiographic evidence of disease progression may 
be allowed to continue DAY101 if, in the opinion of the investigator and approved by the Sponsor, the patient 
is deriving clinical benefit from continuing study treatment. Disease assessments for patients being treated 
beyond progression should continue as per regular schedule. 
Patients may opt to enter a “drug holiday” discontinuation period at any point following 26 cycles 
(approximately two years) of therapy. Patients will continue to undergo routine periodic radiographic 
evaluations per protocol-defined timelines during the discontinuation period and may be re-treated with 
DAY101 if there is radiographic evidence of disease progression after drug discontinuation. 

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For patients requiring surgery, DAY101 should be held for six days prior to and after the surgical procedure. 
All treated patients will undergo a safety follow-up visit at 30 days after the last dose. Patients who 
discontinue therapy early will be followed for long-term survival until end of study. 
STUDY ASSESSMENTS: 
Standard monitoring for safety is outlined in the protocol and will include physical examination and 
anthropometric measurements, Karnofsky/Lansky score, clinical adverse events (AEs), laboratory variables 
(e.g., hematology and serum chemistries), ECG, ECHO/MUGA, and vital signs. 
Arms 1 and 2: Patients will undergo radiographic evaluation of their disease at the end of Cycle (C) 3 and at 
the end of every three cycles thereafter (i.e., on or up to seven days before Day >'@1 of the next cycle). 
Arm 3: Patients will undergo radiographic evaluation of their disease at the end of every second cycle, 
starting with the end of C2 (i.e., on or up to seven days before D1 of the next cycle), and at the end of every 
two cycles through 12 months of treatment. Thereafter, patients will undergo radiographic evaluation at the 
end of every three cycles. 
Blood for PK assessments will be collected as follows: 
x
C1D1 at 1, 2, and 4 hours postdose
x
C1D15 a sample between 1 and 4 hours postdose
x
C2D1 within 1 hour predose
x
C4D1 a sample between 1 and 4 hours postdose
x
For D1 of every subsequent third cycle through 13 cycles (e.g., C4D1, C7D1, C10D1, and C13D1),
a sample between 1 and 4 hours postdose
x
At time of toxicity and/or time of surgery if clinically indicated
x
At the time of a change in formulation (e.g., tablets to liquid, or vice versa), on Day 1 of the next
cycle following the formulation change: predose, 1, 2, and 4 hours postdose
In patients 2 years of age or older, Health-Related Quality of Life will be assessed using the PedsQL-Core, 
PedsQL-Cancer, and PROMIS® assessment for the patient or their parent/caregiver every third cycle. The 
PROMIS® questionnaire will only be administered to English-speaking patients enrolled in the U.S., 
Australia, and U.K. 
Central radiology review: All patients receiving protocol therapy will have their imaging scans centrally 
reviewed, in addition to review by a site or local radiologist. Copies of all eligibility, baseline, and 
on-treatment patient scans, as well as historical scans from the 12-month period immediately prior to the 
eligibility scan (if available), will be transferred to the central imaging laboratory as specified in the Imaging 
Manual. 
During the course of treatment, at the EOT, or in the event of disease progression, should patients undergo a 
tumor-directed surgery, an optional fresh tumor specimen to evaluate tumor changes that may have resulted 
from treatment will be collected. 
End of Study and Length of Study: 
The end of this study is defined as the date when the last visit occurs for the last patient enrolled. The end of 
the study is expected to occur 25 months after the last patient is enrolled into Arm 1. 
In addition, the Sponsor may decide to terminate the study at any time. 
The total length of the study, from screening of the first patient to the end of the study, is expected to be 
approximately four years. 
STATISTICAL METHODS: 
Sample Size Considerations: 
Arm 1 (Low-Grade Glioma): A sample size of 60 patients provides 88% power to reject the null ORR of 
21%, assuming that the true underlying ORR of DAY101 is 40% based on a test at the 2-sided 0.05 level. A 
result of at least 20 out of 60 (0.33) will be statistically significant. 

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Arm 2 (Low-Grade Glioma Extension): Up to approximately 60 patients may be enrolled. Arm 2 is not 
powered based on formal statistical hypothesis testing, but for practical considerations to allow patients with 
pediatric low-grade glioma to receive treatment with DAY101 after Arm 1 has fully accrued and the DSMB 
has recommended opening to enrollment. 
Arm 3 (Advanced Solid Tumor): Up to approximately 20 patients may be enrolled to provide a preliminary 
evaluation of DAY101 in pediatric patients with advanced solid tumors. For this portion of this study, a 
modified Simon 2-stage design will be used to enroll up to approximately 20 patients based on evaluation of 
ORR (confirmed PR or CR per RECIST v1.1) (Simon 1989). The statistical assumptions will require 
approximately 12 evaluable patients in the first stage and 20 evaluable patients in total. In the first stage, if 
 1 objective response (PR or CR per RECIST v1.1) is seen in the first 12 patients, the study will stop any 
further recruitment and tKHWUHDWPHQWZLOOEHFRQVLGHUHGDVQRWHIIHFWLYHLQWKLVVHWWLQJKRZHYHULI 2 
objective responses occur, an additional eight patients will be recruited. In patients with relapsed or 
progressive advanced solid tumors that have progressed after standard-of-care therapy and harbor an 
activating driver alteration, the anticipated response rate is expected to be near zero. However, for the 
purposes of sample size calculation, a null hypothesis (H0) of 5% is assumed. A sample size of 20 patients 
provides 90% power to reject the null ORR of 5%, assuming that the true underlying ORR of DAY101 is 
25% based on a test at alpha 1-sided at 0.1. A result of at least three out of 20 will be statistically significant. 
Analysis Methods: 
Efficacy Analyses 
Arm 1 (Low-Grade Glioma): The efficacy analyses will include all patients who received at least one dose 
of study drug and have measurable disease as determined by the IRC at baseline and have follow-up imaging 
or radiographically confirmed progressive disease prior to the first imaging timepoint (Arm 1 Full Analysis 
Set >)$6@). Patients who do not meet this criterion (e.g., lost to follow-up with no follow-up imaging) will be 
replaced. Some efficacy analyses may be performed with one or more tumor types combined (e.g., subgroup 
of Arm 1 FAS consisting of patients with BRAF V600 mutation vs. BRAF fusion). 
Overall response rate will be calculated by the number of patients with best overall confirmed response of CR 
or PR as determined by an IRC using the RANO criteria among the Arm 1 FAS. All responses will be 
FRQILUPHGE\DVHFRQGVFDQ 28 days after the initial response. An exact binomial test will be used to 
compare the observed response rate to the hypothesized null ORR of 21%, and a 95% confidence interval 
(CI) will be calculated using the Clopper-Pearson method.
Arm 2 (Low-Grade Glioma Extension): Where appropriate (e.g., in patients with measurable disease), 
patients will be evaluated via the same statistical methods as described for Arm 1. 
Arm 3 (Advanced Solid Tumor): The efficacy analyses will include all patients who received at least one 
dose of study drug, have measurable disease at baseline, and have follow-up imaging or radiographically 
confirmed progressive disease prior to the first imaging timepoint (Arm 3 FAS). Patients who do not meet 
this criterion (e.g., lost to follow-up with no follow-up imaging) will be replaced. These analyses may be 
summarized by tumor type, and some efficacy analyses may be performed with one or more tumor types 
combined. 
The estimate of the ORR will be calculated by the number of patients with best overall confirmed response of 
CR or PR as determined by an IRC using RECIST v1.1 criteria among the Arm 3 FAS. All responses will be 
confirmed by a second scan t 28 days after the initial response. The estimate of the ORR will be 
accompanied by 1- and 2-sided CIs with various coverage probabilities (e.g., 80%, 95%). The primary 
analysis of ORR will be based on the responses determined by an IRC. A secondary analysis will be based on 
the IRC’s assessment. 

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Safety Analyses 
A safety review committee (SRC) will be established to oversee the safety aspects of the study. The SRC 
membership will consist of the Sponsor’s Medical Monitor for this study, a Clinical Operations 
representative, and a clinically qualified representative of the Principal Investigator from each active clinical 
site contributing patients to that cohort. The SRC will meet monthly until completion of enrollment, and then 
quarterly until study closure. In addition, an independent DSMB will be established and will meet 
approximately every three months to review safety and efficacy data across the entire DAY101 program. Any 
emergent safety issue identified by the SRC will be escalated to the DSMB. 
Safety will be assessed by clinical review of all relevant parameters, including AEs, serious adverse events 
(SAEs), laboratory values, and vital signs. Unless specified otherwise, the safety analyses will be conducted 
for the safety population defined in the protocol. 
Pharmacokinetic Analyses 
Plasma concentrations of DAY101 will be determined with a validated bioanalytical assay. The following PK 
parameters may be calculated where appropriate: maximum drug concentration (Cmax), minimum drug 
concentration (Cmin), Cave, time at which maximum observed concentration occurs (Tmax,) area under the 
concentration-time curve from time zero to t (AUC0–t), and apparent oral clearance of drug (CL/F). Summary 
statistics will be generated as appropriate. 
Patient-Reported Outcomes 
Changes in quality-of-life measures from baseline will be evaluated for all patients 2 years of age or older 
using the PedsQL-Core, PedsQL-Cancer, and PROMIS® assessment. The PROMIS® questionnaire will only 
be administered to English-speaking patients enrolled in the U.S., Australia, and U.K. Longitudinal changes 
in quality-of-life scores from baseline will be summarized in a descriptive manner. 

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TABLE OF CONTENTS 
PROTOCOL AMENDMENT SUMMARY OF CHANGES ...................................... 3 
PROTOCOL SYNOPSIS ............................................................................................ 7 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS .............................. 23 
1.
INTRODUCTION .................................................................................. 26 
1.1. 
Background on Disease .......................................................................... 26 
1.1.1. 
Cancer Physiology .................................................................................. 26 
1.1.2. 
Low-Grade Gliomas ............................................................................... 27 
1.1.2.1. 
Current Therapies ................................................................................... 30 
1.1.3. 
Pediatric Solid Tumors ........................................................................... 33 
1.1.3.1. 
Role of RAF Fusions in Pediatric Solid Tumors .................................... 33 
1.2. 
Background on DAY101 ........................................................................ 34 
1.2.1. 
DAY101 Nonclinical Data ..................................................................... 34 
1.2.2. 
DAY101 Clinical Data ........................................................................... 35 
1.2.2.1. 
Clinical Pharmacokinetics ...................................................................... 36 
1.2.2.2. 
Clinical Efficacy ..................................................................................... 36 
1.2.2.3. 
Clinical Safety ........................................................................................ 37 
1.3. 
Study Rationale and Dose Justification .................................................. 39 
1.3.1. 
Study Rationale ....................................................................................... 40 
1.3.2. 
Justification for Dose .............................................................................. 41 
1.3.2.1. 
Potential Developmental Toxicities and Dosing Considerations ........... 45 
1.3.2.2. 
Drug Metabolism .................................................................................... 45 
1.3.3. 
Risk Management ................................................................................... 46 
1.3.4. 
Required Study Procedures ..................................................................... 46 
1.3.5. 
Continuous Review of Safety Data......................................................... 47 
1.3.6. 
Potential Benefit for Patients in Clinical Trials and Patients in General 47 
1.3.7. 
Integrated Benefit/Risk Assessment ....................................................... 47 
2.
STUDY OBJECTIVES .......................................................................... 48 
3.
INVESTIGATIONAL PLAN ................................................................. 53 
3.1. 
Study Design ........................................................................................... 53 
3.1.1. 
Arm 1: Low-Grade Glioma .................................................................... 55 
3.1.2. 
Arm 2: Low-Grade Glioma Extension ................................................... 55 

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3.1.3. 
Arm 3: Advanced Solid Tumor .............................................................. 56 
3.1.4. 
End of Study and Length of Study ......................................................... 56 
3.1.5. 
Number of Patients ................................................................................. 57 
3.2. 
Investigational Sites ................................................................................ 57 
4.
SELECTION OF STUDY POPULATION ............................................ 57 
4.1. 
Inclusion Criteria .................................................................................... 57 
4.2. 
Exclusion Criteria ................................................................................... 59 
5.
TREATMENT ........................................................................................ 60 
5.1. 
Investigational Product ........................................................................... 60 
5.2. 
DAY101 Administration ........................................................................ 61 
5.2.1. 
General Dosing Instructions ................................................................... 61 
5.2.2. 
Dose Modifications ................................................................................. 63 
5.2.3. 
Management of Treatment-Related Events ............................................ 64 
5.2.3.1. 
Ocular Disturbances ................................................................................ 65 
5.2.3.2. 
Photosensitivity....................................................................................... 65 
5.2.3.3. 
Rashes ..................................................................................................... 65 
5.2.3.4. 
Increased Creatine Phosphokinase ......................................................... 65 
5.2.3.5. 
Increased Liver Transaminases ............................................................... 66 
5.3. 
Prior and Concomitant Medications ....................................................... 67 
5.3.1. 
General .................................................................................................... 67 
5.3.2. 
Allowed Concomitant Medications ........................................................ 67 
5.3.3. 
Prohibited Concomitant Medications ..................................................... 68 
5.3.4. 
Concurrent Surgery ................................................................................. 68 
5.3.5. 
Palliative Radiotherapy ........................................................................... 69 
5.4. 
Removal of Patients from Therapy or Assessment................................. 69 
6.
TESTS AND EVALUATIONS .............................................................. 70 
6.1. 
Screening ................................................................................................ 70 
6.2. 
Enrollment .............................................................................................. 71 
6.3. 
Procedure Details .................................................................................... 71 
6.4. 
Medical History and Malignancy History .............................................. 71 
6.5. 
Archival Tumor ...................................................................................... 72 
6.6. 
Safety Assessments ................................................................................. 72 
6.6.1. 
Physical Examination ............................................................................. 72 

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6.6.2. 
Karnofsky or Lansky Performance Status Scales ................................... 72 
6.6.3. 
Vital Signs .............................................................................................. 72 
6.6.4. 
Ophthalmology Examination .................................................................. 72 
6.6.5. 
Dermatologic Examination ..................................................................... 73 
6.6.6. 
Neurologic Examination ......................................................................... 73 
6.6.7. 
Assessment of Change in Pubertal Development ................................... 74 
6.6.8. 
Cardiac Function ..................................................................................... 74 
6.6.8.1. 
Electrocardiograms ................................................................................. 74 
6.6.8.2. 
Echocardiogram/Multiple-Gated Acquisition ........................................ 74 
6.7. 
Laboratory Tests ..................................................................................... 74 
6.7.1. 
Pregnancy Test ........................................................................................ 74 
6.7.2. 
Hematology ............................................................................................. 75 
6.7.3. 
Serum Chemistries .................................................................................. 75 
6.7.4. 
Thyroid Function Tests ........................................................................... 75 
6.8. 
Pharmacokinetic Samples: Blood ........................................................... 75 
6.9. 
Disease Assessment ................................................................................ 76 
6.9.1. 
Tumor Measurements ............................................................................. 76 
6.9.1.1. 
Collection of Radiographic Studies for Independent Review ................ 76 
6.9.1.2. 
Visual Acuity Assessments..................................................................... 76 
6.9.1.3. 
Motor Function Evaluation Using the Vineland Motor Scale ................ 77 
6.9.2. 
Quality of Life: Pediatric Quality of Life Inventory—Core, Cancer, and 
Patient-Reported Outcomes Measurement Information System ............ 77 
6.10. 
Telephone/Telemedicine Visit ................................................................ 78 
6.11. 
Survival Status ........................................................................................ 78 
6.12. 
Study Drug Administration and Dosing Diary ....................................... 78 
6.13. 
Concomitant Medication ........................................................................ 79 
6.14. 
End of Treatment Visit ........................................................................... 79 
6.15. 
Safety Follow-Up Visit ........................................................................... 79 
6.16. 
Long-Term Follow-Up ........................................................................... 79 
6.17. 
Force Majeure Flexibility ....................................................................... 79 
7.
PLANNED ANALYSES ........................................................................ 80 
7.1. 
Analysis Populations .............................................................................. 80 
7.2. 
Determination of Sample Size ................................................................ 81 

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7.3. 
Statistical Methods .................................................................................. 82 
7.3.1. 
Efficacy Analyses ................................................................................... 82 
7.3.1.1. 
Arm 1: Low-Grade Glioma .................................................................... 82 
7.3.1.2. 
Arm 2: Low-Grade Glioma Extension ................................................... 83 
7.3.1.3. 
Arm 3: Advanced Solid Tumor .............................................................. 83 
7.3.2. 
Safety Analyses ...................................................................................... 84 
7.3.2.1. 
Deaths ..................................................................................................... 85 
7.3.2.2. 
Laboratory Values .................................................................................. 85 
7.3.2.3. 
Vital Signs .............................................................................................. 85 
7.3.2.4. 
Concentration QTc (cQTc) Analysis ...................................................... 85 
7.3.2.5. 
Concomitant Medications ....................................................................... 85 
7.3.2.6. 
Pharmacokinetic Analyses ...................................................................... 85 
7.3.3. 
Health-Related Quality of Life ............................................................... 86 
7.3.4. 
Visual Acuity Outcomes ......................................................................... 86 
7.3.5. 
Motor Function (Vineland) Outcomes .................................................... 86 
8.
SAFETY ................................................................................................. 86 
8.1. 
Adverse Events and Serious Adverse Events ......................................... 86 
8.1.1. 
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information ..................................................................... 86 
8.1.2. 
Method of Detecting Adverse Events and Serious Adverse Events ....... 87 
8.1.3. 
Follow-Up of Adverse Events and Serious Adverse Events .................. 87 
8.1.4. 
Regulatory Reporting Requirements for Serious Adverse Events ......... 87 
8.1.5. 
Pregnancy ............................................................................................... 88 
8.1.6. 
Deaths ..................................................................................................... 88 
8.2. 
Safety Review Committee and Data Safety Monitoring Board.............. 89 
8.3. 
Stopping Rules ........................................................................................ 89 
8.4. 
Criteria for Pausing or Stopping the Study ............................................. 89 
8.5. 
Grading and Intensity of Adverse Events ............................................... 90 
8.6. 
Relationship to Study Drug .................................................................... 90 
8.7. 
Serious Adverse Event Follow-Up ......................................................... 91 
9.
STUDY ADMINISTRATION ............................................................... 91 
9.1. 
Regulatory and Ethical Considerations .................................................. 91 
9.1.1. 
Regulatory Authority Approval .............................................................. 91 

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9.1.2. 
Ethics Approval ...................................................................................... 91 
9.1.3. 
Patient Informed Consent and Pediatric Assent ..................................... 92 
9.1.4. 
Investigator Reporting Requirements ..................................................... 93 
9.2. 
Data Management ................................................................................... 93 
9.3. 
Study Monitoring .................................................................................... 93 
9.4. 
Termination ............................................................................................. 94 
9.5. 
Records Retention ................................................................................... 94 
9.6. 
Confidentiality of Information ................................................................ 94 
10.
REFERENCES ....................................................................................... 95 
LIST OF TABLES 
Table 1: 
Histological Subgroups of Low-Grade Gliomas Demonstrating in Which 
Tumors RAF Alterations Have Been Identified ..................................... 30 
Table 4: 
Arm 1 (Low-Grade Glioma) Objectives and Endpoints ......................... 48 
Table 5: 
Arm 2 (Low-Grade Glioma Extension) Objectives and Endpoints ........ 50 
Table 6: 
Arm 3 (Advanced Solid Tumor) Objectives and Endpoints ................... 52 
Table 7: 
Dose Rounding Guidelines for DAY101 Tablets (100 mg) ................... 62 
Table 8: 
Dose and Volume Rounding Guidelines for DAY101 Reconstituted 
Liquid Suspension (25 mg/mL) .............................................................. 63 
Table 9: 
Treatment-Emergent Adverse Events Requiring Dose Interruption Until 
5HVROXWLRQWR*UDGHRU%DVHOLQH ....................................................... 64 
Table 10: Increased Creatine Phosphokinase Recommendations ........................... 66 
Table 11: Increased Liver Transaminases Recommendations ................................ 67 
Table 12: Schedule of Blood Sample Collections for DAY101 Pharmacokinetics 75 
Table 13: Population Definitions ............................................................................ 81 
Table 14: Summary of Adverse Event Collection Periods ..................................... 87 
Table 15: NCI CTCAE Definitions of Severity for Adverse Reactions ................. 90 
Table 16: Arms 1 and 2 Schedule of Assessments ............................................... 101 
Table 17: Arm 3 Schedule of Assessments........................................................... 107 
Table 18: .DUQRIVN\3HUIRUPDQFH6FRUH\HDUVROG ................................... 113 
Table 19: Lansky Performance Score (< 16 years old)......................................... 113 

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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation or Term 
Definition 
AE 
adverse event 
ALT 
alanine aminotransferase 
ASCO 
American Society for Clinical Oncology 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
AUC0–t 
area under the concentration-time curve from time zero to t 
AUC0– 
area under the concentration-time curve from time zero to infinity 
AUClast 
area under the concentration-time curve from time zero to the last timepoint 
BCRP 
breast cancer resistance protein 
BCVA 
best corrected visual acuity 
BOR 
best overall response 
BP 
blood pressure 
BRAF 
v-raf murine sarcoma viral oncogene homolog B
BSA 
body surface area 
C 
Cycle 
CI 
confidence interval 
CL/F 
apparent oral clearance of drug 
CLIA 
Clinical Laboratory Improvement Amendments 
Cmax 
maximum drug concentration 
Cmin 
minimum drug concentration 
CNS 
central nervous system 
CPK 
creatine phosphokinase 
CR 
complete response 
CRF 
case report form 
CSR 
central serous retinopathy 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
CYP2C8 
cytochrome P450 2C8 
CYP3A4 
cytochrome P450 3A4 
D 
Day 
DLT 
dose-limiting toxicity 
DOR 
duration of response 
DRESS 
drug reaction with eosinophilia and systemic symptoms 
DSMB 
Data Safety Monitoring Board 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ECHO 
echocardiogram 

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Abbreviation or Term 
Definition 
EDC 
electronic data capture 
EMA 
European Medicines Agency 
EOT 
end of treatment 
ERK 
extracellular signal-related kinase 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FAS 
Full Analysis Set 
FFPE 
formalin-fixed, paraffin-embedded 
GCP 
Good Clinical Practices 
H0 
null hypothesis 
HREC 
Human Research Ethics Board 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IFS 
infantile fibrosarcoma 
IRB 
Institutional Review Board 
IRC 
independent radiology review committee 
IRT 
interactive response technology 
ITT 
intent to treat 
LVEF 
left ventricular ejection fraction 
MAPK 
mitogen-activated protein kinase 
MedDRA 
Medical Dictionary for Regulatory Activities 
MEK 
mitogen-activated protein kinase 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
MUGA 
Multiple-gated acquisition 
NCI 
National Cancer Institute 
NE 
not evaluable 
NTRK genes 
neurotrophic tyrosine kinase receptor genes 
OPG 
optic pathway glioma 
ORR 
overall response rate 
OS 
overall survival 
PD 
progressive disease 
PedsQL-Core 
Pediatrics Quality of Life™—Core 
PedsQL-Cancer 
Pediatrics Quality of Life™—Cancer 
pERK 
phosphorylated ERK 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 

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Abbreviation or Term 
Definition 
PO 
per os, orally 
PR 
partial response 
PROMIS® 
Patient-Reported Outcomes Measurement Information System 
PXA 
xanthoastrocytoma 
Q2D 
every other day 
QOL 
quality of life 
QTc 
QT interval corrected for heart rate 
QTcF 
QT interval corrected for heart rate by Fridericia's formula 
ǻ47F) 
change in QT interval corrected for heart rate by Fridericia's formula 
QW 
once weekly 
RANO 
Response Assessment in Neuro-Oncology 
RAPNO 
Response Assessment in Pediatric Neuro-Oncology 
REB 
Research Ethics Board 
RP2D 
recommended Phase 2 dose 
RVO 
retinal vein occlusion 
SAE 
serious adverse event 
SCC 
squamous cell carcinoma 
SD 
stable disease 
SGOT 
serum glutamic-oxaloacetic transaminase 
SGPT 
serum glutamic-pyruvic transaminase 
SJS 
Stevens Johnsons syndrome 
SRC 
Safety Review Committee 
T3 
triiodothyronine 
T4 
tetraiodothyronine 
t1/2 
half-life 
TAC 
Teller Acuity Cards® 
TEAE 
treatment-emergent adverse event 
Tmax 
time at which maximum observed concentration occurs 
TNM 
tumor, node, metastasis 
TPCV 
thioguanine, procarbazine, lomustine, and vincristine 
TSH 
thyroid stimulating hormone 
TTR 
time to response 
ULN 
upper limit of normal 
VA 
visual acuity 
WHO 
World Health Organization 
XRT 
radiation therapy 

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1.
INTRODUCTION
DAY101 is an oral, selective, small-molecule, Type II pan-RAF kinase inhibitor that is being 
developed by DOT Therapeutics-1 Inc. (Day One, the Sponsor) for the treatment of recurrent 
or progressive pediatric low-grade gliomas and pediatric and adult solid tumors which harbor 
a known or expected to be activating RAF alteration. 
1.1. 
Background on Disease 
1.1.1. 
Cancer Physiology 
The mitogen-activated protein kinase (MAPK) signaling pathway is an essential pathway that 
regulates key cell functions, such as growth, survival, and differentiation. Genomic 
alterations and dysregulation of the MAPK pathway have been described in many different 
types of malignancies, including pediatric low-grade glioma (Yaeger and Corcoran 2019). 
One of the most frequently altered genes in this pathway is v-raf murine sarcoma viral 
oncogene homolog B (BRAF), in which 90% of the mutations consist of the BRAF V600E 
point mutation. This point mutation leads to both increased BRAF kinase activity that is 
independent of extracellular stimuli or RAS-GTP, and constitutive signaling that drives cell 
proliferation and tumor growth (Davies et al. 2002). Currently, the US Food and Drug 
Administration (FDA) has approved three agents that inhibit BRAF-V600E/K mutations: 
vemurafenib, dabrafenib, and encorafenib. 
Beyond point mutations, BRAF fusions and in-frame deletions have also been reported in 
human cancers (Ross et al. 2016). BRAF fusions are rearrangements in which the N-terminal 
inhibitory domain of BRAF is replaced with a different sequence that enables BRAF to 
signal as a dimer independent of RAS activation. This drives aberrant expression and 
constitutive activation of the kinase and downstream signaling pathways. Fusions involving 
oncogenes have historically been targetable by kinase inhibitors, and multiple targeted agents 
that have demonstrated clinical responses to cancer patients harboring fusions involving 
ABL, ALK, TRK, RET, and ROS1 have been approved by the US FDA and European 
Medicines Agency (EMA). 
In 2008, several research groups published critical discoveries from tumor specimens 
obtained from patients with pediatric low-grade glioma that identified a fusion involving two 
genes, KIAA1549 and BRAF, that led to constitutive activation of BRAF kinase activity, as 
well as increased expression of the fusion (see Figure 1). The identification of this 
KIAA1549:BRAF fusion led to deeper understanding of the genomic events driving growth 
of pediatric low-grade glioma (Jones et al. 2008; Penman et al. 2015). The KIAA1549:BRAF 
fusion has been found to drive the majority of pediatric low-grade gliomas, and exhibits 
kinase activity and constitutive downstream signaling comparable to the canonical BRAF 
V600E point mutation (Jones et al. 2008). The KIAA1549:BRAF fusion is found in 30% to 
40% of pediatric low-grade gliomas at the population level, and 70% to 80% of pilocytic 
astrocytomas (Ryall et al. 2020); the BRAF V600E point mutation is less common in 

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can result in multiple endocrine dysfunctions, particularly in the pituitary gland, significantly 
impacting growth and development of the child. In infants, a diencephalic syndrome causes 
severe emaciation with high risk of fatal outcome. Treatment of pediatric low-grade gliomas 
with chemotherapy can result in both acute and chronic toxicities, depending on the treatment 
regimen and duration. This includes bone marrow toxicity in up to 100% of treated children, 
allergic reactions, impaired renal function, impaired hearing, and neurotoxicity. Radiation 
therapy can result in cerebrovascular disease and long-term neurocognitive deficits, 
particularly in younger patients, as well as increased risk of secondary malignancies. It is 
increasingly well established that patients, especially long-term survivors, have significant 
adverse outcomes related to the location and growth of the tumor (Sievert et al. 2009). 
Cerebral hemisphere location, younger age at diagnosis, and hydrocephalus requiring a shunt 
have all been found to be significant predictors of lower cognitive performance on IQ scales. 
Children with infratentorial tumors can have significant language, cognitive, behavioral, and 
social dysfunctions. A combined analysis of Children’s Cancer Group (CCG-9891) and 
Pediatric Oncology Group (POG-9130) data of 103 children with low-grade cerebellar 
astrocytomas treated with surgery alone revealed an elevated risk of cognitive and 
adaptive-behavioral impairment that was not associated with complications of the tumor or 
surgery (Beebe et al. 2005). Similar deficits were ubiquitous in children with extracerebellar 
tumors treated with surgery alone (Ris et al. 2008). 
As noted above, multiple large-scale sequencing efforts of pediatric tumors have led to a 
better biological understanding of the molecular underpinnings of these tumors. The 
KIAA1549:BRAF fusion was found in the majority of tissue samples from patients with 
pilocytic astrocytomas (Jones et al. 2008). Over time, additional RAF genomic alterations, 
including the BRAF V600E mutation and both BRAF and CRAF/RAF1 fusions with novel 
partners, have been identified in patients with low-grade gliomas, cementing the idea of RAF 
as an oncogenic driver in low-grade glioma, just as an NTRK fusion is the key oncogenic 
event in patients with infantile fibrosarcoma (IFS) (Knezevich et al. 1998). 
Pilocytic astrocytomas (Grade I) and diffuse fibrillary astrocytomas (Grade II) are the two 
most common pediatric low-grade gliomas. Pilocytic astrocytomas commonly occur in 
children up to 14 years of age. They can occur anywhere in the CNS, although they are 
typically located in the cerebellum, hypothalamus/optic nerve pathway, dorsally exophytic 
brain stem, or spinal cord. Conversely, diffuse fibrillary astrocytomas rarely occur before the 
age of 20 years and are located in the supratentorial region, deep midline structures, or 
cervicomedullary region of the brain stem (Waanders et al. 2016). Pilomyxoid astrocytomas 
(Grade II) are a subset of pilocytic tumors with a more aggressive clinical course. These 
occur in the hypothalamus in patients with a median age of 21 months. The Grade II tumor 
pleomorphic xanthoastrocytoma (PXA) is less aggressive than the diffuse fibrillary 
astrocytoma and more similar to the pilocytic astrocytoma. Gangliogliomas (Grade II), 
subependymal giant cell astrocytomas, and oligodendrogliomas are also included in the 
low-grade glioma classification (Waanders et al. 2016). The subtypes and prognosis of 

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Table 1: 
Histological Subgroups of Low-Grade Gliomas Demonstrating in Which 
Tumors RAF Alterations Have Been Identified 
Histological 
Subgroup 
WHO 
Grade 
KIAA1549: 
BRAF 
Fusion 
Described 
Average % 
Fusion- 
Positive 
Patients 
Other RAF 
Fusions 
BRAF 
V600E 
Described 
Average % 
BRAF 
V600E-
Positive 
Patients 
Pilocytic 
astrocytoma 
I 
Yes 
77.2 
FAM131B:BRAF 
SRGAP3:RAF1 
QK1:RAF1 
Yes 
6.2 
Pilomyxoid 
astrocytoma 
II 
Yes 
62.5 
Yes 
5.0 
Diffuse fibrillary 
astrocytoma 
II 
Yes 
3.0 
FAM131B:BRAF 
Yes 
8.1 
Pleomorphic 
xanthoastrocytoma 
II 
Yes 
55.6 
N/A 
Yes 
50.8 
Dysembryoplastic 
neuroepithelial 
tumor 
I 
No 
N/A 
N/A 
No 
N/A 
Desmoplastic 
infantile 
astrocytoma/glioma 
II 
No 
N/A 
FXR1:BRAF 
Yes 
8.5 
Abbreviations: BRAF, v-raf murine sarcoma viral oncogene homolog B; FAM131B, family with sequence 
similarity 131 member B; FXR1, FMR1 autosomal homolog 1; N/A, not applicable; SRGAP3, SLIT-ROBO 
Rho GTPase activating protein 3; WHO, World Health Organization. 
Adapted from Penman et al. 2015. 
1.1.2.1. 
Current Therapies 
The mainstays of treatment with pediatric low-grade gliomas have historically been surgery, 
radiation, and multiagent chemotherapy. While surgical resection of pediatric low-grade 
gliomas is associated with 10-year overall survival (OS) rates of 90% or more, the majority 
of children are unable to undergo complete resection. In addition, depending on the location 
of the tumor, surgical resection can be associated with significant and long-lasting morbidity. 
Incompletely resected or unresectable pediatric low-grade gliomas have a high rate of disease 
progression or recurrence. Patients with subtotal resections have a 10-year progression-free 
survival (PFS) of 55% (Tihan et al. 2012). Historically, focal radiation therapy was believed 
to lead to an improvement in 10-year PFS, with results in the 60% to 65% range. However, 
more recent studies have questioned the role of radiotherapy compared with chemotherapy or 
observation alone. Whole-brain radiotherapy has been shown to adversely affect IQ in 
survivors of pediatric brain tumors, as well as cause a number of other neurocognitive effects 
(Waanders et al. 2016), along with increased risk of cerebral vasculopathy and stroke. 
Chemotherapy has been the mainstay of treatment options for patients with progressive 
low-grade glioma, with vincristine and carboplatin, single-agent vinblastine, or thioguanine, 

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procarbazine, lomustine, and vincristine (TPCV) being the most widely used combinations. 
The current standard-of-care front-line chemotherapeutic regimen (vincristine/carboplatin) 
has limited efficacy, and the long-term burden of both the disease- and treatment-related 
morbidity is significant. Results from the largest randomized Phase 3 study to date for 
children with newly diagnosed pediatric low-grade glioma showed a five-year event-free 
survival of only 47% for vincristine/carboplatin (Ater et al. 2012). Of note, the overall 
response rate (ORR) (complete response [CR@ + partial response [PR@) to chemotherapy in 
newly diagnosed pediatric low-grade glioma was noted to be 35% for vincristine/carboplatin 
(33/93 patients; 95% confidence interval [CI@: 27, 46) and 30% for TPCV (31/103 patients; 
95% CI: 22, 40). Patients whose tumors progressed following the failure of these 
combinations have few treatment options. The largest study of chemotherapy in this 
population was performed with single-agent vinblastine, which resulted in an ORR (CR + 
PR) of 21% (11/51 patients), and a five-year PFS of 42.3% ± 7.2% (Bouffet et al. 2012). At 
present, there is no consensus on treatment options for patients who have relapsed, refractory, 
progressive, or disseminate low-grade glioma (Waanders et al. 2016), and no targeted 
therapeutics have been approved for this patient population. 
Currently, the FDA and EMA have approved three agents that specifically inhibit 
BRAF V600E (vemurafenib, dabrafenib, encorafenib). All three of these Type I RAF 
inhibitors exert their effect only on the BRAF V600 mutation and they do not address the 
KIAA1549:BRAF fusions endemic in pediatric low-grade gliomas. Moreover, in the 
presence of monomeric mutant BRAF, the mechanism of binding of these inhibitors is such 
that it results in the induced dimerization and paradoxical activation of wild-type RAF 
proteins in nontumor tissue. This leads to a common adverse event (AE) associated with 
these agents, the development of proliferative premalignant and malignant skin lesions 
(e.g., keratoacanthomas and squamous cell carcinomas). In addition, Type I agents are not 
able to bind to the RAF kinase domains in KIAA1549:BRAF fusions, and are thus unable to 
effectively inhibit the hyperactive extracellular signal-related kinase (ERK) signaling that 
results from this fusion. 
Importantly, Type I RAF inhibitors have been shown to result in paradoxical activation of 
pediatric low-grade glioma models driven by the KIAA1549:BRAF fusion and to accelerate 
the growth of tumor models driven by the KIAA1549:BRAF fusion. Clinical 
proof-of-concept for this phenomenon occurred in 2014 when the multikinase inhibitor 
sorafenib, which blocks BRAF V600 mutations in a manner similar to other Type I 
inhibitors, was studied in children with pediatric low-grade gliomas and produced 
unexpected and unprecedented acceleration in tumor growth. This effect was later found to 
be related to paradoxical ERK activation (Karajannis et al. 2014). As such, the Type I RAF 
inhibitors are considered to be contraindicated in the large percentage of patients with 
pediatric low-grade glioma without a BRAF V600E activating mutation. Although the 
currently available Type I BRAF inhibitors are being studied in children with BRAF V600 
mutated low-grade gliomas, and potentially being used off-label in this patient population, 

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this is thought to be an inferior treatment option with only transient tumor control, as well as 
the safety issues commonly seen across the class of Type I RAF inhibitors. 
Mitogen-activated protein kinase (MEK) inhibitors have been studied in pediatric low-grade 
glioma because of their ability to inhibit downstream signaling from BRAF V600E and 
KIAA1549:BRAF fusion. For example, selumetinib has been shown to cause tumor 
regression and disease stabilization (Fangusaro et al. 2019) without paradoxical activation. 
The largest study to date of selumetinib in recurrent, refractory, or progressive pediatric 
low-grade glioma patients with a BRAF alteration (n = 25) reported nine patients (36% [95% 
CI 18–@ZLWK a sustained partial response. The most frequent Grade 3 or greater AEs in 
this study were elevated creatine phosphokinase (CPK) (10%) and maculopapular rash 
(10%). It is important to note that available MEK inhibitors do not directly target the driver 
mutations, are not CNS penetrant, and are also not approved for the treatment of 
relapsed/refractory pediatric low-grade glioma. 
With regard to vemurafenib, there are two published datasets. Initially, a retrospective chart 
review of patients with BRAF V600E-positive low-grade glioma treated off-label with 
vemurafenib (Del Bufalo et al., 2018) reported one CR, three PRs, and one patient with 
stable disease (SD). More recently, the Phase 1 portion of a prospective Phase 1/2 study was 
published, which established the adult recommended Phase 2 dose as the pediatric 
recommended Phase 2 dose. The objective response rate in the Phase 1 portion was found to 
be 32%. Centrally reviewed best radiographic responses included one CR, five PRs, and 13 
patients with SD (Nicolaides et al., 2020). Vemurafenib was well tolerated with a similar 
safety profile to what has been seen in adults. The most common treatment-related Grade 3 
or greater AEs in this study were secondary keratoacanthoma (n = 1); rash (n =16); and fever 
(n = 5). 
The Type I RAF inhibitor dabrafenib has been investigated in pediatric patients with BRAF 
V600 mutant low-grade glioma (Hargrave et al., 2019). Thirty-two patients ranging in age 
from 2 to 17 years with locally determined BRAF V600 mutation–positive refractory or 
recurrent low-grade glioma were treated. Independent radiological review utilizing the 
Response Assessment in Neuro-Oncology (RANO) criteria confirmed an objective response 
rate of 44% (14/32, CI 26-62) which included one CR and 13 PRs. Eleven patients with SD 
had significant tumor responses. Therapy was well tolerated with the most common 
treatment-related AEs being fatigue (34%), rash (31%), dry skin (28%), pyrexia (28%), and 
maculopapular rash (28%) (Hargrave et al., 2019). 
Finally, data generated from ongoing studies of various MAPK pathway inhibitors in patients 
with low-grade gliomas have shown that responses in pediatric low-grade gliomas driven by 
either BRAF V600 mutations (treated with Type I RAF inhibitors and MEK inhibitors) or 
KIAA1549:BRAF fusions (treated with MEK inhibitors) are often durable for only as long as 
drug can be administered. Thus, specificity of targeting and tolerability over a long course of 
treatment are key determinants of duration of response (DOR), and therefore of clinical 
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Because of the natural history of pediatric low-grade gliomas, the goals of therapy for 
patients with relapsed or progressive pediatric low-grade glioma are a reduction of the 
burden of tumor, the prevention of continued growth, and avoidance of the short- and 
long-term toxicities associated with subsequent need for surgery, radiation therapy, or 
additional cytotoxic chemotherapy between the time of recurrence or progression and 
senescence. Although these tumors, and the associated treatment, are a significant source of 
morbidity in the developing child, if these children survive into young adulthood, many of 
these tumors undergo senescence (Jacob et al. 2011). 
1.1.3. 
Pediatric Solid Tumors 
Globally, approximately 400,000 children and adolescents aged 0 to 19 years are diagnosed 
with cancer each year (Steliarova-Foucher et al. 2017). The most common of these are acute 
lymphoblastic leukemia, brain and other CNS tumors, neuroblastoma, lymphoma, and 
thyroid cancer. Patients who respond to intensive treatment regimens and ultimately survive 
their disease face long-term morbidity and the risk of early mortality as a result of their 
treatment (Armstrong et al. 2010, Yeh et al. 2010, Kirchoff et al. 2010, Mitby et al. 2003, 
Pui et al. 2003). Although 5-, 10-, and 15-year disease-related mortality has improved in 
recent decades with better therapies and supportive care, many patients still relapse and 
eventually succumb to their disease. Currently, treatment for advanced cancers is typically 
histology based and varies across tumor types, most often including combination 
chemotherapy and/or immunotherapy. 
The application of next-generation sequencing approaches to a large collection of human 
tumors has led to the identification of activating alterations in the BRAF or CRAF (also 
known as RAF1) gene, including fusions and mutations, in a fraction of other tumor types, 
including embryonal sarcomas, melanoma, thyroid cancers, and Langerhans histiocytosis 
(Coffin et al. 2020, Penning et al. 2021, Rankin et al. 2021). Currently, a number of these 
patients receive chemotherapy and/or undergo amputations or other disfiguring surgery as 
standard of care. 
To improve efficacy and reduce toxicity, molecularly targeted therapies present an attractive 
approach. As described in Section 1.1.1, multiple targeted agents that have demonstrated 
clinical responses to patients with cancer harboring fusions involving ABL, ALK, TRK, 
RET, and ROS1 have been approved by the US FDA and EMA. However, despite the 
availability of these agents, there have been few successful applications for solid tumors in 
pediatric populations (Bellantoni et al. 2021). 
1.1.3.1. 
Role of RAF Fusions in Pediatric Solid Tumors 
In pediatric populations, solid tumors with an activating fusion in the BRAF or CRAF/RAF1 
(collectively referred to as RAF) gene occur infrequently, but data continue to emerge 
indicating a diverse landscape of cancer types that harbor these alterations 
(Coffin et al. 2020, Penning et al. 2021, Rankin et al. 2021). The application of 
next-generation sequencing in larger datasets is contributing to an increased understanding of 
these tumors. In one recently published work of comprehensive genomic profiling 

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representing 3633 pediatric tumors, 221 (6.1%) of samples were found to harbor BRAF 
alterations likely to represent driver events. Forty-five of those samples represented solid 
tumors or hematologic malignancies and included known activating BRAF fusions such as 
KIAA1549:BRAF in embryonal rhabdomyosarcoma and sarcoma (not otherwise specified 
[NOS@), CUX1-BRAF in sarcoma (NOS), STAR-D3NL-BRAF in sarcoma (NOS), 
PPP1CC-BRAF in acinar cell carcinoma, and KHDRBS2-BRAF in large cell neuroendocrine 
carcinoma (Rankin et al. 2021). Activating BRAF fusions and mutations have recently been 
reported in mesenchymal tumors with IFS-like morphology (Coffin et al. 2020, Penning et al. 
2021). Beyond activating BRAF fusions, activating CRAF/RAF1 fusions have also been 
detected in melanoma and low-grade glioma. These can also constitutively activate the 
MAPK pathway (Williams et al. 2020, Rankin et al. 2021, Wright et al. 2020). Importantly, 
few co-occurring genomic driver alterations were identified (Rankin et al. 2021). 
As demonstrated in the Rankin, Coffin, Penning, Drilon, and Stransky works, oncogenic 
fusions normally occur in isolation from other driver mutations. This leads to the hypothesis 
that an activating RAF fusion of the BRAF or CRAF/RAF1 gene is the likely oncogenic 
alteration in these tumors. As with other known oncogenic drivers such as ALK, ROS-1, 
RET, and TRK, these solid tumors are amenable to monotherapy treatment, which can result 
in profound tumor shrinkage. DAY101, a pan-RAF inhibitor that has been shown to inhibit 
both BRAF and CRAF/RAF1 fusions (Sun et al. 2017, Wright et al. 2020), may provide 
clinical benefit from a molecularly targeted approach in pediatric patients whose tumors have 
progressed after standard of care therapy. Chemotherapy has a less than favorable side effect 
and long-term sequelae profile in a pediatric patient population, commonly leading to 
negative long-term outcomes. 
Therefore, there is an urgent need to identify new targeted therapies that potently inhibit 
activating RAF fusions in tumors while sparing other kinase and non-kinase off-targets that 
contribute to significant toxicity. A significant number of patients with advanced cancers 
harboring a BRAF or CRAF/RAF1 fusion could benefit from potent and selective RAF 
kinase inhibition. 
1.2. 
Background on DAY101 
1.2.1. 
DAY101 Nonclinical Data 
A comprehensive package of nonclinical studies has been conducted with DAY101 and 
provides a thorough pharmacological and toxicological profile of DAY101 in multiple 
species, as detailed in the Investigator’s Brochure (IB). 
DAY101 has been extensively studied in both in vitro and in vivo systems and has been 
found to result in potent inhibition of oncogenic BRAF V600E mutations 
(Olszanski et al. 2017). In contrast to the approved Type I RAF inhibitors (e.g., vemurafenib, 
dabrafenib, encorafenib), DAY101 inhibits both wild-type BRAF and CRAF/RAF1 kinases 
and, importantly, hyperactivated signaling resulting from BRAF fusions, including the 
KIAA1549:BRAF fusion (Sun et al. 2017). In vitro studies have demonstrated that DAY101 

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inhibits phosphorylated ERK (pERK) signaling, along with cell proliferation, in a wide array 
of cell lines with high MAPK activity. In vivo studies have shown that pERK is suppressed 
in xenograft tumor models harboring mutant BRAF, wild-type BRAF, or KIAA1549:BRAF 
fusions. Xenograft models also demonstrated antitumor activity resulting from monotherapy 
treatment with DAY101. 
DAY101 has been shown to inhibit the kinase activity of BRAF in the context of BRAF 
kinase domain fusions with various 5މ gene partners, most notably fusion with the KIAA1549 
gene. KIAA1549:BRAF fusion kinase activity is inhibited by DAY101 with comparable 
potency to inhibition of BRAF V600E in cell model systems, without the paradoxical 
activation of the MAPK pathway reported for Type I BRAF inhibitors (Sun et al. 2017). 
Importantly, in contrast to Type I RAF inhibitors, DAY101 does not result in paradoxical 
activation of MAPK signaling in BRAF wild-type tissues (Sun et al. 2017), which limits the 
use of Type I inhibitors. In contrast to MEK inhibitors, DAY101 directly inhibits BRAF 
dimers, blocking downstream pERK signaling. As detailed below, the profile of DAY101 
does not appear to have the severe dermatologic, cardiac, or ophthalmologic liabilities of the 
incumbent RAF or MEK inhibitors. Finally, as opposed to all approved MEK and BRAF 
inhibitors, DAY101 has significantly greater CNS penetration (Sun et al. 2017). 
1.2.2. 
DAY101 Clinical Data 
Two clinical studies (C28001 and C28002) in adult patients with advanced solid tumors were 
completed by the previous Sponsor. In addition, one investigator-initiated clinical study 
(PNOC014) is ongoing with DAY101 in pediatric patients with relapsed/refractory pediatric 
low-grade glioma.
Study C28001 was a Phase 1 first-in-human study conducted in adult patients with advanced 
solid tumors. DAY101 was administered orally (PO) once every other day (Q2D) in 22- and 
28-day treatment cycles, at doses of 20, 40, 80, 135, 200, and 280 mg. DAY101 was also
administered once weekly (QW) in 28-day treatment cycles with a starting dose of 400 mg,
then 600 and 800 mg. The adult maximum tolerated doses (MTDs) were reached at 200 mg
Q2D and 600 mg QW. Expansion cohorts included patients with advanced, metastatic, or
unresectable melanoma with MAPK alterations. Details of this study can be found in the
DAY101 IB.
Study C28002 was a Phase 1b study conducted in patients with advanced solid tumors who 
had failed standard therapies. This study was conducted as an “umbrella study” in which 
DAY101 was studied in combination with various chemotherapy agents or targeted therapies 
in adult patients with either advanced colorectal cancer or advanced non–small cell lung 
cancer (with either KRAS exon 2 mutations or non-V600 BRAF mutations). Details of this 
study can be found in the DAY101 IB. 

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Study PNOC014 is an investigator-initiated, Phase 1, dose-escalation study in patients aged 
1 to < 25 years with radiographically confirmed recurrent or progressive nonhematologic 
malignancies (solid tumors or primary CNS disease) with a genomic alteration resulting in 
the activation of the RAS/RAF/MEK/ERK pathway, excluding patients with NF1 
loss-of-function. Part A of this ongoing study was a dose escalation that used a 3+3 design. 
DAY101 was administered as an oral tablet with a starting dose of 280 mg/m2 (80% of the 
adult recommended Phase GRVH>53'@RI mg PO QW, adjusted for body surface area 
>%6$@ 
1.2.2.1. 
Clinical Pharmacokinetics 
Details of the PK from Studies C28001, 
, and 
 are included in 
Section 1.3.2, as well as in the IB. 
1.2.2.2. 
Clinical Efficacy 
Study C28001 
Preliminary antitumor activity was most evident in the BRAF mutation–positive, 
treatment-naive RP2D expansion melanoma cohort (ORR: 8/16 patients, 50% [95% CI: 25, 
@PHGLDQ'25>35LQ8 SDWLHQWV@ PRQWKV>&,QRWHVWLPDEOH@PHGLDQ3)6
5.7 PRQWKV>&,@$35ZDVDOVRUHSRUWHGLQ1 of 6 patients in the BRAF 
mutation–positive previously treated cohort (ORR: 17%; 95% CI: < 1, 64). 
Further details of the efficacy data from C28001 can be found in the DAY101 IB. 

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1.2.2.3. 
Clinical Safety 
Study C28001 
Takeda Study C28001 was a Phase 1, multicenter, nonrandomized, open-label, FIH clinical 
study designed to evaluate the safety, tolerability, PK, pharmacodynamics, and antitumor 
activity of oral DAY101 in adult patients with advanced solid tumors (excluding lymphoma). 
The study was composed of two phases (dose-escalation and dose-expansion phases) and 
evaluated two dosing schedules (Q2D and QW). Patients in the dose-escalation phase were 
not selected based on BRAF status. The dose-expansion phase evaluated multiple cohorts of 
patients with melanoma, including patients who were BRAF mutation–positive (including 
cohorts of those who had, and those who had not, received a prior RAF or MEK inhibitor), 
NRAS mutation–positive (including cohorts of those who had, and those who had not, 
received a prior RAF or MEK inhibitor), and BRAF/NRAS mutation–negative patients 
(including cohorts who either had or had not received a prior immune checkpoint inhibitor). 
Over the life of this study, which was completed on 16 October 2018, 110 patients were 
administered at least one dose of DAY101 on a Q2D dose schedule (30 in the dose-escalation 
phase and 80 in the dose-expansion phase). Thirty-nine patients were administered at least 
one dose of DAY101 on a QW dose schedule (20 in the QW dose-escalation phase [three in 
the 400-mg cohort, 13 in the 600-mg cohort, and four in the 800-PJFRKRUW@DQGGRVHGDW
600 mg QW in the expansion phase). 
Of the 149 patients treated, all had at least one treatment-emergent adverse event (TEAE). 
The most frequently reported TEAEs across all dose cohorts in the Q2D dose-escalation 
phase included fatigue (67%), maculopapular rash (37%), and arthralgia and constipation 
(30% each). The most frequently reported TEAEs in the Q2D dose-expansion phase included 
fatigue (43%), anemia (41%), constipation and maculopapular rash (38% each), nausea 
(36%), and dyspnea (30%). 
The most frequently reported TEAEs across all dose cohorts in the QW dose-escalation 
phase included fatigue (55%), anemia (40%), nausea (35%), and headache (30%). In the QW 
dose-expansion cohort, the most frequently reported TEAE was fatigue (47%). More details 
can be found in the DAY101 IB. 
The monotherapy treatment of 149 adults has provided a comprehensive database of safety 
information that allows the Sponsor to understand the potential AEs in the pediatric 
population. In addition, Takeda sponsored a second study (C28002; NCT 02327169) in 71 
patients with non–small cell lung carcinoma. While this study provides additional supportive 
data on DAY101, applicability of the safety data from this study to pediatric low-grade 
glioma patients is lower due to the fact that in study C28002, DAY101 was used in 

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V600 mutations), to provide treatment options to patients following the closure of Arm 1 and 
prior to commercial availability of DAY101. Arm 3 is to enroll patients with advanced solid 
tumors harboring activating RAF fusions (e.g., BRAF or CRAF/RAF1 fusions). 
1.3.1. 
Study Rationale 
Relapsed or progressive pediatric low-grade glioma is a serious, life-altering, and potentially 
fatal disease with significant disease- and treatment-associated morbidity. There is currently 
no standard of care for patients who progress after initial therapy and no FDA-approved 
therapies. As noted in Section 1.1, a significant body of data clearly shows that a majority of 
patients with pediatric low-grade glioma also have an alteration in BRAF that drives tumor 
growth: either a KIAA1549:BRAF fusion, or a BRAF V600 mutation. Type I BRAF 
inhibitors are mechanistically only able to inhibit the BRAF V600 mutations. Using a Type I 
RAF inhibitor in a patient with a BRAF fusion has the potential to cause paradoxical 
activation of the MAPK pathway and tumor growth. Because the majority of BRAF 
alterations in patients with pediatric low-grade glioma are BRAF fusions, use of Type I RAF 
inhibitors is not indicated. Currently approved MEK inhibitors can block MAPK signaling 
resulting from either BRAF V600 mutations or the KIAA1549:BRAF fusion, but do not 
directly inhibit BRAF. In addition, MEK inhibitors are associated with significant cardiac, 
dermatologic, and ophthalmologic toxicities. The Type II BRAF inhibitor DAY101 has been 
shown preclinically to be able to inhibit both BRAF V600 and BRAF fusion alterations, and 
has been shown to have significantly greater CNS penetration than any of the available 
Type I RAF inhibitors or MEK inhibitors.
As noted in Section 1.1.3.1, a significant number of patients with advanced solid tumors 
harboring a BRAF or CRAF/RAF1 fusion could benefit from potent and selective RAF 
kinase inhibition. The application of receptor tyrosine kinase inhibition to treat driver 
alterations across different tumor types and ages was demonstrated by the tissue-agnostic 
approval of larotrectinib in patients of any age with TRK fusion–positive solid tumors. An 
ORR of 75% by independent review was reported in 55 patients ranging from 4 months to 76 
years, spanning 17 different tumor histologies (Drilon et al. 2018). Similar tissue-agonistic 
activity of DAY101 is anticipated based on the mechanism of action targeting molecular 
subgroups. Recently, an 8-year-old male with a spindle cell sarcoma harboring a novel 
SNX8-BRAF fusion received DAY101 in a compassionate-use basis. The patient exhibited a 
near-complete response following two cycles of therapy (Offer et al. 2021). Treatment is 
ongoing at the time of this protocol finalization. 

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1.3.5. 
Continuous Review of Safety Data 
The eCRF used for this study allows real-time tracking of safety data. Safety data review will 
be reviewed by the Sponsor or designee regularly, and safety signals or trends will be 
escalated to the SRC and DSMB accordingly. 
Serious adverse events (SAEs) will be reported within 24 hours to the safety team by email 
and be subject to a second assessment by the safety physician (see Section 8.1.4). 
1.3.6. 
Potential Benefit for Patients in Clinical Trials and Patients in General 
The available nonclinical and clinical data of DAY101 predict responses in a clinically 
relevant group of patients.  
In patients with RAF-altered low-grade glioma, there have been two CRs, three PRs, 
two SDs, and two patients with primary progressive disease (ORR: 56%). Median TTR was 
10.5 weeks (range: 8–32 weeks) (see Section 1.2.2.2). Two patients reached end of treatment 
(i.e., completed two years of therapy). In addition, no patients with a confirmed response 
have progressed or discontinued therapy due to toxicity. One patient with a spindle cell 
sarcoma harboring a BRAF fusion, who was treated in a compassionate-use setting, has 
achieved a near-complete response (Offer et al. 2021). 
The expected high response rate and short TTR will potentially improve tumor burden and 
induced functional deficits such as visual and motor function impairment (see Section 1.1.2), 
associated with positive impact on growth and development of patients. 
Compared with the majority of currently applied chemotherapy regimens, which require 
hospitalization/in-patient treatment, patients enrolled in this study will receive an oral drug 
that is taken at home, allowing continuation of daily activities such as attending school. For 
future patients, the efficacy and safety data generated from this study can potentially address 
the unmet clinical need in treatment of patients with solid tumors harboring a BRAF 
alteration. 
1.3.7. 
Integrated Benefit/Risk Assessment 
As discussed in Sections 1.1.2 and 1.1.2.1, pediatric low-grade glioma is a highly morbid, but 
not a life-threatening, disease. Patients suffer from a relentless progression of symptoms 
directly related to a tumor growth in a closed space. Additionally, long-term survivors may 
experience considerable chronic toxicities as a result of the current standard approaches to 
therapy. The chances for cure in children with relapsed or refractory pediatric low-grade 
gliomas are minimal, which illustrates an unmet medical need for innovative treatment 
strategies in this population. Currently, there are no standard treatment options available for 
this patient group. The vast majority of patients receive non-controlled, individual 
experimental treatments outside of clinical trials according to institutional experience (see 
Section 1.1.2.1). 

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Advanced solid tumors harboring activating RAF fusions have an unmet medical need in 
identifying treatments specifically targeted to the oncogenic driver alteration, as discussed in 
Sections 1.1.3 and 1.3.1. Children and adolescents with relapsed or progressive solid tumors 
harboring an activating RAF fusion that have exhausted current therapeutic options do have a 
realistic potential to benefit from this study. 
Phase 1 clinical data of DAY101 in children confirmed the RP2D dose in the pediatric 
population (420 mg/m2, with a maximum dose of 600 mg) and confirm the same favorable 
safety profile as reported in adults. Nonclinical data detail CYP2C8 metabolism and low risk 
for drug-drug interaction. Clinical data from the Phase 1 trials confirm a safe and tolerable 
AE profile of DAY101 in adults. The study protocol adequately addresses safety concerns, 
such as potential male and female reproductive organ toxicity in pediatric patients, using 
measures of strict safety monitoring covering all foreseeable relevant toxicities and potential 
target organs, including adequate contraceptive measures. 
In summary, the nonclinical and clinical data in pediatric patients treated with DAY101 to 
date show a favorable benefit/risk profile for conducting this study in pediatric patients with 
RAF-altered CNS and other solid tumors that have not shown clinical improvement with 
current standard-of-care therapeutic regimens. 
2.
STUDY OBJECTIVES
Study objectives and endpoints are outlined in Table 4, Table 5, and Table 6. 
Table 4: 
Arm 1 (Low-Grade Glioma) Objectives and Endpoints 
PRIMARY OBJECTIVE AND ENDPOINTS 
OBJECTIVE 
ENDPOINTS 
x To evaluate the 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 low-grade
glioma harboring a known activating BRAF
alteration
x Overall response rate, defined as the proportion of
patients with best overall confirmed response of
complete response (CR) or partial response (PR) as
determined by the Response Assessment in
Neuro-Oncology (RANO) criteria
SECONDARY OBJECTIVES AND ENDPOINTS 
OBJECTIVE 
ENDPOINTS 
x To assess the safety and tolerability of DAY101
x Type, frequency, and severity of AEs and
laboratory abnormalities
x To determine the relationship between
pharmacokinetics (PK) and drug effects, including
efficacy and safety
x Pharmacokinetic profile of DAY101 (e.g., area
under the concentration-time curve [AUC@, Cmin,
etc.)

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x To characterize changes in total tumor volume
following treatment with DAY101 by magnetic
resonance imaging (MRI) volumetric image
analysis
x Measured by determining tumor volume and
volume changes based on MRI scan data
x To characterize changes in apparent diffusion
coefficients following treatment with DAY101
using diffusion-weighted imaging analysis
x Measured by diffusion-weighted imaging based on
MRI scan data
x To evaluate changes in quality-of-life and health
utilities measures using the Pediatrics Quality of
Life™—Core Module (PedsQL-Core), Pediatrics
Quality of Life™—Cancer (PedsQL-Cancer), and
Patient-Reported Outcomes Measurement
Information System (PROMIS®) assessment
x Measured by changes from baseline in
quality-of-life and health utilities measures using
the PedsQL-Core, PedsQL-Cancer, and PROMIS®
assessment
x To describe the improvement in motor function
x Measured by changes from baseline in the
Vineland 3 Adaptive Behavior Scales
x To determine the durability of response following
discontinuation of DAY101 for patients with a
radiographic response to DAY101 (CR or PR as
based on RANO and RAPNO criteria) as
determined by 1) an IRC and 2) the treating
investigator (RANO only)
x Measured by the proportion of patients with best
overall confirmed response of CR or PR who enter
a drug holiday period and time to progression as
determined by RANO, RAPNO, or clinical criteria
x To evaluate time to initiation of next treatment
following discontinuation of DAY101
x Measured by the proportion of patients who
discontinue DAY101 therapy and time to next
therapy initiation
Table 5: 
Arm 2 (Low-Grade Glioma Extension) Objectives and Endpoints 
PRIMARY OBJECTIVES AND ENDPOINTS 
OBJECTIVE 
ENDPOINTS 
x To assess the safety and tolerability of DAY101 in
pediatric patients aged 6 months to 25 years,
inclusive, with a relapsed or progressive low-grade
glioma harboring a known or expected to be
activating RAF alteration
x Type, frequency, and severity of AEs and
laboratory abnormalities
SECONDARY OBJECTIVES AND ENDPOINTS 
OBJECTIVE 
ENDPOINTS 
x To determine the ORR per RANO criteria as
determined by 1) an IRC and 2) the treating
investigator
x Measured by the proportion of patients with best
overall confirmed response of CR or PR as
determined by the RANO criteria
x To determine the ORR based on RAPNO–
low-grade glioma criteria as determined by an IRC
x Measured by the proportion of patients with best
overall confirmed response of CR or PR by
RAPNO–low-grade glioma criteria
x To evaluate the duration of PFS based on RANO
and RAPNO criteria following initiation of
DAY101 as determined by 1) an IRC and 2) the
treating investigator (RANO only)
x Measured by the time following initiation of
DAY101 to progression or death in patients treated
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x To evaluate the DOR in patients with BOR of CR
or PR based on RANO and RAPNO criteria as
determined by 1) an IRC and 2) the treating
investigator (RANO only)
x Measured by the length of response in patients
with best overall confirmed response of CR or PR
by RANO and RAPNO criteria, as applicable
x To evaluate TTR (CR or PR based on RANO and
RAPNO criteria) following initiation of DAY101
as determined by 1) an IRC and 2) the treating
investigator (RANO only)
x Measured by the time to first response following
initiation of DAY101 in patients with best overall
confirmed response of CR or PR by RANO and
RAPNO criteria, as applicable
x To evaluate the clinical benefit rate based on the
proportion of patients with BOR of CR, PR, or SD,
based on RANO and RAPNO criteria, lasting
12 months or more following initiation of
DAY101, as determined by 1) an IRC and 2) the
treating investigator (RANO only)
x Measured on the proportion of patients with BOR
of CR, PR, or SD lasting 12 months or more
following initiation of DAY101
x To determine the relationship between PK and
drug effects, including efficacy and safety
x Pharmacokinetic profile of DAY101 (e.g., AUC,
Cmin, etc.)
x To evaluate the effect of DAY101 on QTcF
prolongation and to explore the effects of DAY101
on ECG parameters
x ǻ47F)
x ǻ35
x ¨QRS
x ¨HR
x ECG waveform morphology
EXPLORATORY OBJECTIVES AND ENDPOINTS 
OBJECTIVES 
ENDPOINTS 
x To characterize changes in total tumor volume
following treatment with DAY101 by MRI
volumetric image analysis
x Measured by determining tumor volume and
volume changes based on MRI scan data
x To characterize changes in apparent diffusion
coefficients following treatment with DAY101
using diffusion-weighted imaging analysis
x Measured by diffusion-weighted imaging based on
MRI scan data
x To evaluate changes in BCVA outcomes
x Measured by change from baseline BCVA
(converted as logMAR) for each eye
x To evaluate changes in quality-of-life and health
utilities measures using the PedsQL-Core,
PedsQL-Cancer, and PROMIS® assessment
x Measured by changes from baseline in
quality-of-life and health utilities measures using
the PedsQL-Core, PedsQL-Cancer, and PROMIS®
assessment
x To describe the improvement in motor function
x Measured by changes from baseline in the
Vineland 3 Adaptive Behavior Scales
x To determine the durability of response following
discontinuation of DAY101 for patients with a
radiographic response to DAY101 (CR or PR as
based on RANO and RAPNO criteria) as
determined by 1) an IRC and 2) the treating
investigator (RANO only)
x Measured by the proportion of patients with best
overall confirmed response of CR or PR who enter
a drug holiday period and time to progression as
determined by RANO, RAPNO, or clinical criteria

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summary of changes. The Sponsor continues to plan for registration based on data from Arm 
1. The study design schema is shown in Figure 5.
Figure 5: 
Study Design Schema 
Abbreviations: pLGG, pediatric low-grade glioma.
The study will consist of a screening period, a treatment period, an end of treatment (EOT) 
visit, a safety follow-up visit, and long-term follow-up assessments. Ongoing safety, disease 
stability/progression, survival, and subsequent anticancer therapies will be assessed in the 
long-term follow-up period. 
For all arms, treatment cycles will repeat every 28 days in the absence of disease progression 
or unacceptable toxicity. Patients will continue on DAY101 until radiographic evidence of 
disease progression as determined by treating investigator, unacceptable toxicity, decision to 
enter a “drug holiday” period, patient withdrawal of consent, or death. 
Patients will be treated with DAY101 for a planned period of 26 cycles (approximately 
24 months), after which they may continue on DAY101 or, at any point, opt to enter a “drug 
holiday” discontinuation period. Patients will continue to undergo routine periodic 
radiographic evaluations per protocol-defined timelines during the discontinuation period and 
may be re-treated with DAY101 if there is radiographic evidence of disease progression after 
drug discontinuation. 
Patients who have radiographic evidence of disease progression may be allowed to continue 
DAY101 if, in the opinion of the investigator, and approved by the Sponsor, the patient is 
deriving clinical benefit from continuing study treatment. Patients being treated beyond 
progression with DAY101 will be reconsented prior to continuation of therapy. Disease 
assessments for patients being treated beyond progression should continue as per regular 
schedule. 
DAY101 will be administered at the RP2D dose of 420 mg/m2 (not to exceed 600 mg), PO 
QW (Days 1, 8, 15, and 22 of a 28-day cycle). Body surface area will be determined by the 

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Mösteller Formula >¥KHLJKWîZHLJKW@(Mosteller 1987). DAY101 is administered as 
an oral tablet or reconstituted liquid suspension formulation. 
A schedule of assessments is provided in Appendix A. The study treatment schema is shown 
in Figure 6. 
Figure 6: 
Treatment Schema 
Abbreviations: C, cycle; D, day; EOS, end of study; CT, computerized tomography; MRI, magnetic resonance 
imaging; SOA, schedule of assessments.
3.1.1.
Arm 1: Low-Grade Glioma 
Arm 1 will enroll patients aged 6 months to 25 years, inclusive, with recurrent or progressive 
low-grade glioma harboring a known activating BRAF alteration, including BRAF V600 
mutations and KIAA1549:BRAF fusions. Patients with BRAF alterations will be identified 
through molecular assays as routinely performed at Clinical Laboratory Improvement 
Amendments (CLIA) of 1988 or other similarly certified laboratories. 
Patients will undergo radiographic evaluation of their disease at the end of every third cycle, 
starting with the end of Cycle (C) 3 (i.e., on or up to seven days before C4 Day [D@1). 
Patients will continue on DAY101 until radiographic evidence of disease progression by 
RANO criteria as determined by treating investigator, unacceptable toxicity, decision to enter 
a “drug holiday” period after completion of 26 cycles, patient withdrawal of consent, or 
death. 
3.1.2.
Arm 2: Low-Grade Glioma Extension 
Arm 2 will enroll patients aged 6 months to 25 years, inclusive, with recurrent or progressive 
low-grade glioma harboring a known or expected to be activating RAF alteration (e.g., 
BRAF or CRAF/RAF1 fusion or BRAF V600 mutations). Patients with RAF alterations will 
be identified through molecular assays as routinely performed at CLIA-certified or other 
similarly certified laboratories.

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Once Arm 1 is approximately 90% enrolled (i.e., ~54 patients), the DSMB will convene to 
review all available safety and efficacy data (at a regularly scheduled meeting or on an ad 
hoc basis, as appropriate). After reviewing the data, the DSMB will make a formal 
recommendation based on assessment of benefit/risk as to whether to open Arm 2 to 
enrollment after Arm 1 is fully accrued. Arm 2 will remain open to enrollment during 
regulatory review of a marketing application for DAY101. Should Arm 1 not meet its 
primary endpoint, Arm 2 will immediately close to further enrollment. 
Patients enrolled in Arm 2 will undergo the same treatment and radiographic assessment 
schedule as Arm 1. Additional details can be found in the schedule of assessments 
(Appendix A). 
3.1.3. 
Arm 3: Advanced Solid Tumor 
Arm 3 will enroll patients aged 6 months to 25 years, inclusive, with advanced solid tumors 
harboring a known or expected to be activating RAF fusion (e.g., BRAF or CRAF/RAF1 
fusion). Patients with RAF fusions will be identified through molecular assays as routinely 
performed at CLIA-certified or other similarly certified laboratories. 
For this portion of this study, a modified Simon 2-stage design will be used to enroll up to 
approximately 20 patients based on evaluation of ORR (confirmed PR or CR per RECIST 
v1.1) (Simon 1989). The statistical assumptions will require approximately 12 evaluable 
patients in the first stage and 20 evaluable patients in total. In the first stage, if  1 objective 
response (PR or CR per RECIST v1.1) is seen in the first 12 patients, the study will stop any 
further recruitment and the treatment will be considered as not effective in this setting; 
however, if  2 responses occur, an additional eight patients will be recruited. 
Patients will undergo radiographic evaluation of their disease at the end of every second 
cycle, starting with the end of C2 (i.e., on or up to seven days before C3D1), and at the end 
of every two cycles through 12 months of treatment (i.e., on or up to seven days before 
C5D1, C7D1, etc.). Thereafter, patients will undergo radiographic evaluation at the end of 
every three cycles. Patients will continue DAY101 until radiographic evidence of disease 
progression by RECIST v1.1 criteria as determined by treating investigator, unacceptable 
toxicity, decision to enter a “drug holiday” period after completion of 26 cycles, patient 
withdrawal of consent, or death. 
3.1.4. 
End of Study and Length of Study 
The end of this study is defined as the date when the last visit occurs for the last patient 
enrolled. The end of the study is expected to occur 25 months after the last patient is enrolled 
into Arm 1. 
In addition, the Sponsor may decide to terminate the study at any time. 
The total length of the study, from screening of the first patient to the end of the study, is 
expected to be approximately four years. 

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3.1.5. 
Number of Patients 
Approximately 140 patients in total will be enrolled across all treatment arms of this study. 
The arms will be enrolled as follows: 
x
Arm 1: Approximately 60 patients
x
Arm 2: Up to 60 patients
x
Arm 3: Up to 20 patients
Patients will be considered as enrolled when they have ingested a dose of DAY101 on C1D1. 
3.2. 
Investigational Sites 
Approximately 40 institutions will participate in this study. 
4.
SELECTION OF STUDY POPULATION
Potential patients and/or their parents must sign an informed consent form (ICF) and 
pediatric assent form, where applicable, before any study-specific screening tests may be 
conducted. 
4.1. 
Inclusion Criteria 
Patients must meet all of the following criteria to be eligible for enrollment in the study: 
1. Patients must be age 6 months to 25 years, inclusive, with:
a) Arm 1 (Low-Grade Glioma): A relapsed or progressive low-grade glioma with a
documented known activating BRAF alteration, as identified through molecular
assays as routinely performed at CLIA or other similarly certified laboratories
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, as identified through molecular assays as routinely performed at
CLIA-certified or other similarly certified laboratories
c) Arm 3 (Advanced Solid Tumor): Locally advanced or metastatic solid tumor with
a documented known or expected to be activating RAF fusion, as identified
through molecular assays as routinely performed at CLIA-certified or other
similarly certified laboratories, that has relapsed or progressed or was
nonresponsive to available therapies and for which no standard or available
systemic curative therapy exists
2. Patients must have histopathologic verification of malignancy at either original diagnosis
or relapse.
3. Patients must have received at least one line of prior systemic therapy and have
documented evidence of radiographic progression.
4. Patients must have evaluable and/or measurable disease (imaging must be performed
within 28 days of the initiation of treatment) as specified below:
a) Arm 1 (Low-Grade Glioma): Must have at least one measurable lesion as defined
by RANO criteria (T1-weighted lesion that can be reproducibly measured in at

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least 2 dimensions of at least 10 mm, visible on 2 or more axial slices that are 
preferably, at most, 5 mm apart with 0-mm skip) 
b) Arm 2 (Low-Grade Glioma Extension): Must have evaluable (either
unidimensionally measurable lesions, masses with margins not clearly defined, or
lesions with maximal perpendicular diameters less than 10 mm) and/or
measurable disease as defined by RANO criteria
c) Arm 3 (Advanced Solid Tumor): Must have at least one measurable lesion as
defined by RECIST v1.1 ( 10 mm by CT/MRI VFDQ>VOLFHWKLFNQHVV 5 PP@
 20 mm by chest X-UD\RU 10 mm with calipers by clinical exam, or pathologic
O\PSKQRGHVZLWKDVKRUWD[LVRI 15 mm by CT scan/MRI)
5. Radiation therapy to the measurable lesion(s) must be completed at least six months prior
to administration of DAY101. Patients who have documented radiographic progression
less than six months from radiotherapy in one or more measurable lesions are eligible.
6. Patients must have Karnofsky (those 16 years and older) or Lansky (those younger than
16 years) performance score of at least 50. Patients who are unable to walk because of
paralysis, but who are able to sit in a wheelchair, will be considered ambulatory for the
purpose of assessing the performance score.
7. Patients must have fully recovered from the acute toxic effects of all prior anticancer
chemotherapy and have undergone the following washout periods, as applicable:
a) Myelosuppressive chemotherapy: At least 21 days must have elapsed after the last
dose of myelosuppressive chemotherapy (42 days if prior nitrosourea).
b) Radiation therapy (XRT): At least 14 days must have elapsed after the last dose
fraction of XRT.
c) Stem cell transplant or adoptive cell therapy: At least 100 days must have elapsed
after cell infusion.
d) Investigational agent or any other anticancer therapy not defined above: At least
four weeks prior to planned start of DAY101, or five half-lives, whichever is
shorter.
8. Chronic toxicities from prior anticancer therapy must be stable and at Common
Terminology Criteria for Adverse Events (CTCAE) version *UDGH.
a) Ongoing retinopathy PXVWEH*UDGH.
9. Patients must have fully recovered from any prior surgery.
10. An archival tumor tissue sample must be available. If an archival tumor tissue sample is
not available, a fresh biopsy should be performed at baseline. For patients enrolling to
Arm 2 (Low-Grade Glioma Extension) that do not have archival tumor tissue, enrollment
may be considered on a case-by-case basis following a discussion between the
investigator and the Day One Medical Monitor.
11. Patients must have adequate hematologic function, as defined by the following:
a) $EVROXWHQHXWURSKLOFRXQWPP3
b) 3ODWHOHWFRXQWu 109/L (transfusions allowed per institutional guidelines;
last transfusion > 2 weeks prior to C1D1)
c) +HPRJORELQ 10.0 g/dL (transfusions allowed per institutional guidelines; last
transfusion > 4 weeks prior to C1D1)

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d) Hematopoietic growth factors: At least 14 days after the last dose of a long-acting
growth factor (e.g., Neulasta®) or seven days for short-acting growth factor
12. Patients must have adequate hepatic and renal function, defined by the following:
a) 7RWDOELOLUXELQ 1.5 u upper limit of normal (ULN) for age (patients with
documented Gilbert’s Disease may be enrolled with Sponsor approval and total
ELOLUXELQ 2.0 u ULN)
b) Serum glutamic-pyruvic transaminase (SGPT)/alanine aminotransferase (ALT)
 2.5 u ULN
c) Serum glutamic-oxaloacetic transaminase (SGOT)/aspartate transaminase (AST)
 2.5 u ULN
d) Serum creatinine within normal limits, or estimated glomerular filtration rate
 60 mL/min/1.73 m2 based on local institutional practice for determination
13. Thyroid function tests must be consistent with stable thyroid function. Patients on a stable
dose of thyroid replacement therapy for a minimum of three weeks before starting
DAY101 are eligible.
14. Patients must have lHIWYHQWULFXODUHMHFWLRQIUDFWLRQ/9()RIDVPHDVXUHGE\
echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan, or fractional
VKRUWHQLQJ)6 25% (Tissot et al., 2018) as measured by ECHO, within 28 days before
the first dose of DAY101. If normal practice at the institution is to provide the LVEF
result as a range of values, then the upper value of the range will be used to determine the
result.
15. Patients receiving steroids for tumor-associated symptoms must be on a stable dose (e.g.,
no initial/loading dose, no increase or decrease) for 14 days prior to C1D1.
16. Patients must be able to comply with treatment, laboratory monitoring, and required
clinic visits for the duration of study participation.
17. Male and female patients with reproductive potential must be willing to use a highly
effective birth control method for the duration of treatment and for 180 days following
the last dose of study drug. Highly effective birth control methods are described in
Appendix K.
18. Patients must have ability to swallow tablets or liquid or be willing to comply with
administration of a nasal or gastric tube for gastric access.
19. Parent/guardian of child or adolescent patient must have the ability to understand, agree
to, and sign the study ICF and applicable pediatric assent form before initiation of any
protocol-related procedures; patient must have the ability to give assent, as applicable, at
the time of parental/guardian consent.
4.2. 
Exclusion Criteria 
Patients meeting any of the following criteria are to be excluded from study participation: 
1. Patient’s tumor has an additional previously known or expected to be activating
molecular alteration(s) (e.g., histone mutation, IDH1/2 mutations, FGFR mutations or
fusions, MYBL alterations, NF-1 somatic or germline mutations).
2. Patient has symptoms of clinical progression without radiographically recurrent or
radiographically progressive disease.

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3. Patient has known or suspected diagnosis of neurofibromatosis type 1 (NF-1) via genetic
testing or current diagnostic criteria.
4. Patient has history of any major disease, other than the primary malignancy under study,
that might interfere with safe protocol participation.
5. Patient has a history or current evidence of central serous retinopathy (CSR), retinal vein
occlusion (RVO), or ophthalmopathy present at baseline that would be considered a risk
factor for CSR or RVO. Ophthalmological findings secondary to long-standing optic
pathway glioma (such as visual loss, optic nerve pallor, or strabismus) will NOT be
considered significant abnormalities for the purposes of this study.
6. Patient has major surgery within 14 days (two weeks) prior to C1D1 (does not include
central venous access, cyst fenestration or cyst drainage, or ventriculoperitoneal shunt
placement or revision).
7. Patient has clinically significant active cardiovascular disease, or history of myocardial
infarction, or deep vein thrombosis/pulmonary embolism within six months prior to
C1D1, ongoing cardiomyopathy, or current prolonged QT interval corrected for heart rate
by Fridericia’s formula (QTcF) interval > 470 milliseconds based on triplicate
electrocardiogram (ECG) average.
8. Patient is currently enrolled in any other investigational treatment study. Participation in
a concurrent observational or bio-sampling study is allowed.
9. Patient has active systemic bacterial, viral, or fungal infection.
10. Patient has nDXVHDDQGYRPLWLQJNational Cancer Institute (NCI) Common
Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade 2, malabsorption
requiring supplementation, or significant bowel or stomach resection that would preclude
adequate absorption of DAY101.
11. Patient is neurologically unstable despite adequate treatment (e.g., uncontrolled seizures).
12. Patient is currently being treated with a strong CYP2C8 inhibitor or inducer other than
those allowed per Section 5.3.2. Medications that are substrates of CYP2C8 are allowed
but should be used with caution.
13. Patient is pregnant or lactating.
14. Patient has a history of any drug reaction with eosinophilia and systemic symptoms
(DRESS) syndrome or Stevens Johnsons syndrome (SJS), or hypersensitivity to the
investigational medicinal product or to any drug with similar chemical structure or to any
other excipient present in the pharmaceutical form of the investigational medicinal
product.
15. There are other unspecified reasons that, in the opinion of the investigator, make the
patient unsuitable for enrollment.
5.
TREATMENT
5.1. 
Investigational Product 
DAY101 for oral dosing is provided as an immediate-release tablet in one strength, 100 mg. 
The 100-mg tablets are red to yellowish red oval tablets and labeled DAY101. In addition, 
DAY101 is provided in bottles as a powder for reconstitution (430 mg per bottle to deliver 

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300-mg dose) that is reconstituted with water to form a suspension with a concentration of
25 mg/mL.
The site pharmacist will dispense the tablets. The powder for reconstitution will be dispensed 
to the patient in a kit containing a dosing syringe and bottle adaptor, or to the patient’s parent 
or legal guardian, in an amount necessary to allow for outpatient administration. Further 
information is provided in the Pharmacy Manual. 
DAY101 tablets are to be stored at controlled room temperature (between 15°C and 25°C) 
and protected from light. DAY101 powder for reconstitution is to be stored at controlled 
room temperature (between 15°C and 25°C) and protected from light. Additional details 
regarding the investigational product are provided in the DAY101 IB. 
5.2. 
DAY101 Administration 
5.2.1. 
General Dosing Instructions 
Dosing for an individual should be at a consistent day and time (± 12 hours) each week. 
There is no restriction with regard to intake of food (patients can be fed or fasted). Tablets 
should not be cut or crushed. The powder for reconstitution will be reconstituted with water 
using the provided dosing syringe, and the resulting liquid suspension will be administered 
orally or enterally via a nasal or gastric feeding tube with a dosing syringe. 
If the patient spits up a portion of the oral suspension, the patient or parent or legal guardian 
should be instructed to call the study doctor or nurse to discuss if they should take any 
additional suspension. If after two attempts the patient does not swallow the dose, it will be 
considered a “missed” dose. Record the missed dose in the diary as “missed” and note next to 
the entry that the patient “spit up the dose.” If the patient swallows the oral suspension and 
vomits after ingesting it, another dose should not be given at that time. 
If the patient vomits the tablets and they are still recognizable, then the patient can be 
redosed. If the patient vomits within 30 minutes of ingesting tablets and the tablets are not 
recognizable, the patient or parent or legal guardian should be instructed to call the 
investigator or study nurse to discuss whether the patient should take any additional tablets. 
If it has been longer than 30 minutes or the investigator or study nurse is not reachable, the 
patient should not be redosed. 
The patient, or the patient’s parent or legal guardian, will complete a study drug 
administration diary to record dosing compliance. The study drug administration diary will 
be reviewed at each clinic visit by the investigator or study nurse.  
Late doses (i.e., between 12 and 72 hours of regularly scheduled dose) should be noted in the 
diary. Doses that are late by more than 72 hours (three days) should be skipped and recorded 
in the dosing diary as missed. A minimum of four days should occur between doses. Any 
dose that cannot be given within three days of the scheduled dose should be recorded as 

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missed. Dose rounding guidelines for tablets are provided in Table 7. Dose rounding 
guidelines for the reconstituted liquid suspension are provided in Table 8. 
All patients will be initiated on DAY101 at 420 mg/m2 according to the patient’s baseline 
BSA. Patients with a BSA of 0.6m2 or less will be required to receive the liquid suspension 
formulation. If appropriate in the opinion of the investigator, patients may change 
formulations at any point during treatment (see Section 6.8 for PK sampling instructions). 
Table 7: 
Dose Rounding Guidelines for DAY101 Tablets (100 mg) 
BSA 
(m2) 
Second Dose Reduction 
(mg) 
First Dose Reduction 
(mg) 
Starting Dose 
420 mg/m2 
(mg) 
0.3 
Liquid formulation required; please see Table 8. 
0.4 
0.5 
0.6 
0.7 
100 
200 
300 
0.8 
100 
200 
300 
0.9 
200 
300 
400 
1.0 
200 
300 
400 
1.1 
300 
400 
500 
1.2 
300 
400 
500 
1.3 
400 
500 
600 
1.4 
400 
500 
600 
1.5 
400 
500 
600 
1.6 
400 
500 
600 
1.7 
400 
500 
600 
1.8 
400 
500 
600 
 1.9 
400 
500 
600 
Abbreviations: BSA, body surface area. 

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Table 8: 
Dose and Volume Rounding Guidelines for DAY101 Reconstituted 
Liquid Suspension (25 mg/mL) 
BSA 
(m2) 
Second Dose Reduction 
First Dose Reduction 
Starting Dose 
420 mg/m2 
Suspension Volume 
(mL) 
Suspension Volume 
(mL) 
Suspension Volume 
(mL) 
0.3 
3 
4 
5 
0.4 
4 
5 
7 
0.5 
5 
7 
8 
0.6 
6 
8 
10 
0.7 
8 
10 
12 
0.8 
9 
11 
13 
0.9 
10 
12 
15 
1.0 
11 
14 
17 
1.1 
12 
15 
18 
1.2 
13 
17 
20 
1.3 
15 
18 
22 
1.4 
16 
20 
24 
1.5 
16 
20 
24 
1.6 
16 
20 
24 
1.7 
16 
20 
24 
1.8 
16 
20 
24 
 1.9 
16 
20 
24 
Abbreviations: BSA, body surface area. 
Any questions regarding dose rounding should be directed to the Medical Monitor. 
Body surface area should be calculated on D1 of each cycle to confirm dose. The dose should 
be increased or decreased for any change in BSA greater than 10% on D1 of any cycle. The 
maximum dose will be no higher than the adult RP2D of 600 mg QW, established in the 
adult Phase 2 trial (C28001), regardless of the patient’s BSA. 
Refer to the pharmacy manual for additional dosing details. 
5.2.2. 
Dose Modifications 
National Cancer Institute (NCI) CTCAE version 5.0 should be used when evaluating 
unacceptable toxicities. According to the CTCAE, adverse reactions are reported by grade 
(level of severity) on a scale of Grades 1 to 5. Generally, the descriptions for adverse 
reactions by grade level (scale of Grades 1 to 5) follow the guidelines outlined below in 
Table 15. 

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The dose of DAY101 may be reduced at the discretion of the investigator for an AE that is 
clinically or medically intolerable. Patients who experience an AE that is clinically or 
medically intolerable, or otherwise described in Section 5.2.3, should have DAY101 dosing 
interrupted until resolution to Grade 1 or baseline level. Patients should be reevaluated at 
least weekly for resolution of the AE. Upon resolution, dosing may be restarted at the same 
dose or reduced to a lower dose of DAY101 at the discretion of the investigator (refer to 
Table 7 and Table 8). If the dose is reduced, re-escalation to a higher dose may be permitted 
after approval by the Sponsor. 
All patients who experience drug-related toxicity requiring a recovery period longer than 
28 days will be withdrawn from study drug administration unless there is evidence of benefit 
and no alternative treatment available as determined by the investigator and approved by the 
Sponsor. 
5.2.3. 
Management of Treatment-Related Events 
Included below are toxicity management guidelines. Modification of DAY101 dose is 
outlined in Section 5.2.2. 
Table 9: 
Treatment-Emergent Adverse Events Requiring Dose Interruption Until 
5HVROXWLRQWR Grade 1 or Baseline 
Drug-Related Toxicity 
Dose Hold Criteria 
Hematologic 
CTCAE Grade 4 anemia 
CTCAE Grade 4 thrombocytopenia or 
CTCAE Grade 3 thrombocytopenia with Grade 1 or higher 
bleeding 
CTCAE Grade 4 neutropenia 
Vomiting 
CTCAE Grade 3 or 4 only if it persists for > 72 hours despite 
standard-of-care treatment 
Note: Admission to the hospital for patients < 1 year of age with 
Grade 3 or 4 vomiting will be required until these events resolve 
to Grade 1. 
Diarrhea 
CTCAE Grade 3 or 4 only if it persists for > 72 hours despite 
standard-of-care treatment 
Note: Admission to the hospital for patients < 1 year of age with 
Grade 3 or 4 diarrhea will be required until these events resolve to 
Grade 1. 
Rash, HFSR, or photosensitivity 
CTCAE Grade 3 lasting > 8 consecutive days despite skin toxicity 
treatment, as per local practice, or 
CTCAE Grade 4 

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Drug-Related Toxicity 
Dose Hold Criteria 
Retinal disorder  
(e.g., retinal detachment/tear, retinal 
vascular disorder, retinopathy) 
&7&$(*UDGHFRQILUPHGE\RSKWKDOPRORJLFH[DPLQDWLRQ 
Visual disturbances without ocular 
(retinal) changes 
&7&$(*UDGH 
Other events 
&7&$(*UDGHH[FHSWIRUWKHexceptions noted below 
Exceptions to dose hold criteria 
CTCAE Grade 3 fatigue only if it persists for < 5 days 
CTCAE Grade 3 edema only if it persists for < 5 days 
Asymptomatic CTCAE Grade 3 laboratory abnormalities 
Abbreviations: CTCAE, Common Terminology Criteria for Adverse Events; HFSR, hand-foot skin reaction. 
The toxicities in Sections 5.2.3.1 through 5.2.3.5 have been observed with DAY101 
administration or have been observed with other therapies that have a similar mechanism of 
action. 
5.2.3.1. 
Ocular Disturbances 
An eye examination will be performed by an ophthalmologist if visual abnormalities are 
described by the patient. Careful monitoring of eye complaints should be followed, and the 
eye examination should include the clinically indicated assessments (e.g., slit-lamp 
examination of the cornea, retinal photographs, and intraocular pressure measurements). 
Patients must be instructed to report visual symptoms as soon as they occur. Early and 
aggressive dose interruption of mild visual symptoms may avoid more serious ocular 
complications. 
5.2.3.2. 
Photosensitivity 
Photosensitivity is a recognized class effect of RAF kinase inhibitors. Patients should avoid 
excess exposure to sunlight and UV light and use broad-spectrum sunscreen (e.g., containing 
titanium dioxide or zinc oxide) with a skin protection factor (SPF)  30. Patients should be 
instructed to monitor for signs and symptoms of photosensitivity (e.g., itchy eruptions or 
areas of redness and inflammation on patches of sun-exposed skin). 
5.2.3.3. 
Rashes 
Rashes (maculopapular, dermatitis acneiform, and pruritis) have been observed with 
DAY101 administration. Patients should be referred to a dermatology department when 
symptoms are impairing function (e.g., cannot sleep, sit still) or psychosocially bothersome, 
and when management techniques fail to resolve. 
Should a rash occur, see Appendix H for management options. 
5.2.3.4. 
Increased Creatine Phosphokinase 
While an asymptomatic increase in CPK level alone is not reason to reduce the dose of 
DAY101, it is important to rule out an accompanying clinical condition. See the 
recommendations in Table 10. 

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Table 10: 
Increased Creatine Phosphokinase Recommendations 
AE Grade 
Event Definition 
Recommendation 
Grade 1 
> ULN – 2.5 × ULN
x
Rule out increased physical activity, trauma, falls, muscle
injury
x
Rule out concomitant use of statins or excessive
environmental and other causes (e.g., alcohol, drugs, toxins,
heat illness, seizures, etc.)
x
Adequate hydration is recommended to maintain fluid and
electrolyte balance and tissue perfusion
Grade 2 
> 2.5 × ULN –
5 × ULN
x
Rule out increased physical activity, trauma, falls, muscle
injury
x
Rule out concomitant use of statins or excessive
environmental or other causes (e.g., alcohol, drugs, toxins,
heat illness, seizures, etc.)
x
BUN, creatinine, urinalysis
x
Myoglobin test in urine (urine dipstick, heme +, RBC í)
Grade 3/ 
Grade 4 
> 5 × ULN –
10 × ULN
> 10 × ULN
x
Rule out increased physical activity, trauma, falls, muscle
injury
x
Rule out concomitant use of statins or excessive
environmental or other causes (e.g., alcohol, drugs, toxins,
heat illness, seizures, etc.)
x
BUN, creatinine, urinalysis
x
Myoglobin test in urine (urine dipstick, heme +, RBC í)
x
In the presence of chest pain, test levels of troponin I or
troponin T
Abbreviations: AE, adverse event; BUN, blood urea nitrogen; RBC, red blood cell; ULN, upper limit of 
normal. 
Source: Common Terminology Criteria for Adverse Events, version 5.0. 
5.2.3.5. 
Increased Liver Transaminases 
Per the DAY101 IB, Grade 3 or higher elevations in aspartate aminotransferase (AST) have 
been observed in up to 5% of patients enrolled in Study C28001 with baseline AST/ALT 
elevations < 2.5 × ULN at study entry. This treatment plan allows a baseline AST/ALT 
elevation of up to 2.5 × ULN at enrollment. Should an increase in AST/ALT be observed 
while receiving DAY101, the recommendations from Table 11 should be followed. 

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Table 11: 
Increased Liver Transaminases Recommendations 
Event Definition 
Recommendation 
Asymptomatic, absolute increase in AST or ALT 
to > 5 × 8/1EXW × increase from baseline 
x
Do not modify the dose of DAY101
$V\PSWRPDWLF*UDGH$67RU$/7
AND > 2 × increase from baseline 
x
Withhold DAY101 until the laboratory
abnormality resolves to < 5 × ULN or baseline
x
The patient may resume taking the original
dose of DAY101 if the AST or ALT
abnormality resolves within 8 days.
x
Patients whose resolution of AST or ALT
abnormality is taking longer than 8 days may
have their DAY101 dose decreased by 1 dose
level to the next lower dose (once weekly).
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of 
normal. 
5.3. 
Prior and Concomitant Medications 
5.3.1. 
General 
All medications that were used from 28 days prior to enrollment through the end of study 
participation will be recorded in the electronic case report form (eCRF). All prior anticancer 
treatments, regardless of when they were administered, will also be collected. These are to 
include prescription medications and transfusions. Excluded prior medications are those 
excluded via the eligibility criteria (Section 4.2). 
5.3.2. 
Allowed Concomitant Medications 
The investigator should instruct the patient or the patient’s parent or legal guardian to notify 
the study site about any new medications he/she takes after starting study drug. 
Patients taking medication chronically should be maintained on the same dose and schedule 
throughout the study period, as medically feasible. The days of full PK blood sampling 
should be representative of the other study days with regard to the use of the chronically 
administered concomitant medications. However, if a concomitant medication is used 
intermittently during the study, this medication should be avoided on the days of full PK 
sampling, if medically feasible. 
In general, the use of any concomitant medication/therapies deemed necessary for the care of 
the patient is permitted, except as specifically prohibited in Section 5.3.3. Please refer to the 
DAY101 IB for possible interactions with other drugs. Medications required to treat AEs and 
manage cancer symptoms and concurrent stable diseases, and supportive care agents, such as 
pain medications, antiemetics, short courses of steroids, and antidiarrheals, are allowed. Oral 
contraceptive pills are permitted. 

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As a general precaution, patients receiving concomitant medications, particularly those with 
narrow therapeutic indices, should be carefully monitored, as potential drug-drug interactions 
between DAY101 and other drugs have not been studied in humans. Patients should also be 
instructed to consult with the investigator before taking any new medications, including 
over-the-counter products. 
Routine vaccinations, including the COVID-19 vaccine, should be administered per local 
institutional guidelines. 
5.3.3. 
Prohibited Concomitant Medications 
As DAY101 is a substrate of CYP2C8, patients should not take strong inhibitors or inducers 
of CYP2C8 (refer to Appendix C), as they could alter the drug’s PK. Medications that are 
substrates of CYP2C8 are allowed, but should be used with caution. Medications that are 
substrates of breast cancer resistance protein (BCRP) are prohibited during this study. During 
this study, patients are not allowed to receive other chemotherapeutic agents (traditional 
chemotherapy, targeted agents, monoclonal antibodies, etc.), drugs with immunosuppressant 
properties (other than steroids as allowed per Section 5.3.2), herbal supplements, or any other 
investigational agents besides DAY101. 
5.3.4. 
Concurrent Surgery 
Patients may undergo surgical intervention and remain on study when, in the opinion of the 
treating investigator, surgery is indicated for anything other than tumor resection for clinical 
or radiographic disease progression (e.g., cyst decompression, cerebrospinal fluid shunt 
revision). Therapy should be held for six days before intervention. Patients undergoing 
surgical intervention are permitted to restart study treatment six days following surgical 
intervention after discussion with and approval by the Sponsor. The surgical intervention 
should be recorded on the appropriate eCRF. For patients requiring surgical intervention due 
to clinical or radiographic evidence of tumor progression, patients should be withdrawn from 
study. 
If surgery is clinically indicated while on study, the Sponsor will request a tumor specimen 
and a concurrent PK sample. A separate tissue collection ICF will be provided. Please see 
details regarding surgical sample collection in Section 6.5. 
Arm 3 (Advanced Solid Tumor) only: For patients who receive DAY101 therapy prior to 
attempted surgical resection, DAY101 should be continued until a tumor is deemed to be 
resectable by the investigator. While timing of surgery is not protocol specified, ideally 
surgery should occur within three months of best radiographic response. If the resection 
surgery results in negative margins and study treatment is stopped, disease assessments, as 
described in Appendix A, should be performed every three months following the last dose of 
study medication. Patients whose treatment is stopped for this reason are permitted to restart 
study treatment if they experience disease recurrence only after discussion with the Medical 
Monitor. Patients who restart therapy will undergo assessments as if they were on study as 
outlined in Appendix A. 

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Patients who receive DAY101 and go on to an attempt at surgical resection will be re-staged 
at the time of surgery. Staging will be defined according to the tumor, node, metastasis 
(TNM) classification system: T1 (localized to the organ or tissue of origin) or T2 (extending 
beyond the tissue or organ of origin) according to the invasion of contiguous organs; N0 or 
N1 and M0 or M1 according to the presence of lymph node or distant metastasis. Lymph 
node involvement should be evaluated clinically or by radiographic imaging and confirmed, 
when necessary, by cytological or histological biopsy. 
The status of resection margins will be classified according to the UICC-R classification and 
the Intergroup Rhadbomyosarcoma Staging (IRS) systems, which is generally used for 
primary surgery in pediatric rhabdomyosarcomas. UICC-R R0 or IRS Group I will 
correspond to complete tumor resection with histologically free margins; UICC-R R1 or IRS 
II will correspond to macroscopic resection but invaded margins on histology; UICC-R R2 or 
IRS III correspond to macroscopic residual tumor after surgery (III B) or biopsy (III A). IRS 
IV corresponds to distant metastatic tumor. 
Patients who undergo surgical resection for local control may continue to receive DAY101 
after surgical recovery and discussion between the investigator and the Sponsor. 
5.3.5. 
Palliative Radiotherapy 
In general, measurable lesions being used to measure response should not be irradiated 
without discussion with the Sponsor, and may be reason for the patient to be removed from 
study for progressive disease. Irradiated non-measurable lesions will be considered not 
evaluable for response, but still can be used to assess progressive disease. The intensities, 
number, and dates of doses received for allowed palliative radiotherapy should be recorded 
on the appropriate eCRF. 
Palliative radiotherapy to specific sites of disease is permitted if considered medically 
necessary by the treating physician. DAY101 should be held for six days before intervention. 
These patients are permitted to restart study treatment six days following radiotherapy after 
discussion with and approval by the Sponsor. 
5.4. 
Removal of Patients from Therapy or Assessment 
Patients will be advised that they are free to withdraw from the study at any time. Patients 
who withdraw from therapy but do not withdraw consent will be followed for long-term 
follow-up. Over the course of the study, the investigator and/or the Sponsor may withdraw a 
patient from treatment for any of the reasons listed below: 
x
Disease progression as assessed by the investigator using RANO (Arms 1 and 2:
Low-Grade Glioma) or RECIST v1.1 (Arm 3: Advanced Solid Tumor) criteria, as
applicable. Patients may continue treatment beyond progression if, in the opinion
of the investigator and with permission of the Sponsor, the patient is deriving
clinical benefit from continued study treatment.
x
Unacceptable toxicity that does not improve after dose reduction(s)

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x
Intercurrent illness compromising the ability to fulfill protocol requirements
x
Dosing interruption > 28 days, unless resumption of treatment approved by the
Sponsor
x
Requirement for alternative treatment in the opinion of the investigator
x
Significant noncompliance to protocol
x
Pregnancy
x
Withdrawal of consent or assent by the patient or the patient’s parent or legal
guardian
x
Loss to follow-up
x
Death
When a patient withdraws from treatment, the patient should undergo the EOT visit, as 
outlined in Section 6.14. 
6.
TESTS AND EVALUATIONS
All required observations and schedules are described in more detail in Sections 6.1 through 
6.17, and summarized in Appendix A. 
Most study assessments and procedures (including treatment administration) will be 
performed in cycles, defined as 28-day intervals starting with the date of DAY101 
administration at baseline. Unless otherwise indicated, in the absence of toxicity, all 
scheduled visits will occur within windows for the protocol-specified visit schedule. If the 
patient is unable to have a study assessment within the defined time window due to an event 
outside of his or her control (e.g., clinic closure or travel restrictions due to COVID-19, 
personal/family emergency, inclement weather), the assessment should be performed as close 
as possible to the required schedule. 
6.1. 
Screening 
The screening procedures must be conducted within 28 days prior to C1D1, unless otherwise 
noted. Patients who cannot complete the procedures within the screening window may be 
rescreened as many times as the investigator deems appropriate. Procedures that were 
obtained as part of the patient’s standard care prior to providing informed consent for this 
study do not need to be repeated, with the exception of tumor imaging, which must be 
repeated if the prior imaging does not collect the appropriate sequences required for study as 
defined in the Imaging Manual. All patients receiving protocol therapy will have historical 
scans from the 12-month period immediately prior to the eligibility scan (if available) 
transferred to the central imaging laboratory as specified in the Imaging Manual. 
Screening tests that are completed in the 48 hours prior to start of DAY101 and duplicate 
C1D1 tests according to the schedule of assessments (Appendix A) will be accepted as 

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fulfilling the C1D1 assessments. Repeat testing on C1D1 is not necessary for this scenario, 
and results should be recorded in the screening set of eCRFs. 
A representative from the investigational site will enter demographic data for potential study 
candidates into the interactive response technology (IRT) system. The IRT system will assign 
potential study candidates a unique patient identification number. The patient identification 
number will be entered onto an eligibility form. A completed eligibility form will be sent to 
the Sponsor or designee when a potential study candidate is identified. Any reports (e.g., 
pathology report, radiology report) supportive to the eligibility form must have Protected 
Health Information (name, date of birth, address, parents’ names, medical record number, 
etc.) removed prior to submission to Sponsor. The site representative will be contacted by 
either the Sponsor or its designee to 1) confirm eligibility, or 2) provide additional 
information. 
Patients who are determined to be screen failures can be rescreened. Rescreened patients will 
maintain the same unique patient number assigned to them originally by the IRT system. Site 
representatives should not enter revised screening data into the IRT, as a new patient 
identification number need not be assigned. A revised eligibility form should be submitted to 
the Sponsor or its designee for rescreened patients. See the Study binder for eligibility form, 
patient number assignment, contact numbers, and other details of enrollment. 
The approved eligibility form will be returned to the site with the cohort assignment (if 
applicable) as verification of eligibility in the trial, and for record-keeping purposes. 
6.2. 
Enrollment 
Enrollment procedures will be conducted in accordance with the schedule of assessments 
(Appendix A). Patients who meet the eligibility criteria outlined in Section 4.1 will be 
enrolled in this study. 
6.3. 
Procedure Details 
Timing of assessments and further details of assessments can be found in the Appendices. 
6.4. 
Medical History and Malignancy History 
Medical, surgical, and malignancy history, including histologic confirmation of tumor, 
primary tumor diagnosis and recurrence dates, prior treatments, treatment dates, tumor 
responses, etc., should be recorded on the appropriate eCRF. Demographics, including age, 
sex, race, and ethnicity, will be recorded. 
Arm 3 (Advanced Solid Tumor) only: In addition to the histories described above, patients 
who receive DAY101 and go on to surgery will be staged by conventional TNM 
classification at study entry and again at the time of en bloc surgical resection. As part of 
screening procedures, the investigator will collect in the electronic data capture (EDC) 
system the patient’s treatment plan, including surgical procedure and anticipated outcomes 

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(amputation, functional deficit, etc.) had they not enrolled in this study. The surgical path 
specimen will be collected and submitted for central pathology review. 
6.5. 
Archival Tumor 
Archival tumor samples representing current disease status are required for all patients during 
screening. (Patients enrolling to Arm 2 [Low-Grade Glioma Extension@ who do not have 
archival tissue may be considered for enrollment on a case-by-case basis after discussion 
between the investigator and the Day One Medical Monitor.) Archival tumor tissue may 
come from a specimen obtained at either diagnosis or recurrence. Tumor samples may be 
either formalin-fixed, paraffin-embedded (FFPE) tissue or fresh frozen tissue. If an archival 
tumor tissue sample is not available, a fresh biopsy should be performed at baseline. Tissue 
collection on-study or at the EOT visit is optional. 
An optional tumor tissue sample from patients who undergo on-study, tumor-directed surgery 
is requested. 
6.6. 
Safety Assessments 
6.6.1. 
Physical Examination 
Physical examinations will also include review of systems (chest, extremities, genitourinary, 
head/ears/eyes/nose/throat, lymph nodes, musculoskeletal, pulmonary, and skin) during 
screening. Symptom-directed physical examination, including measurement of weight and 
height, may be performed at other time points after screening. 
6.6.2. 
Karnofsky or Lansky Performance Status Scales 
The Karnofsky score should be assessed for those aged 16 years or older, and the Lansky 
score should be assessed for those younger than 16 years (refer to Appendix B). 
6.6.3. 
Vital Signs 
Vital signs should include the following: 
x
Systolic and diastolic blood pressure (BP) (For more information on normal
ranges of BP by height and weight refer to Appendix G.)
x
Heart rate, respiratory rate, body temperature (to be collected in an
age-appropriate fashion, i.e., orally, axillary, auricularly, or rectally)
x
Height and weight (to be measured consistently without shoes using the same
instruments)
6.6.4. 
Ophthalmology Examination 
Arms 1, 2, and 3 (only patients with an optic pathway glioma [OPG] or an underlying 
visual deficit related to the primary malignancy): Ophthalmology examinations will be 
performed at baseline, at the time of radiographic assessment, and at the EOT visit as 
described in the schedule of assessments (Appendix A). The examinations will be performed 

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by an ophthalmologist or other qualified site clinical personnel (Appendix I). The 
examinations should include the following: 
x
A slit-lamp examination, specifically looking for corneal/lens abnormalities
x
A fundus examination with comment on retinal abnormalities
x
Visual fields to confrontation
x
Optic disc appearance
x
Best corrected visual acuity (BCVA) (see Section 6.9.1.2)
Arms 1, 2, and 3 (patients without an OPG or an underlying visual deficit related to the 
primary malignancy): A baseline ophthalmology examination will be performed during 
screening by an ophthalmologist or other qualified site clinical personnel. The examination 
should include the following: 
x
A fundus examination with comment on retinal abnormalities
x
BCVA (Section 6.9.1.2)
Symptom-directed examinations may be completed as needed at subsequent visits. 
Consultation with an ophthalmologist is required if abnormal ocular AEs arise as specified 
in Section 5.2.3.1. 
6.6.5. 
Dermatologic Examination 
A baseline dermatologic examination of the entire skin should be performed by the 
investigator and/or a dermatologist. The initial examination by the investigator/dermatologist 
should include a complete dermatological history of prior medications and cutaneous 
squamous cell carcinoma (SCC) risk factors (i.e., radiation therapy, sun exposure, 
immunosuppression, prior SCC, use of tanning beds, precursor lesions, and 
photochemotherapy for psoriasis). Skin lesions present at baseline should be recorded in 
medical history and only recorded as an AE if worsening of the lesion is observed. 
Subsequent examinations should be symptom-directed and as clinically indicated, and 
patients should be assessed by the investigator and/or a consulting dermatologist for skin 
lesions, especially for keratoacanthomas and squamous cell carcinomas. 
For each skin lesion observed, the dimensions and location on the body will be recorded. 
Existing lesions will be monitored throughout the study, and changes to the lesions should be 
recorded in the eCRF. Lesions developing during therapy that are suspected 
keratoacanthomas or squamous cell carcinomas will be biopsied and adequately treated; 
other lesions may be biopsied per the discretion of the investigator/dermatologist. 
6.6.6. 
Neurologic Examination 
A baseline complete neurologic examination should be performed by the investigator and/or 
a neurologist. Symptom-directed neurologic examinations may be completed at subsequent 
visits. 

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6.6.7. 
Assessment of Change in Pubertal Development  
For all arms, in patients > 8 years of age, pubertal stage will be measured according to the 
Tanner Stages before the start of treatment (screening) and yearly thereafter 
(Marshall and Tanner 1969, Marshall and Tanner 1970). For female patients, age at 
menarche will be recorded. Assessments will occur while on active treatment and during 
long-term follow-up through sexual maturity. 
6.6.8. 
Cardiac Function 
6.6.8.1. 
Electrocardiograms 
Twelve-lead resting ECGs will be performed in triplicate at baseline, with PK blood draws 
(per Table 12), and at the EOT visit. Note: there are multiple ECGs performed on C1D1, 
predose and corresponding with each PK blood draw. 
To minimize variability, it is important that patients be in a resting position for at least 
5 minutes prior to each ECG evaluation. There should be no more than 5 minutes between 
ECGs. Body position should be consistently maintained for each ECG to prevent changes in 
heart rate. ECGs for each patient should be obtained from the same machine whenever 
possible. When ECGs coincide with PK draw days, ECGs should be performed after dosing 
but before the PK blood draw. Any clinically significant changes in ECGs that occur during 
the study should be reported as AEs in the eCRF. 
6.6.8.2. 
Echocardiogram/Multiple-Gated Acquisition 
Echocardiogram or MUGA will be performed per normal site protocol. The choice of ECHO 
or MUGA is left up to the investigator, but the same technique should be used for each 
patient for each evaluation period. Any clinically significant changes in ECHO/MUGA that 
occur during the study should be reported as AEs in the eCRF. 
6.7. 
Laboratory Tests 
Routine laboratory tests, e.g., hematology and serum chemistries, will be performed locally. 
Special assessments such as PK will be performed centrally or as individually indicated. 
Additional information on the handling and processing of PK samples is provided in the 
separate Laboratory Manual. 
6.7.1. 
Pregnancy Test 
Urine or serum pregnancy tests are required for female patients of childbearing potential 
(surgically sterilized female patients or those who have not experienced menses for at least 
two years are not required to be tested). If any urine pregnancy test is positive, study 
treatment will be delayed until the patient pregnancy status is confirmed by a serum 
pregnancy test. If the serum pregnancy test is positive, the patient will be permanently 
discontinued from study treatment. Pregnancy reporting information is provided in 
Section 8.1.5. 

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6.7.2. 
Hematology 
Hematology should include assessment of the following: hemoglobin, hematocrit, red blood 
cell count, white blood cell count with differential (neutrophils [count and percentage@, 
lymphocytes, monocytes, eosinophils, and basophils [percentage@DQGSODWHOHWFRXQW 
6.7.3. 
Serum Chemistries 
Serum chemistries (nonfasting) should include assessment of the following: alkaline 
phosphatase, albumin, ALT, AST, CPK, blood urea nitrogen/urea, creatinine, glucose, lactate 
dehydrogenase, total bilirubin, total protein, sodium, potassium, chloride, phosphorus, and 
bicarbonate. 
6.7.4. 
Thyroid Function Tests 
For Arms 1 and 2 (Arm 3 required only if clinically indicated [e.g., in patients with thyroid 
cancer@), thyroid function tests should include assessment of the following: thyroid 
stimulating hormone (TSH), triiodothyronine (T3), and tetraiodothyronine (T4). Either free 
or total T3/T4 may be assessed based on local practice. 
6.8. 
Pharmacokinetic Samples: Blood 
The dose of DAY101 should be taken in the clinic on PK sampling days to ensure that a PK 
sample is collected as scheduled. Pharmacokinetic samples will be collected and handled as 
outlined in the Laboratory Manual. 
The blood sampling regimens for determining the PK of DAY101 is given in Table 12. Blood 
samples for DAY101 concentration measurements will be collected on all patients in the 
study. Exact dates and clock times of drug administration and actual PK blood draw should 
be recorded on the appropriate eCRF. If a patient experiences an AE that fits the criteria of an 
SAE as determined by the investigator, a blood sample should be collected, whenever 
possible, for measurement of drug concentrations at or around that time. 
Table 12: 
Schedule of Blood Sample Collections for DAY101 Pharmacokinetics 
Cycle 
Day 
Pharmacokinetics Timepoint 
1 
1 
1, 2, and 4 hours postdose 
1 
15 a 
A sample between 1 and 4 hours postdose 
2 
1 a 
Within 1 hour predose 
4 
1 a 
A sample between 1 and 4 hours postdose 
Every subsequent third cycle through 
C13 (e.g., C4, C7, C10, and C13) 
1 a 
A sample between 1 and 4 hours postdose 
At the time of toxicity and/or at time 
of surgery, if clinically indicated 
Unscheduled 
Random level 
At the time of a change in formulation 
(e.g., tablets to liquid, or vice versa) b 
On Day 1 of the next 
cycle following the 
formulation change 
Predose, 1, 2, and 4 hours postdose 
Abbreviation: C, Cycle. 
a ± 3-day window. 
b ECGs are not required for this assessment. 

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6.9. 
Disease Assessment 
6.9.1. 
Tumor Measurements 
Arms 1 and 2 (Low-Grade Glioma): Disease assessment must be conducted in accordance 
with the Imaging Manual. Tumors will be assessed by radiographic tumor measurements 
using MRI of the brain and spine (as indicated). 
Investigators must conform to the MRI acquisition requirements specified in the Imaging 
Manual consistently for all patients throughout the study. Disease assessments will use 
RANO criteria. 
Arm 3 (Advanced Solid Tumor): Disease assessment will be conducted using 
disease-appropriate standard-of-care imaging modalities (MRI, CT) of chest, abdomen, 
pelvis, and any other areas with suspected disease involvement, as indicated. Investigators 
must conform to the acquisition requirements specified in the Imaging Manual consistently 
for all patients throughout the study. All patients will have imaging of chest/abdomen/pelvis 
with any other areas of suspected disease involvement at baseline. Patients enrolled with a 
history of CNS metastases should additionally have a head CT or MRI scan performed at 
each tumor assessment. Investigators should use the same method consistently for an 
individual patient throughout the study. Assessments of both measurable and nonmeasurable 
disease will be made using RECIST v1.1. Patients with locally advanced soft tissue sarcoma 
should have an MRI or CT of the site of disease and a CT or X-ray of the chest, plus any 
other areas of disease involvement. 
For any patients with locally advanced disease at baseline, follow-up images can be limited 
to areas with known disease from baseline images. 
6.9.1.1. 
Collection of Radiographic Studies for Independent Review 
Baseline screening radiographic studies and all subsequent radiographic studies will be 
collected and stored for independent radiological review. In addition, prior radiographic 
scans should be submitted if acquired up to one year prior to enrollment. 
Identification of radiographic findings that may affect patient management or outcomes 
during the course of patient participation in the study are the responsibility of the treating 
physician. Independent radiology review for this trial is only used to assess the objectives of 
the study. Any unexpected medical findings identified during subsequent independent 
radiologic review will not be reported back to the investigator. 
6.9.1.2. 
Visual Acuity Assessments 
Arms 1, 2, and 3 (only patients with an OPG or an underlying visual deficit related to 
the primary malignancy): Patients who have an underlying visual function deficit related to 
the primary malignancy or OPG will have a visual acuity examination every time they have a 
radiographic disease assessment and at the EOT visit. These examinations can be performed 
by an ophthalmologist or other qualified site clinical personnel. 

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Age-specific functional visual acuity assessments should be performed, which may include, 
but are not limited to, Teller Acuity Cards® (TAC; all patients), HOTV, or other Early 
Treatment Diabetic Retinopathy Study (ETDRS) charts (in patients developmentally able to 
perform). Best corrected visual acuity and method of age-specific visual acuity testing should 
be recorded. If the BCVA data at a particular visit are felt to be unreliable due to poor 
cooperation, testing should be repeated in one to two weeks. Only the visit believed to have 
yielded the most reliable data should be reported. More details can be found in Appendix I. 
Arms 1, 2, and 3 (patients without an OPG or an underlying visual deficit related to the 
primary malignancy): A baseline ophthalmology examination will be performed during 
screening by an ophthalmologist or other qualified site clinical personnel. Symptom-directed 
examinations may be completed as needed at subsequent visits. Best corrected visual acuity 
and method of age-specific visual acuity testing should be recorded. 
6.9.1.3. 
Motor Function Evaluation Using the Vineland Motor Scale 
Arms 1 and 2 (Low-Grade Glioma): The purpose of these assessments is to document 
change in motor function from baseline, as measured by the Vineland Adaptive Behavior 
Scales, Third Edition (Vineland-3) Motor Skills domain of the Comprehensive Parent Rating 
Form. 
Parents or caregivers will be assisted by telephone in answering the parent/caregiver 
questionnaire by study personnel. The administration of the Vineland-3 is expected to take 
approximately 30 minutes to complete. It is important that the same parent who completes 
the baseline questionnaire also complete the follow-up questionnaire. 
The Vineland-3 Motor Skills questionnaire will only be administered to patients with 
baseline motor function deficits enrolled in the U.S., and only by third-party (trained and 
centralized) personnel. 
6.9.2. 
Quality of Life: Pediatric Quality of Life Inventory—Core, Cancer, and 
Patient-Reported Outcomes Measurement Information System 
In patients 2 years of age or older, Health-Related Quality of Life will be assessed using the 
Pediatrics Quality of Life™—Core (PedsQL-Core), Pediatrics Quality of Life™—Cancer 
(PedsQL-Cancer), and Patient-Reported Outcomes Measurement Information System 
(PROMIS®) assessment for the patient or parent/caregiver. 
PedsQL: 
The PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 Cancer Module will be used to 
assess treatment and disease impact on quality of life. These rating forms have 
multidimensional child self-report and parent proxy report scales to assess health-related 
quality of life (QOL) in children, adolescents, and young adults aged 2 to 25 years. It consists 
of a 23-item core measure of global QOL that has four subscales: physical functioning, 
emotional functioning, social functioning, and school functioning. 

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There are different forms for parents of patients aged 2 to 17 years (toddler: 2–4 years; young 
child: 5–7 years; child: 8–12 years; teen: 13–17 years) and parallel self-report forms for 
patients aged 5 to 25 years (young child: 5–7 years; child: 8–12 years; teen: 13–17 years; 
young adult: 18–25 years). It takes approximately 5 to 10 minutes to complete. 
PROMIS: 
The PROMIS Pediatric/Parent Proxy Profile 49 will be used to assess treatment and disease 
impact on overall health. This measure consists of seven 8-item short forms to assess mental 
health, physical health, and social health. The specific short forms are the following: 
x
Emotional Distress—Anxiety
x
Emotional Distress—Depression
x
Fatigue
x
Pain—Interference
x
Pain—Intensity
x
Physical Function—Mobility
x
Peer Relationships
Information about cognitive function will also be collected through pediatric cognitive 
supplement short form 7a. To include patients greater than 17 years of age, the PROMIS-57 
for adults, as well as adult cognitive short form 8a, will be used. 
The PROMIS® questionnaire will only be administered to English-speaking patients enrolled 
in the U.S., Australia, and U.K. 
6.10. 
Telephone/Telemedicine Visit 
The site will contact the patient or the patient’s parent/legal guardian by telephone for 
telephonic/telemedicine visits to assess for tolerability, continuation of study drug, and 
whether the patient needs to return to clinic earlier than planned. If not tolerating the drug 
well, the patient should be seen at least every seven days to assess AEs, and the patient or the 
patient’s parent/legal guardian should be contacted regularly to assess AE status. 
6.11. 
Survival Status 
Patients will be followed for survival status and subsequent anticancer therapies by telephone 
or any other method. 
6.12. 
Study Drug Administration and Dosing Diary 
Completion of the outpatient dosing diary will include recording of DAY101 dosing. 
Special considerations: Patients who enter a “drug holiday” discontinuation period after 
Cycle 26 may be considered for resumption of study drug if there is disease recurrence. As 
such, these patients should continue radiographic and/or clinical assessment of disease 

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response using the same modality and frequency used during the treatment portion of the 
study. These response assessments should be collected and reported every three months. 
These patients remain on study and will not have an EOT visit until death, loss of follow-up, 
withdrawal of consent, initiation of a new anticancer therapies, or study termination. The 
EOT visit will only occur once per patient. 
6.13. 
Concomitant Medication 
All medications that were used from 28 days prior to enrollment through the end of study 
participation will be recorded in the eCRF. 
6.14. 
End of Treatment Visit 
End of treatment is defined as Day 28 (± 7 days) of the final cycle of treatment (or time of 
premature discontinuation of treatment if clinically feasible). The EOT assessments and 
procedures will be conducted in accordance with the schedule of assessments (Appendix A). 
6.15. 
Safety Follow-Up Visit 
Safety follow-up assessments may be performed as part of the EOT visit if the latter was 
performed at least 28 days after final dose of the last cycle. The safety follow-up visit may be 
conducted by telephone if patient is not able to return to clinic. 
The status of unresolved AEs should be assessed at the safety follow-up visit. 
6.16. 
Long-Term Follow-Up 
After permanent early treatment discontinuation, long-term follow-up assessments will occur 
approximately every three months (± 1 month) until the patient withdraws consent for further 
participation, is lost to follow-up, has died, or the study is closed. Patients who discontinue 
treatment due to a reason other than disease progression will continue radiographic tumor 
assessments per the protocol. 
For patients in long-term follow-up with radiographic evidence of disease progression (or 
those unable to continue tumor assessments), the site will contact the patient or the patient’s 
parent/legal guardian for follow-up assessments that may include subsequent anticancer 
therapies and survival status. Long-term follow-up may be conducted by telephone. For any 
patient who is lost to follow-up, the study site will attempt to ascertain survival information 
via public database search. If survival status still cannot be ascertained, patients will be 
considered lost to follow-up and will be censored appropriately. The first long-term 
follow-up assessment will occur three months (± 1 month) after the EOT visit. 
6.17. 
Force Majeure Flexibility 
With the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 
the impact of coronavirus disease 2019 (COVID-19) on the health-care system, the Sponsor 
of this study recognizes the need for flexibility in ensuring access to therapy. This need has 
been clearly elucidated in the FDA Guidance on Conduct of Clinical Trials of Medical 
Products during COVID-19 Public Health Emergency (FDA-2020-D-1106) and the EMA 

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Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) 
pandemic (Version 3, 28/04/2020). While every effort should be made to follow the timing of 
study visits and procedures as closely as possible, the Sponsor may introduce flexibility in 
the nature and timing of visits. Changes may include using home health-care visits, 
telemedicine visits, local imaging, and distribution of multiple cycles of investigational 
product (or shipping investigational product to a patient’s residence). 
If such flexibility needs to be implemented for the safe conduct of this study, the Sponsor 
will notify sites of what procedures may be delayed or provide flexibility in how data are 
collected. As potential impacts to the health-care system may not be uniform through all 
regions where the Sponsor is conducting this study, guidance will be informed by worldwide 
regulatory authority guidance and local competent and ethical authorities, and may vary from 
site to site. Changes to timing and procedures will be communicated by the Sponsor through 
an official memo and training. 
Visits occurring on C1D1, C1D15, and C2D1 must occur within specified protocol window 
for all patients enrolled. Visits held in conjunction with a response assessment must also 
occur in person, within the specified window. At a minimum, height and weight, chemistry, 
hematology, liver function tests, CPK, AEs, concomitant medications, ECGs, and imaging 
studies need to be collected. If needed, the use of a local hospital laboratory or commercial 
laboratory (e.g., LabCorp, Quest, etc.), may be used, if results can be provided to the treating 
physician prior to the visit. Imaging at a qualified MRI facility closer to the patient’s 
residence may be used following training by the imaging vendor, with all imaging data 
submitted to the Sponsor. Following the C2D1 visit, windows around study visits and 
assessments may be expanded up to ± 7 days. For patients with a confirmed RANO response 
without clinical signs of progressive disease, imaging may occur up to seven days after the 
planned cycle visit date. 
7.
PLANNED ANALYSES
The Statistical Analysis Plan provides specific details on the analytical methods and data 
displays. 
7.1. 
Analysis Populations 
The populations for analysis are defined in Table 13: 

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Table 13: 
Population Definitions 
Population 
Description 
Evaluable 
Evaluable for Efficacy (FAS): All patients enrolled in the study who 
received at least 1 dose of study treatment and meet the definition for 
Efficacy Analysis as outlined in Section 7.3.1 
Evaluable for DOR: Patients in the FAS who have a best overall confirmed 
response of CR or PR 
Safety 
All patients enrolled in the study who received at least 1 dose of study 
treatment (SAS) 
Abbreviations: CR, complete response; DOR, duration of response; FAS, Full Analysis Set; ICF, informed 
consent form; PR, partial response; SAS, Safety Analysis Set. 
7.2. 
Determination of Sample Size 
Arm 1 (Low-Grade Glioma): A sample size of 60 patients provides 88% power to reject the 
null ORR of 21%, assuming that the true underlying ORR of DAY101 is 40% based on a test 
at the 2-sided 0.05 level. A result of at least 20 out of 60 (0.33) will be statistically 
significant. 
A Phase 2 study of single-agent vinblastine (Bouffet et al. 2012), the largest study published 
to date in patients with relapsed or refractory low-grade glioma, reported objective responses 
(CR + PR) in 11 of 48 patients (ORR: 23% [95% CI: 12–@). This response rate 
represents the anticipated RANO ORR applied to this dataset (CR + PR, but not minor 
responses). 
Arm 2 (Low-Grade Glioma Extension): Up to approximately 60 patients may be enrolled. 
Arm 2 is not powered based on formal statistical hypothesis testing, but for practical 
considerations to allow patients with pediatric low-grade glioma to receive treatment with 
DAY101 after Arm 1 has fully accrued and the DSMB has recommended opening to 
enrollment. 
Arm 3 (Advanced Solid Tumor): Up to approximately 20 patients may be enrolled to 
provide a preliminary evaluation of DAY101 in pediatric patients with advanced solid 
tumors. For this portion of this study, a modified Simon 2-stage design will be used to enroll 
up to approximately 20 patients based on evaluation of ORR (confirmed PR or CR per 
RECIST v1.1) (Simon 1989). The statistical assumptions will require approximately 12 
evaluable patients in the first stage and 20 evaluable patients in total. In the first stage, if  1 
objective response (PR or CR per RECIST v1.1) is seen in the first 12 patients, the study will 
stop any further recruitment and the treatment will be considered as not effective in this 
setting; however, if  2 objective responses occur, an additional eight patients will be 
recruited. The anticipated response rate is expected to be near zero in patients with relapsed 
or progressive advanced solid tumors that have progressed after standard-of-care therapy and 
harbor an activating driver alteration. However, for the purposes of sample size calculation, a 
null hypothesis (H0) of 5% is assumed. A sample size of 20 patients provides 90% power to 
reject the null ORR of 5%, assuming that the true underlying ORR of DAY101 is 25% based 

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on a test at alpha 1-sided at 0.1. A result of at least three out of 20 will be statistically 
significant. 
7.3. 
Statistical Methods 
7.3.1. 
Efficacy Analyses 
7.3.1.1. 
Arm 1: Low-Grade Glioma 
The efficacy analyses will include all patients who received at least one dose of study drug 
and have measurable disease as determined by the IRC at baseline and have follow-up 
imaging or radiographically confirmed progressive disease prior to the first imaging 
timepoint (Arm 1 Full Analysis Set >)$6@). Patients who do not meet this criterion (e.g., lost 
to follow-up with no follow-up imaging) will be replaced. Some efficacy analyses may be 
performed with one or more tumor types combined (e.g., subgroup of Arm 1 FAS consisting 
of patients with BRAF V600 mutation vs. BRAF fusion). 
Primary Endpoint: 
Overall response rate will be calculated by the number of patients with best overall 
confirmed response of CR or PR as determined by an IRC using RANO criteria among 
patients in the Arm 1 FAS. All responses will be confirmed by a second scan  28 days after 
the initial response. An exact binomial test will be used to compare the observed response 
rate to the hypothesized null ORR of 21%, and a 95% CI will be calculated using the 
Clopper-Pearson method. 
Secondary Endpoints: 
Clinical efficacy in antitumor activity will be assessed as the following secondary endpoint 
efficacy outcome measures: 
Overall response rate will be calculated by the number of patients with best overall 
confirmed response of CR or PR as determined by the treating investigator using the RANO 
criteria among patients in FAS. 
Overall response rate will be calculated by the number of patients with best overall 
confirmed response of CR or PR as determined by an IRC using RAPNO–low-grade glioma 
criteria among patients in FAS. 
Best overall response (BOR) is defined as the best response (CR, PR, minor response, SD, 
SURJUHVVLYHGLVHDVH>3'@, not evaluable [NE@, and unknown) recorded from the start of the 
treatment until disease progression/recurrence or death (taking the smallest measurements 
recorded since the treatment started as a reference for PD). The patient’s best response 
assignment will depend on the achievement of both measurement and confirmation criteria. 
The first disease assessment will occur at approximately 12 weeks post-treatment. Response 
assessment will continue until progression or death. If a patient is given antitumor treatment 
(anticancer surgery/procedure, anticancer radiotherapy, and anticancer systemic therapy other 

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than the study treatment) prior to PD or death, determination of BOR will be calculated using 
tumor assessment responses up to the date of the last tumor assessment prior to the start date 
of the antitumor treatment. 
The DOR will be evaluated in patients with BOR of CR or PR based on RANO and RAPNO 
criteria as determined by 1) an IRC and 2) the treating investigator (RANO only). Duration 
of response is measured by the length of response in FAS patients with best overall 
confirmed response of CR or PR using RANO criteria. 
The length of response is defined as the time from the first date of a patient’s best overall 
objective response until the time of disease progression using RANO and RAPNO criteria as 
determined by 1) an IRC and 2) the treating investigator (RANO only).  
The duration of PFS will be evaluated in FAS based on RANO and RAPNO criteria 
following initiation of DAY101 as determined by 1) an IRC and 2) the treating investigator 
(RANO only). Progression-free survival is measured by the time following initiation of 
DAY101 to progression or death in patients treated with DAY101, whichever occurs first. 
The TTR will be evaluated in FAS patients with response of CR or PR following initiation of 
DAY101 based on RANO and RAPNO criteria as determined by 1) an IRC and 2) the 
treating investigator (RANO only). Time to response is measured by the time to the first 
response following initiation of DAY101 in FAS patients with best overall confirmed 
response of CR or PR. 
The clinical benefit rate will be evaluated based on the proportion of patients with BOR of 
CR, PR, MR, or SD in FAS. The BOR will be defined by RANO and RAPNO criteria, 
lasting 12 months or more following initiation of DAY101 as determined by 1) an IRC and 
2) the treating investigator (RANO only).
Overall survival is defined as the date of enrollment to the date of death. Overall survival in 
monWKVZLOOEHFDOFXODWHGDVGHDWKGDWHíHQUROOPHQWGDWH• (12/365.25). Censoring will 
occur as if there is no confirmation of death. Overall survival will be censored on the date 
that the patient is last known to be alive. 
7.3.1.2. 
Arm 2: Low-Grade Glioma Extension 
Where appropriate (e.g., in patients with measurable disease), patients will be evaluated via 
the same statistical methods as described for Arm 1. 
7.3.1.3. 
Arm 3: Advanced Solid Tumor 
The efficacy analyses will include all patients who received at least one dose of study drug, 
have measurable disease as determined by the IRC at baseline, and have follow-up imaging 
or radiographically confirmed progressive disease prior to the first imaging timepoint (Arm 3 
FAS). Patients who do not meet this criterion (e.g., lost to follow-up with no follow-up 

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imaging) will be replaced. These analyses may be summarized by tumor type, and some 
efficacy analyses may be performed with one or more tumor types combined. 
Primary Endpoint: 
The estimate of the ORR will be calculated by the number of patients with best overall 
confirmed response of CR or PR as determined by an IRC using RECIST v1.1 criteria among 
the Arm 3 FAS. All responses will be confirmed by a second scan t 28 days after the initial 
response. The estimate of the ORR will be accompanied by 1- and 2-sided CIs with various 
coverage probabilities (e.g., 80%, 95%). The primary analysis of ORR will be based on the 
responses determined by an IRC. A secondary analysis will be based on the treating 
investigator’s assessment. 
Secondary Endpoints: 
Clinical efficacy will also be assessed by the following secondary endpoint efficacy outcome 
measures: 
Overall response rate will be calculated by the number of patients with best overall 
confirmed response of CR or PR as determined by the treating investigator using RECIST 
v1.1 criteria among patients in FAS. 
Best overall response is defined as the best response (CR, PR, SD, PD, NE, and unknown) 
recorded from the start of the treatment until disease progression/recurrence or death (taking 
the smallest measurements recorded since the treatment started as a reference for PD). The 
patient’s best response assignment will depend on the achievement of both measurement and 
confirmation criteria. The first disease assessment will occur at approximately eight weeks 
post-treatment. Response assessment will continue until progression or death. If a patient is 
given antitumor treatment (anticancer surgery/procedure, anticancer radiotherapy, and 
anticancer systemic therapy other than the study treatment) prior to PD or death, 
determination of BOR will be calculated using tumor assessment responses up to the date of 
the last tumor assessment prior to the start date of the antitumor treatment. 
Best overall response, PFS, TTR, CBR, and OS will be evaluated as defined above (per 
RECIST v1.1, as applicable). 
7.3.2. 
Safety Analyses 
Safety will be assessed by clinical review of all relevant parameters, including AEs, SAEs, 
laboratory values, and vital signs. Unless specified otherwise, the safety analyses will be 
conducted for the safety population defined in Section 7.1. 
Summary tables and listings will be provided for all reported TEAEs, defined as AEs that 
start on or after the first administration of study drug. The reported AE term will be assigned 
a standardized Preferred Term using the Medical Dictionary for Regulatory Activities 
(MedDRA), version 17.1 or later. 

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7.3.2.1. 
Deaths 
All deaths on study should be reported and recorded on the Death CRF page and should 
include the date and cause of death. Deaths will be reported in a patient listing and will 
include the primary cause of death and the number of days between the date of the last dose 
of study drug and death. 
7.3.2.2. 
Laboratory Values 
Laboratory values will be assigned toxicity grades when available using the NCI CTCAE, 
version 5.0 or later. Directional shifts in laboratory toxicity grades (comparing baseline grade 
with worst postbaseline grade) will be analyzed using standard shift tables, presenting 
number and proportion of patients and their maximum grade shift. For analytes without a 
toxicity grading scale, the shift table will present directional shifts from baseline to above or 
below the laboratory standard normal range using the maximum increase and/or decrease 
observed throughout the course of treatment/observation. 
7.3.2.3. 
Vital Signs 
All patients will have pretreatment baseline vital signs and predose measurements as 
described in Appendix A. The results for each vital sign will be summarized in a descriptive 
manner by calculating the mean, standard deviation, median, and range by time point in the 
same manner described for laboratory values. For these analyses, the minimum, maximum, 
average, and last postbaseline value will be determined relative to the baseline vital sign 
measurements only. The Wilcoxon signed rank test may be used to assist in the identification 
of any systematic changes. 
7.3.2.4. 
Concentration QTc (cQTc) Analysis 
All patients who received at least one dose of DAY101 and had at least one pair of evaluable 
ǻ47F) and DAY101 plasma concentration at any postdose time point. This will be the 
SULPDU\DQDO\VLVVHWIRUH[SORULQJWKHUHODWLRQVKLSEHWZHHQǻ47FLQWHUYDOVDQGSODVPD
concentrations of DAY101. The relationship between ǻ47F) and the plasma concentrations 
of DAY101 may be investigated in an exploratory manner and will be reported in a 
standalone document. 
7.3.2.5. 
Concomitant Medications 
Prior and concomitant medications will be coded to the generic term using the current 
version of the WHO Drug Dictionary and listed by patient. 
7.3.2.6. 
Pharmacokinetic Analyses 
Plasma concentrations of DAY101 will be determined with a validated bioanalytical assay. 
The following PK parameters may be calculated where appropriate: Cmax, minimum drug 
concentration (Cmin), Cave, time at which maximum observed concentration occurs (Tmax), 
AUC from time zero to t (AUC0–t), and apparent oral clearance of drug (CL/F). 
Summary statistics will be generated as appropriate. 

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7.3.3. 
Health-Related Quality of Life 
Changes in quality-of-life measures from baseline will be evaluated for patients  2 years of 
age or older using the PedsQL-Core, PedsQL-Cancer, and PROMIS® assessment. The 
PROMIS® questionnaire will only be administered to English-speaking patients enrolled in 
the U.S., Australia, and U.K. Longitudinal changes in quality-of-life scores from baseline 
will be summarized in a descriptive manner. 
7.3.4. 
Visual Acuity Outcomes 
Arms 1 and 2 (Low-Grade Glioma): Visual acuity (VA) progression is defined as a 
decline  0.2 logMAR (corrected for age). Visual acuity response is DQLPSURYHPHQWRI 0.2 
logMAR (corrected for age). 
Summary statistics will be generated as appropriate. 
7.3.5. 
Motor Function (Vineland) Outcomes 
Arms 1 and 2 (Low-Grade Glioma): Change in the Vineland-3 Motor Skills domain from 
baseline will be evaluated after one and two years of treatment. The Vineland-3 Motor Skills 
questionnaire will be administered to patients with baseline motor function deficits at U.S. 
sites only. 
Summary statistics will be generated as appropriate. 
8.
SAFETY
8.1. 
Adverse Events and Serious Adverse Events 
All AEs, whether reported by the patient or the patient’s parent/legal guardian or noted by 
study personnel, will be recorded in the patient’s medical record on the Adverse Event eCRF. 
See Appendix J for instructions on collecting, assessing, and reporting of AEs. 
8.1.1. 
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information 
Report only SAEs deemed related to protocol-mandated procedures from the signing of 
informed consent through to start of treatment with DAY101. 
Report all AEs, including SAEs, from the start of treatment with DAY101 until 30 days after 
the last dose of DAY101. 
After 30 days post–treatment discontinuation, report any targeted SAEs (e.g., neurological 
disorders, autoimmune disorders, ocular disorders, cardiac disorders, and secondary 
malignancies) observed by the investigator or reported by the patient, regardless of causality 
to study drug. In addition, report any SAEs considered related to DAY101. 

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For patients who screen fail or are enrolled, but do not receive DAY101, the reporting 
period for SAEs ends 30 days after the last procedure (e.g., screening procedure). 
Table 14: 
Summary of Adverse Event Collection Periods 
Time Period 
AE Collection 
ICF signature prior to first dose of DAY101 
Protocol/procedure-related SAEs only 
DAY101 to 30 days after last study drug dose 
All AEs and SAEs 
Beyond 30 days after last study drug dose 
(DAY101) 
Targeted SAEs (e.g., neurological disorders, autoimmune 
disorders, ocular disorders, cardiac disorders, and 
secondary malignancies), regardless of causality to study 
drug 
Any SAEs related to DAY101 
Abbreviations: AE, adverse event; ICF, informed consent form; SAE, serious adverse event. 
Report and record all SAEs to the Sponsor or designee within 24 hours following the 
investigator’s knowledge of the events, as indicated in Appendix J. The investigator will 
submit any updated SAE data to the Sponsor within 24 hours of their being available. 
If the investigator learns of any SAE, including a death, at any time after a patient has been 
discharged from the study, and he/she considers the event to be reasonably related to the 
study intervention or study participation, the investigator must promptly notify the Sponsor. 
8.1.2. 
Method of Detecting Adverse Events and Serious Adverse Events 
The method of recording, evaluating, and assessing causality of AE and SAE and the 
procedures for completing and transmitting SAE reports are provided in Appendix J. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the patient or the patient’s parent/legal guardian is the 
preferred method to inquire about AE occurrences. 
8.1.3. 
Follow-Up of Adverse Events and Serious Adverse Events 
After the initial AE/SAE report, the investigator is required to proactively follow each patient 
at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the 
event is otherwise explained, or the patient is lost to follow-up. Further information on 
follow-up procedures is provided in Appendix J. 
If a patient begins a new anticancer therapy, the AE reporting period for non-SAEs ends at 
the time the new treatment is started. 
8.1.4. 
Regulatory Reporting Requirements for Serious Adverse Events 
Any SAEs occurring during this study must be reported as follows: 
x
Prompt (within 24 hours of awareness) notification by the investigator to the
Sponsor of an SAE is essential so that legal obligations and ethical responsibilities

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toward the safety of patients and the safety of a study intervention under clinical 
investigation are met. Serious Adverse Events should be reported to the Sponsor 
via email at safetyreporting@dayonebio.com. 
x
The Sponsor has a legal responsibility to notify both the local regulatory authority
and other regulatory agencies about the safety of a study intervention under
clinical investigation. The Sponsor will comply with country-specific regulatory
requirements relating to safety reporting to the regulatory authority, Institutional
Review Boards (IRB)/Independent Ethics Committees (IEC), and investigators.
x
An investigator who receives an investigator safety report describing an SAE or
other specific safety information (e.g., summary or listing of SAEs) from the
Sponsor will review and then file it along with the IB and will notify the IRB/IEC,
if appropriate, according to local requirements.
8.1.5. 
Pregnancy
There is no relevant clinical experience with DAY101 in pregnant or lactating female
patients, and animal reproductive studies have not been performed. Female patients of
childbearing potential must have a negative pregnancy test prior to enrollment because of the
potentially dangerous effects of the preparative chemotherapy on the fetus. This experimental
therapy should not be administered to pregnant women or women who are breastfeeding.
x
Details of all pregnancies in female patients and female partners of male patients
will be collected for pregnancies occurring after the start of study intervention
until six months after completing DAY101.
x
If a pregnancy is reported, the investigator should inform the Sponsor within
24 hours of learning of the pregnancy and should follow the procedures outlined
in Appendix K.
x
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth,
congenital anomalies, ectopic pregnancy) are considered SAEs.
x
Details of all lactation cases in female patients will be collected while taking
protocol-required therapies.
x
If a lactation case is reported, the investigator should inform the Sponsor within
24 hours of learning of the lactation case and should follow the procedures
outlined in Appendix K.
In addition to reporting any pregnancies or lactation cases occurring during the study, 
investigators should monitor for pregnancies or lactation cases that occur after the last dose 
of DAY101 through six months for female patients and for six months for female partners of 
male patients. 
8.1.6. 
Deaths 
Deaths occurring during the AE reporting period, regardless of attribution to DAY101, will 
be recorded as an AE and expeditiously reported to the Sponsor. However, deaths clearly 
attributed to underlying progression of malignancy do not need to be reported as SAEs. 

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8.5. 
Grading and Intensity of Adverse Events 
The investigator will grade the severity of each AE using, when applicable, the NCI CTCAE, 
version 5.0. In the event of an AE for which no grading scale exists, the investigator will 
classify the AE as mild, moderate, severe, life-threatening/debilitating, or fatal, as defined in 
Table 15. 
Table 15: 
NCI CTCAE Definitions of Severity for Adverse Reactions 
Toxicity 
Grade / Details 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; no interventions 
required 
(an event that is usually transient in nature and generally not interfering with normal activities) 
Grade 2 
Moderate; minimal, local, or noninvasive intervention indicated; some limitation of activities 
(an event that is sufficiently discomforting to interfere with normal activities) 
Grade 3 
Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization required; disabling; limitation of patient’s ability to care for 
him/herself 
(an event that is incapacitating with inability to work or do usual activity, or inability to work or 
perform normal daily activity) 
Grade 4 
Life-threatening consequences; urgent intervention required 
(an event that puts the patient at immediate or potential risk of death, requires hospitalization, or which 
drastically impacts a patient’s well-being) 
Grade 5 
Death related to adverse event (fatal) 
Abbreviations: NCI CTCAE, National Cancer Institute-Common Terminology Criteria for Adverse Events. 
8.6. 
Relationship to Study Drug 
The investigator will categorize each AE as to its potential relationship to investigational 
product using the categories of Yes (causally related) and No (unrelated), as defined below. 
The assessment of the relationship of an AE to the administration of investigational product 
is a clinical decision based on all available information at the time. 
No: 
The time course between the administration of study drug and the occurrence or worsening of 
the AE rules out a causal relationship, and another cause (concomitant drugs, therapies, 
complications, comorbidities, etc.) is suspected. 
Yes: 
A causal relationship between medicinal product and an AE is at least a reasonable 
possibility. The AE cannot reasonably be explained by the subject’s clinical state, 
concomitant medical condition or concomitant therapies, and a temporal relationship exists 
between the event onset and administration of the study drug. 
An unexpected AE is an experience not previously reported or an AE that occurs with 
specificity, severity, or frequency that is not consistent with the current DAY101 IB. 

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8.7. 
Serious Adverse Event Follow-Up 
For all SAEs occurring during the study, the investigator must submit follow-up reports to 
the Sponsor regarding the status of the SAE and the patient’s subsequent course until the 
SAE has resolved, the condition stabilizes or is deemed chronic (in the case of persistent 
impairment), the patient or the patient’s parent/legal guardian withdraws consent for further 
follow-up, or the patient dies. 
9.
STUDY ADMINISTRATION
9.1. 
Regulatory and Ethical Considerations 
9.1.1. 
Regulatory Authority Approval 
This study will be conducted in accordance with the International Council for Harmonisation 
guidelines for Good Clinical Practices (ICH-GCP (>5@), an international ethical and 
scientific quality standard for designing, conducting, recording, and reporting studies that 
involve human patients. All applicable country and local regulations will also be observed; 
these include the provisions of the German Medicinal Products Act (Arzneimittelgesetz 
>$0*@WKH2UGLQDQFHRQWKHLPSOHPHQWDWLRQRI*RRG&OLQLFDO3UDFtice in the conduct of 
clinical trials on medicinal products for use in humans (GCP-V), as well as the General Data 
Protection Regulation 2016/679 (GDPR) and the German Federal Data Protection Act 
(Baden-:UWWHPEHUJ6WDWH'DWD3URWHFWLRQ$FW>%'6*@6WDWHData Protection Act of 
Baden-Württemberg (LDSG BW). Compliance with these standards provides assurance that 
the rights, safety, and well-being of study patients are protected, consistent with the 
principles in the Declaration of Helsinki, and that the clinical study data are credible. 
9.1.2. 
Ethics Approval 
It is the responsibility of the investigator to ensure that the appropriate IRB/ Research Ethics 
Board (REB)/IEC/ Human Research Ethics Board (HREC) has reviewed and approved this 
protocol prior to initiating the study. The investigator must provide the Sponsor or Sponsor’s 
representative with current and revised IRB/REB/IEC/HREC membership rosters that 
include the members’ occupations and qualifications or provide a copy of the US Department 
of Health and Human Services Assurance Number. 
The IRB/REB/IEC/HREC must also review and approve the clinical site’s ICF, pediatric 
assent form, other written information provided to the patient, and all advertisements that 
may be used for patient recruitment. The investigator will provide the study monitor with 
copies of these documents and of dated IRB/REB/IEC/HREC approval(s) prior to the start of 
the study. 
The IRBs/REBs/IECs/HREC are required to determine whether child assents are appropriate 
for all studies that include pediatric patients. The IRB/REB/IEC/HREC may opt to waive 
assent if the patients are not capable of understanding (e.g., based on level of intellectual 
development or maturity) or if the study is in the best interest of the patient (i.e., strong 

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possibility of benefit and no other alternatives are available). If an IRB/REB/IEC/HREC 
chooses to waive assent, this must be documented in the IRB/REB/IEC/HREC approval 
letter. 
If the protocol or the ICF or pediatric assent form is amended during the study, the 
investigator is responsible for ensuring that the IRB/REB/IEC/HREC has reviewed and 
approved these amended documents. Approval of the amended documents must be obtained 
from the IRB/REB/IEC/HREC before implementation and before new patients are consented 
to participate in the study using the amended version of the ICF/pediatric assent form. The 
investigator must provide the Sponsor with the dated IRB/REB/IEC/HREC approval of the 
amended documents as soon as available. 
9.1.3. 
Patient Informed Consent and Pediatric Assent 
The investigator and designated site staff who will perform the consent/assent process are 
responsible for knowing country-specific regulations and other local requirements with 
regard to child assent to ensure that the assent process is conducted in accordance with those 
requirements. Prior to study entry, the investigator or designee will explain the nature, 
purpose, benefits, and risks of participation in the study to each patient and the patient’s 
legally acceptable representative, legal guardian, or impartial witness. Written informed 
consent and pediatric assent, where applicable, must be obtained prior to the patient’s 
entering the study (before initiation of any study-related screening procedure). In pediatric 
cases, where applicable and according to local regulations, both parents may be required to 
sign informed consent. Sufficient time will be allowed to discuss any questions raised by the 
patient. The ICF/pediatric assent form, which will contain all US federally-required elements, 
all ICH-required elements, and Health Insurance Portability and Accountability Act 
authorization information in a language that is understandable to the patient, must be signed 
by all patients, or by the patient’s legal representative. The process of obtaining the ICF and 
pediatric assent form, where applicable, will be in compliance with all applicable local and 
country regulations and ICH requirements. 
The pediatric assent form must have a date and signature line for the child. State laws differ 
in their requirements for patients who have not reached the legal age of majority and 
IRBs/REBs/IECs/HRECs are responsible for following their local regulations. Use of an 
assent is not a substitute for parental permission. Parents/guardians must receive a full ICF to 
review and sign. 
If the ICF and pediatric assent form, where applicable, is amended during the study, the 
investigator must follow all applicable regulatory requirements pertaining to 
IRB/REB/IEC/HREC approval of the amended form. The clinical site must use the amended 
ICF/pediatric assent form for all new patients and repeat the consent/assent process with the 
amended form for any ongoing patients. 
An initial ICF (for adult patients or parent/guardian of child/adolescent patients) and 
pediatric assent form (for child/adolescent patients, as applicable) will be provided to the 

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investigator to prepare the ICF and assent documents to be used at the Principal 
Investigator’s site. The sample ICFs/pediatric assent forms prepared by the Sponsor are 
provided in the Study Manual. 
9.1.4. 
Investigator Reporting Requirements 
In accordance with applicable regulatory requirements, the investigator is solely obligated to 
inform the IRB/REB/IEC/HREC of progress of the study and notify the 
IRB/REB/IEC/HREC of study closure. The investigator must also provide the Sponsor with 
copies of all IRB/REB/IEC/HREC correspondence that relate to study approvals, updates, or 
changes. The investigator is also responsible for forwarding to the IRB/REB/IEC/HREC 
reports of any SAEs from other studies conducted with the same investigational product that 
were provided by the Sponsor. 
9.2. 
Data Management 
Data will be recorded at the site on source documents and reviewed by the Sponsor’s site 
monitor, who will verify data recorded in the eCRFs with source documents, during periodic 
visits. All corrections or changes made to any study data must be appropriately tracked in an 
audit trail in the eCRF system. The eCRFs will be considered complete when all missing, 
incorrect, and/or inconsistent data have been accounted for. Additional instructions on eCRF 
completion are provided in the electronic data capture (EDC) Manual. eCRFs should be 
entered within 5 to 10 business days of each visit and all queries should be answered within 5 
to 10 business days of receipt. 
All eCRFs must be reviewed and signed by the investigator. 
9.3. 
Study Monitoring 
Prior to the start of the study, the Sponsor’s monitor or designee will contact the clinical site 
to discuss the protocol and data collection procedures and conduct applicable training of site 
personnel. The Sponsor and its designees will also periodically contact the clinical site during 
the conduct of the study (which will include remote and on-site visits) in accordance with 
applicable regulations and GCP. During these contacts, the monitoring activities will include 
the following: 
x
Checking and assessing the progress of the study
x
Reviewing study data collected to date for completeness and accuracy
x
Conducting source document verifications by reviewing each patient’s eCRF
against source documents
x
Identifying any issues and addressing resolutions
x
Recording and reporting protocol deviations not previously reported to the
Sponsor
x
Confirming that SAEs have been properly reported to the Sponsor and submitted
to the IRB/REB/IEC/HREC if appropriate

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These activities will be done in order to verify that the data are authentic, accurate, and 
complete; that the safety and rights of the patient are being protected; and that the study is 
conducted in accordance with the currently approved protocol, GCP, and all applicable 
regulatory requirements. Additionally, to ensure compliance with GCP and all applicable 
regulatory requirements, the Sponsor or designee may conduct a quality assurance audit. 
9.4. 
Termination 
Upon completion of the study, the following activities, when applicable, must be conducted 
by the study monitor and the investigator: 
x
Submission of all study data to the Sponsor
x
Completion of all data clarifications and/or resolutions
x
Reconciliation and final disposition of investigational product
x
Review of site study files for completeness
In addition, the Sponsor reserves the right to temporarily suspend or prematurely terminate 
this study for any reason. 
If the study is suspended or terminated for safety reasons, the Sponsor will promptly inform 
the investigator, and will also inform the IRB/REB/IEC/HREC with the reasons for the 
action. In the event of prematurely termination, all study data must be submitted to the 
Sponsor. In addition, the clinical site must document final disposition of all unused 
investigational product in accordance with the Sponsor’s procedures. 
9.5. 
Records Retention 
Patient records, source documents, monitoring visit logs, investigational product inventory, 
regulatory documents, and other correspondence pertaining to the study must be maintained 
in the appropriate site study files according to ICH GCP and applicable regulatory 
requirement(s). Records will be retained for at least two years after the last marketing 
application approval or two years after formal discontinuation of the clinical development of 
the investigational product or according to applicable regulatory requirement(s). If the 
investigator withdraws from the responsibility of keeping the study records, custody must be 
transferred to a person willing to accept the responsibility. The Sponsor must be notified 
immediately by telephone or e-mail and the notification confirmed in writing if a custodial 
change occurs. 
9.6. 
Confidentiality of Information 
Patient names will remain confidential and will not be supplied to the Sponsor or its 
designee. The investigator will maintain a personal patient identification list (patient and 
treatment numbers with the corresponding patient names) to enable records to be identified. 

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10.
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Appendix A: 
Study Assessments 
Table 16: 
Arms 1 and 2 Schedule of Assessments 
Assessment 
Pre-
Enrollment 
Post-Enrollment 
Visit 
Day 
(Time Window) 
Screening a 
(Pre-First 
Dose) 
GD\V 
Cycle 1 
Cycles 
2–26 
(± 3 days) 
Cycle 27 – EOT (± 3 days) 
EOT 
Visit 
(±7 days) 
30-Day
Post-EOT 
Safety 
Follow-Up 
(±14 days) 
LTFU 
Every 
3 ± 1 mo d 
Day 1 b 
(Pre-
Dose) 
Day 8 
(± 3 
days) 
Day 15 
(± 3 
days) 
Day 22 
(± 3 
days) 
On Drug 
Therapy c 
Drug 
Holiday 
Informed consent/assent 
X e 
Demographics, medical, surgical, and 
cancer history (including prior 
12 months of scans, date of 
progression, best response, and DOR 
from prior therapies, and tolerability 
of prior therapy, if available) 
X 
Confirmation that archival tumor 
tissue sample is available f 
X 
Physical examination g 
X 
X 
X 
X 
X 
X 
X 
Neurological examination g 
X 
X 
X 
X  
X 
X 
X 
Dermatologic examination incl. 
suspicious lesions g 
X 
X 
X 
X  
X 
X 
X 
Ophthalmology examination h 
X 
Perform every time tumor assessments are done.  
X  
X 
Visual acuity testing i 
X 
Perform every time tumor assessments are done. 
X 
X 
Tanner Stages j 
X 
C13D1 and 
C27D1 
Once yearly 
Once 
yearly 
Vital signs incl. height and weight 
X 
X 
X 
X k 
X 
X 
X 

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Assessment 
Pre-
Enrollment 
Post-Enrollment 
Visit 
Day 
(Time Window) 
Screening a 
(Pre-First 
Dose) 
GD\V 
Cycle 1 
Cycles 
2–26 
(± 3 days) 
Cycle 27 – EOT (± 3 days) 
EOT 
Visit 
(±7 days) 
30-Day
Post-EOT 
Safety 
Follow-Up 
(±14 days) 
LTFU 
Every 
3 ± 1 mo d 
Day 1 b 
(Pre-
Dose) 
Day 8 
(± 3 
days) 
Day 15 
(± 3 
days) 
Day 22 
(± 3 
days) 
On Drug 
Therapy c 
Drug 
Holiday 
12-lead ECG in triplicate  l 
X 
X 
pre-
dose 
and 
with 
each 
PK 
blood 
draw 
X 
C2D1, 
C4D1, and 
every 3rd 
cycle 
through 
C13 
(C7D1, 
C10D1, and 
C13D1) 
X 
Echocardiogram/MUGA m 
X 
C2D1, 
C4D1, and 
every 3rd 
cycle 
(C7D1, 
C10D1, 
etc.) 
X 
X 
Creatine phosphokinase 
X 
C2D1, 
C4D1 and 
every 4th 
cycle 
(C8D1, 
C12D1, 
etc.) 
X 
X 
Hematology and chemistry 
X 
X  n, o 
X 
X k 
X 
X 
X 

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Assessment 
Pre-
Enrollment 
Post-Enrollment 
Visit 
Day 
(Time Window) 
Screening a 
(Pre-First 
Dose) 
GD\V 
Cycle 1 
Cycles 
2–26 
(± 3 days) 
Cycle 27 – EOT (± 3 days) 
EOT 
Visit 
(±7 days) 
30-Day
Post-EOT 
Safety 
Follow-Up 
(±14 days) 
LTFU 
Every 
3 ± 1 mo d 
Day 1 b 
(Pre-
Dose) 
Day 8 
(± 3 
days) 
Day 15 
(± 3 
days) 
Day 22 
(± 3 
days) 
On Drug 
Therapy c 
Drug 
Holiday 
Pregnancy test by serum or urine 
(only for women of childbearing 
potential)  
X 
X n 
X k 
X 
X 
X 
X 
Thyroid function test (TSH, T3, and 
T4) 
X 
X n 
C2D1, 
C3D1, and 
every other 
cycle 
(C5D1, 
C7D1, etc.) 
X 
X 
X 
Tumor assessment: 
MRI of brain/spine, as appropriate 
X 
X p 
X d 
PK blood samples q 
X  
X 
C2D1, 
C4D1, and 
every 
subsequent 
third cycle 
through 
C13 
(C7D1, 
C10D1, and 
C13D1) 
Karnofsky/Lansky Performance Score 
X 
X 
X 
X k 
X 
X 
X 

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Assessment 
Pre-
Enrollment 
Post-Enrollment 
Visit 
Day 
(Time Window) 
Screening a 
(Pre-First 
Dose) 
GD\V 
Cycle 1 
Cycles 
2–26 
(± 3 days) 
Cycle 27 – EOT (± 3 days) 
EOT 
Visit 
(±7 days) 
30-Day
Post-EOT 
Safety 
Follow-Up 
(±14 days) 
LTFU 
Every 
3 ± 1 mo d 
Day 1 b 
(Pre-
Dose) 
Day 8 
(± 3 
days) 
Day 15 
(± 3 
days) 
Day 22 
(± 3 
days) 
On Drug 
Therapy c 
Drug 
Holiday 
PedsQL-Core, PedsQL-Cancer and 
PROMIS® r 
X 
C4D1 and 
every third 
cycle 
(C7D1, 
C10D1, 
etc.) 
X 
X 
Vineland motor scale s 
X 
C13D1 and 
C26D1 
C39D1 
X 
Telephone follow-up 
X 
X 
Concomitant medication t 
X 
Adverse events 
X u 
Optional tissue collection v 
X 
DAY101 dosing w 
X 
DAY101 administration diary x 
X 
X 
DAY101 drug dispensation/return y 
X 
X 
Post-treatment anti-cancer 
medications 
X 
Survival status 
X 
Abbreviations: AE, adverse event; C, Cycle; D, Day; DOR, duration of response; ECG, electrocardiogram; ECHO, echocardiogram; eCRF, electronic case report form; EOT, end 
of treatment; FFPE, formalin-fixed paraffin embedded; ICF, informed consent form; LTFU, long-term follow-up; MRI, magnetic resonance imaging; MUGA, multiple-gated 
acquisition; OPG; optic pathway glioma; PedsQL-Cancer, Pediatric Quality of Life™—Cancer ; PedsQL-Core, Pediatric Quality of Life Inventory™—Core; PK, 
pharmacokinetics; PROMIS®, Patient-Reported Outcomes Measurement Information System; SAE, serious adverse event; T3, triiodothyronine; T4, tetraiodothyronine; TSH, 
thyroid stimulating hormone. 

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a Results of screening assessments must be reviewed and approved before patient enrollment to confirm that the patient meets the eligibility criteria. 
b Screening tests that are completed within the 48 hours prior to start of DAY101 and duplicate C1D1 tests will be accepted as fulfilling the C1D1 assessments. Repeat testing on 
C1D1 is not necessary for this scenario, and results should be recorded in the screening set of eCRFs. 
c All assessments should be completed at C27D1 and D1 of every third cycle (e.g., C27D1, C30D1, C33D1, etc.) until the EOT visit. 
d Only patients who discontinue treatment due to a reason other than disease progression will continue radiographic tumor assessments. Survival status and subsequent anticancer 
therapies will be collected for patients in LTFU; these data may be obtained by phone. 
e Informed consent/assent may be obtained more than 28 days prior to patient enrollment, but must be provided before any study-specific procedures are performed; however, 
evaluations performed as part of routine care prior to informed consent can be used as screening evaluations if permitted by site Institutional Review Board/Ethics Committee 
policies and performed within protocol-specified windows. 
f Tumor tissue (archival) will be obtained at enrollment whenever available. FFPE tumor blocks are preferred but in cases in which this is not possible, freshly cut FFPE slides 
should be obtained. See the Laboratory Manual for specific instructions. Fresh tissue biopsy is required during screening ONLY if archival tumor tissue sample is not available. 
g All participants will have a neurological, physical, and dermatological examination during screening. For all subsequent visits, the examination will be symptom directed (at 
C1D1 examination should be completed before the first dose of study treatment). 
h Screening ophthalmology examination is required for all patients. For OPG patients or those with an underlying visual deficit related to the primary malignancy, assessment 
completed every time tumor assessments are done and at the EOT visit. The 30-day post-EOT safety follow up visit is required only if following for ocular toxicity. For all other 
patients, symptom-directed examinations may be completed as needed. 
i Screening visual acuity testing is required for all patients. For OPG patients or those with an underlying visual deficit related to the primary malignancy, assessment completed 
every time tumor assessments are done and at the EOT visit. The 30-day post-EOT safety follow up visit is required only if following for ocular toxicity. For all other patients, 
symptom-directed examinations may be completed as needed. 
j For patients > 8 years of age, pubertal stage will be measured before the start of treatment (screening) and yearly thereafter while on active treatment and during LTFU through 
sexual maturity. 
k Assessment completed at D1 of every cycle. 
l On C1D1, ECGs are to be collected predose and in conjunction with PK draws. When ECGs coincide with PK draw days after C1D1, ECGs should be performed after dosing
but before the PK blood draw. Additional ECGs are to be performed if clinically indicated.
m Must use the same assessment (ECHO or MUGA) at screening throughout the study. 
n This assessment is intended to confirm suitability for treatment after enrollment and prior to first dose on C1D1. If this assessment has been performed during screening within 
48 hours (seven days for pregnancy test) prior to C1D1, this assessment does not need to be performed on C1D1 unless the patient’s clinical status has changed (e.g., onset of 
new symptoms indicative of clinical deterioration). If the assessment is performed on C1D1, the results must be reviewed by the investigator prior to any treatment being 
administered. 
o See Section 6.7 and the Laboratory Manual for more detailed information on laboratory assessments.
p MRI of the brain and spine will be performed at screening in all patients. Assessments will be performed at the end of C3 (i.e., on or up to seven days before C4D1), end of C6
(i.e., on or up to seven days before C7D1), and then at the end of every three cycles thereafter (on or up to seven days before Day 1 of the next cycle). Follow-up images can be 
limited to areas with known disease from baseline images. To ensure image consistency, the same imaging modalities and acquisition protocols used at screening are to be used 
for subsequent tumor assessments. MRIs are to be performed per the protocol-defined schedule regardless of whether study treatment is reduced, held, or discontinued. For 
patients who discontinue study treatment before radiographic progressive disease, every effort should be made to document progressive disease with subsequent imaging. 
Confirmation of progression is not required. 
q See Section 6.8, Table 12 for PK sampling schedule. 
r The PROMIS® questionnaire will only be administered to English-speaking patients enrolled in the U.S., Australia, and U.K. 
s The Vineland-3 Motor Skills questionnaire will only be administered to patients enrolled in the U.S., and only by third-party (trained and centralized) personnel. 
t Document concomitant medication taken from 28 days prior to the planned C1D1 through the end of study participation. Only subsequent anticancer therapy(ies) will be 
recorded at LTFU. 

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u Refer to Section 8.1.1 for information on time period and frequency of collecting AE and SAE information. Note: only targeted SAEs will be collected beyond 30 days after last
study drug dose.
v Participants who sign the optional ICF allowing for collection of tumor sample will have tumor specimen collected in the event a tumor-directed surgery occurs during study 
participation. 
w DAY101 will be administered in clinic on C1D1 and at all PK blood draw visits. DAY101 will be taken once weekly at home otherwise until study treatment is discontinued. 
x The study diary will be completed by the patient, or patient's parent or legal guardian, for every dose of study drug administered starting at C1D1. The Investigator or study 
coordinator should review diary entries for compliance, in particular for any potential missed doses, at every in-clinic or remote visit. 
y DAY101 is to be dispensed to patients at D1 of every cycle and any unused drug should be returned at the start of the following cycle. Study drug from last cycle should be 
returned at EOT visit. DAY101 can be dispensed at D1 of every third cycle starting at C27. 

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Table 17: 
Arm 3 Schedule of Assessments 
Assessment 
Pre-
Enrollment 
Post-Enrollment 
Visit 
Day 
(Time Window) 
Screening a 
(Pre-First 
Dose) 
GD\V 
Cycle 1 
Cycles 
2–26 
(± 3 days) 
Cycle 27 – EOT (± 3 days) 
EOT Visit 
(±7 days) 
30-Day
Post-EOT 
Safety 
Follow-Up 
(±14 days) 
LTFU 
Every 
3 ± 1 mo d 
Day 1 b 
(Pre-
Dose) 
Day 8 
(± 3 
days) 
Day 15 
(± 3 
days) 
Day 22 
(± 3 
days) 
On Drug 
Therapy c 
Drug 
Holiday 
Informed consent/assent 
X e 
Demographics, medical, surgical, 
and cancer history (including prior 
12 months of scans, date of 
progression, best response, and 
DOR from prior therapies, and 
tolerability of prior therapy, if 
available) 
X 
Confirmation that archival tumor 
tissue sample is available f 
X 
Physical examination g 
X 
X 
X 
X 
X 
X 
X 
Neurological examination g 
X 
X 
X 
X 
X 
X 
X 
Dermatologic examination incl. 
suspicious lesions g 
X 
X 
X 
X 
X 
X 
X 
Ophthalmology examination h 
X 
Perform every time tumor assessments are done 
X 
X 
Visual acuity testing i 
X 
Perform every time tumor assessments are done 
X 
X 
Tanner Stages j 
X 
C13D1 and 
C27D1 
Once yearly 
Once 
yearly 
Vital signs incl. height and weight 
X 
X 
X 
X k 
X 
X 
X 

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Assessment 
Pre-
Enrollment 
Post-Enrollment 
Visit 
Day 
(Time Window) 
Screening a 
(Pre-First 
Dose) 
GD\V 
Cycle 1 
Cycles 
2–26 
(± 3 days) 
Cycle 27 – EOT (± 3 days) 
EOT Visit 
(±7 days) 
30-Day
Post-EOT 
Safety 
Follow-Up 
(±14 days) 
LTFU 
Every 
3 ± 1 mo d 
Day 1 b 
(Pre-
Dose) 
Day 8 
(± 3 
days) 
Day 15 
(± 3 
days) 
Day 22 
(± 3 
days) 
On Drug 
Therapy c 
Drug 
Holiday 
12-lead ECG in triplicate  l 
X 
X 
predose 
and with 
PK blood 
draws 
X 
C2D1, 
C4D1, and 
every 3rd 
cycle 
through 
C13 
(C7D1, 
C10D1, and 
C13D1) 
X 
Echocardiogram/MUGA m 
X 
C2D1, 
C4D1, and 
every 3rd 
cycle 
(C7D1, 
C10D1, 
etc.) 
X 
X 
Creatine phosphokinase 
X 
C2D1, 
C4D1 and 
every 4th 
cycle 
(C8D1, 
C12D1, 
etc.) 
X 
X 
Hematology and chemistry 
X 
X  n, o 
X 
X k 
X 
X 
X 

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Assessment 
Pre-
Enrollment 
Post-Enrollment 
Visit 
Day 
(Time Window) 
Screening a 
(Pre-First 
Dose) 
GD\V 
Cycle 1 
Cycles 
2–26 
(± 3 days) 
Cycle 27 – EOT (± 3 days) 
EOT Visit 
(±7 days) 
30-Day
Post-EOT 
Safety 
Follow-Up 
(±14 days) 
LTFU 
Every 
3 ± 1 mo d 
Day 1 b 
(Pre-
Dose) 
Day 8 
(± 3 
days) 
Day 15 
(± 3 
days) 
Day 22 
(± 3 
days) 
On Drug 
Therapy c 
Drug 
Holiday 
Pregnancy test by serum or urine 
(only for women of childbearing 
potential)  
X 
X n 
X k 
X 
X 
X 
X 
Thyroid function test (TSH, T3, and 
T4) p 
X 
X n 
C2D1, 
C3D1, and 
every other 
cycle 
(C5D1, 
C7D1, etc.) 
X 
X 
X 
Tumor assessment: CT/MRI/PET 
X 
X q 
X d 
PK blood samples r 
X  
X 
C2D1, 
C4D1, and 
every 
subsequent 
third cycle 
through 
C13 
(C7D1, 
C10D1, and 
C13D1) 
Karnofsky/Lansky Performance 
Score  
X 
X 
X 
X k 
X 
X 
X 

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Assessment 
Pre-
Enrollment 
Post-Enrollment 
Visit 
Day 
(Time Window) 
Screening a 
(Pre-First 
Dose) 
GD\V 
Cycle 1 
Cycles 
2–26 
(± 3 days) 
Cycle 27 – EOT (± 3 days) 
EOT Visit 
(±7 days) 
30-Day
Post-EOT 
Safety 
Follow-Up 
(±14 days) 
LTFU 
Every 
3 ± 1 mo d 
Day 1 b 
(Pre-
Dose) 
Day 8 
(± 3 
days) 
Day 15 
(± 3 
days) 
Day 22 
(± 3 
days) 
On Drug 
Therapy c 
Drug 
Holiday 
PedsQL-Core, PedsQL-Cancer, and 
PROMIS® s 
X 
C4D1 and 
every third 
cycle 
(C7D1, 
C10D1, 
etc.) 
X 
X 
Telephone follow-up 
X 
X 
Concomitant medication t 
X 
Adverse events 
X u 
Optional tissue collection v 
X 
DAY101 dosing w 
X 
DAY101 administration diary x 
X 
X 
DAY101 drug dispensation/return y 
X 
X 
Post-treatment anticancer 
medications 
X 
Survival status 
X 
Abbreviations: AE, adverse event; C, Cycle; D, Day; DOR, duration of response; ECG, electrocardiogram; ECHO, echocardiogram; eCRF, electronic case report form; EOT, end 
of treatment; FFPE, formalin-fixed paraffin embedded; ICF, informed consent form; LTFU, long-term follow-up; MRI, magnetic resonance imaging; MUGA, multiple-gated 
acquisition; OPG; optic pathway glioma; PedsQL-Cancer, Pediatric Quality of Life™—Cancer; PedsQL-Core, Pediatric Quality of Life Inventory™—Core; PK, 
pharmacokinetics; PROMIS®, Patient-Reported Outcomes Measurement Information System; SAE, serious adverse event; T3, triiodothyronine; T4, tetraiodothyronine; TSH, 
thyroid stimulating hormone. 
a Results of screening assessments must be reviewed and approved before patient enrollment to confirm that the patient meets the eligibility criteria. 
b Screening tests that are completed within the 48 hours prior to start of DAY101 and duplicate C1D1 tests will be accepted as fulfilling the C1D1 assessments. Repeat testing on 
C1D1 is not necessary for this scenario, and results should be recorded in the screening set of eCRFs. 

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c All assessments should be completed at C27D1 and D1 of every third cycle (e.g., C27D1, C30D1, C33D1, etc.) until the EOT visit. 
d Only patients who discontinue treatment due to a reason other than disease progression will continue radiographic tumor assessments. Survival status and subsequent anticancer 
therapies will be collected for patients in LTFU; these data may be obtained by phone. 
e Informed consent may be obtained more than 28 days prior to patient enrollment but must be provided before any study-specific procedures are performed; however, evaluations 
performed as part of routine care prior to informed consent can be used as screening evaluations if permitted by site Institutional Review Board/Ethics Committee policies and 
performed within protocol-specified windows. 
f Tumor tissue (archival) will be obtained at enrollment whenever available. FFPE tumor blocks are preferred but in cases in which this is not possible, freshly cut FFPE slides 
should be obtained. See the Laboratory Manual for specific instructions. Fresh tissue biopsy is required during screening ONLY if archival tumor tissue sample is not available. 
g All participants will have a neurological, physical, and dermatological examination during screening. For all subsequent visits, the examination will be symptom directed (at 
C1D1 examination should be completed before the first dose of study treatment). 
h Screening ophthalmology examination is required for all patients. For patients with an underlying visual deficit related to the primary malignancy, assessment completed every 
time tumor assessments are done and at the EOT visit. The 30-day post-EOT safety follow up visit is required only if following for ocular toxicity. For all other patients, 
symptom-directed examinations may be completed as needed 
i Screening visual acuity testing is required for all patients. For patients with an underlying visual deficit related to the primary malignancy, assessment completed every time 
tumor assessments are done and at the EOT visit. The 30-day post-EOT safety follow up visit is required only if following for ocular toxicity. For all other patients, 
symptom-directed examinations may be completed as needed. 
j For patients > 8 years of age, pubertal stage will be measured before the start of treatment (screening) and yearly thereafter while on active treatment and during LTFU through 
sexual maturity. 
k Assessment completed at D1 of every cycle. 
l On C1D1, ECGs are to be collected predose and in conjunction with PK draws. When ECGs coincide with PK draw days after C1D1, ECGs should be performed after dosing
but before the PK blood draw. Additional ECGs are to be performed if clinically indicated.
m Must use the same assessment (ECHO or MUGA) at screening throughout the study. 
n This assessment is intended to confirm suitability for treatment after enrollment and prior to first dose on C1D1. If this assessment has been performed during screening within 
48 hours (seven days for pregnancy test) prior to C1D1, this assessment does not need to be performed on C1D1 unless the patient’s clinical status has changed (e.g., onset of 
new symptoms indicative of clinical deterioration). If the assessment is performed on C1D1, the results must be reviewed by the investigator prior to any treatment being 
administered. 
o See Section 6.7 and the Laboratory Manual for more detailed information on laboratory assessments.
p If clinically indicated (e.g. patients with thyroid cancer).
q Assessments will be performed at the end of C2 (i.e., on or up to seven days before C3D1), end of C4 (i.e., on or up to seven days before C5D1), and then at the end of every
two cycles (on or up to seven days before Day 1 of the next cycle) through 12 months of treatment. Thereafter, patients will undergo radiographic evaluation at the end of every 
three cycles (on or up to seven days before Day 1 of the next cycle). Follow-up images can be limited to areas with known disease from baseline images. To ensure image 
consistency, the same imaging modalities and acquisition protocols used at screening are to be used for subsequent tumor assessments. Imaging is to be performed per the 
protocol-defined schedule regardless of whether study treatment is reduced, held, or discontinued. For patients who discontinue study treatment before radiographic progressive 
disease, every effort should be made to document progressive disease with subsequent imaging. Confirmation of progression is not required. 
r See Section 6.8, Table 12 for PK sampling schedule. 
s The PROMIS® questionnaire will only be administered to English-speaking patients enrolled in the U.S., Australia, and U.K. 
t Document concomitant medication taken from 28 days prior to the planned C1D1 through the end of study participation. Only subsequent anticancer therapy(ies) will be 
recorded at LTFU. 
u Refer to Section 8.1.1 for information on time period and frequency of collecting AE and SAE information. Note: only targeted SAEs will be collected beyond 30 days after last
study drug dose.

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v Participants who sign the optional ICF allowing for collection of tumor sample will have tumor specimen collected in the event a tumor-directed surgery occurs during study 
participation. 
w DAY101 will be administered in clinic on C1D1 and at all PK blood draw visits. DAY101 will be taken once weekly at home otherwise until study treatment is discontinued. 
x The study diary will be completed by the patient, or patient's parent or legal guardian, for every dose of study drug administered starting at C1D1. The Investigator or study 
coordinator should review diary entries for compliance, in particular for any potential missed doses, at every in-clinic or remote visit. 
y DAY101 is to be dispensed to patients at D1 of every cycle, and any unused drug should be returned at the start of the following cycle. Study drug from last cycle should be 
returned at EOT visit. DAY101 can be dispensed at D1 of every third cycle starting at C27. 

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Appendix B: 
Karnofsky and Lansky Performance Status Scales 
Table 18: 
Karnofsky Performance Score ( 16 years old) 
Score 
Karnofsky Description 
100 
Normal; no complaints; no evidence of disease 
90 
Able to carry on normal activity; minor signs or symptoms of disease 
80 
Normal activity with effort; some signs or symptoms of disease 
70 
Cares for self; unable to carry on normal activity or do active work 
60 
Requires occasional assistance, but is able to care for most personal needs 
50 
Requires considerable assistance and frequent medical care 
40 
Disabled; requires special care and assistance 
30 
Severely disabled; hospitalization is indicated, although death not imminent 
20 
Very sick; hospitalization necessary; active support treatment is necessary 
10 
Moribund; fatal processes progressing rapidly 
0 
Dead 
(Karnofsky and Burchenal 1949) 
Table 19: 
Lansky Performance Score (< 16 years old) 
Score 
Lansky Description 
100 
Fully active, normal 
90 
Minor restrictions in strenuous physical activity 
80 
Active, but tired more quickly 
70 
Greater restriction of play and less time spent in play activity 
60 
Up and around, but active play minimal; keeps busy by being involved in quieter activities 
50 
Lying around much of the day, but gets dressed; no active playing, participates in all quiet play 
and activities 
40 
Mainly in bed; participates in quiet activities 
30 
Bed bound; needing assistance even for quiet play 
20 
Sleeping often; play entirely limited to very passive activities 
10 
Doesn’t play; doesn’t get out of bed 
0 
Unresponsive 
(Lansky et al. 1987) 

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Appendix D: 
Response Assessment in Neuro-Oncology (RANO) Criteria for 
Primary CNS Malignancies 
The RANO criteria (Wen 2010) were developed to evaluate efficacy of investigational agents 
in glioblastoma clinical trials and have been more broadly used for lower grade primary CNS 
malignancies. These criteria were developed in part to address issues faced when assessing 
some lesions based on MacDonald criteria, particularly lesions with central necrosis and with 
a T2 component. 
Table 22: 
RANO Response Criteria Incorporating MRI and Clinical Factor 
RESPONSE CATEGORY 
CRITERIA 
Complete Response 
x
Disappearance of all measurable and nonmeasurable
enhancing disease
x
Stable or improved nonenhancing FLAIR/T2 lesions
x
No new lesions
x
Clinically stable or improved with no reliance on
corticosteroids (except for physiological replacement)
Partial Response 
x
 50% decrease from baseline of all measurable
enhancing lesions
x
No progression of nonmeasurable disease
x
Stable or improved nonenhancing FLAIR/T2 lesions
x
No new lesions
x
Clinically stable or improved, with stable or reduced
corticosteroids compared to baseline
Progressive Disease 
x
 25% increase from baseline in enhancing lesions
despite stable or increasing steroid dose
x
Significant increase in nonenhancing FLAIR/T2 lesions
not attributable to other nontumor causes
x
Any new lesions
x
Clinical deterioration no attributable to other nontumor
causes and not due to steroid decrease
Stable Disease 
x
Does not meet other criteria for response or progression
x
Stable nonenhancing FLAIR/T2 lesions
x
Clinically stable with stable or reduced corticosteroids
compared to baseline
Abbreviations: FLAIR/T2, T2-weighted fluid-attenuated inversion recovery; MRI, magnetic resonance 
imaging; RANO, Response Assessment in Neuro-Oncology. 
A measurable lesion is evaluated by contrast-enhancing MRI and: 
x
Has clearly defined margins
x
Is visible on 2 or more axial slices, preferably < 5 mm thick
x
Is at least 10 mm in size if slice thickness is < 5 mm (or 2× slice thickness if
> 5 mm)
x
Does not measure a cystic cavity

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Non-measurable lesions are those that do not fit the criteria above, and specifically lesions 
that are cystic, necrotic, or include a surgical cavity should not be considered measurable. 
Measurements are calculated by summing the products of perpendicular diameters of all 
measurable enhancing lesions. 
If there are multiple contrast-enhancing lesions, a minimum of the two largest lesions should 
be measured. However, emphasis should be placed on selecting lesions that allow 
reproducible repeated measurements. For patients who have multiple lesions for which only 
one or two are increasing in size, the enlarging lesions should be considered the measurable 
lesions for evaluation of response. 

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Appendix E: 
Response Evaluation Criteria in Solid Tumors: Revised RECIST 
Guideline (version 1.1) 
A revised RECIST guideline (version 1.1) was developed by the RECIST Working Group 
(Eisenhauer et al. 2009). Notable changes are highlighted below: 
x
Number of lesions required to assess tumor burden for response determination has
been reduced from a maximum of 10 to a maximum of five total (and from five to
two per organ, maximum).
x
Nodes with a short axis of 15 mm are considered measurable and assessable as
target lesions. Nodes that shrink to < 10 mm short axis are considered normal.
x
In addition to the previous definition of progression in target disease of 20%
increase in sum, a 5-mm absolute increase is now required as well.
Measurability of Tumor Lesions at Baseline 
Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in 
the plane of measurement is to be recorded) with a minimum size of: 
x
10 mm by CT scan (CT scan slice thickness no greater than 5 mm) and 20 mm by
chest X-ray
x
10-mm caliper measurement by clinical exam (lesions which cannot be accurately
measured with calipers should be recorded as non-measurable).
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph 
node must be t 15 mm in short axis when assessed by CT scan (CT scan slice thickness 
recommended to be no greater than 5 mm). At baseline and in follow-up, only the short axis 
will be measured and followed. 
Special considerations regarding lesion measurability of bone lesions, cystic lesions, and 
lesions previously treated with local therapy can be found in RECIST version 1.1 and are 
briefly summarized as follows: 
x
Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue
components, that can be evaluated by cross sectional imaging techniques such as
CT or MRI can be considered as measurable lesions if the soft tissue component
meets the definition of measurability described above.
x
“Cystic lesions” thought to represent cystic metastases can be considered as
measurable lesions if they meet the definition of measurability described above.
x
Tumor lesions situated in a previously irradiated area, or in an area subjected to
other loco-regional therapy, are usually not considered measurable unless there
has been demonstrated progression in the lesion.
Specifications by Methods of Measurements 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging based evaluation 

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should always be done rather than clinical examination unless the lesion(s) being followed 
cannot be imaged but are assessable by clinical exam. 
Clinical lesions: Clinical lesions will only be considered measurable when they are 
superficial and t10mm diameter as assessed using calipers (e.g. skin nodules). For the case 
of skin lesions, documentation by color photography including a ruler to estimate the size of 
the lesion is suggested. 
Chest X-ray: Chest CT is preferred over chest X-ray, particularly when progression is an 
important endpoint, since CT is more sensitive than X-ray, particularly in identifying new 
lesions. However, lesions on chest X-ray may be considered measurable if they are clearly 
defined and surrounded by aerated lung. 
CT, MRI: CT is the best currently available and reproducible method to measure lesions 
selected for response assessment. This guideline has defined measurability of lesions on CT 
scan based on the assumption that CT slice thickness is d 5mm. 
MRI is also acceptable in certain situations (e.g. for body scans). 
Use of ultrasound, endoscopy, laparoscopy, biomarker, and cytology/histology are not 
recommended for additional details refer to RECIST v1.1. 
Tumor Response Evaluation 
To assess objective response or future progression, it is necessary to estimate the overall 
tumor burden at baseline and use this as a comparator for subsequent measurements. 
Measurable disease is defined by the presence of at least one measurable lesion. 
A maximum of five lesions total (and a maximum of two lesions per organ) representative of 
all involved organs should be identified as target lesions and will be recorded and measured 
at baseline. A sum of the diameters (longest for non-nodal lesions, short axis for nodal 
lesions) for all target lesions will be calculated and reported as the baseline sum diameters. 
All other lesions (or sites of disease) including pathological lymph nodes should be identified 
as non-target lesions and should also be recorded at baseline. Measurements are not required 
and these lesions should be followed as “present,” “absent,” or in rare cases “unequivocal 
progression.” 
Evaluation of Target Lesions 
x
Complete Response (CR): Disappearance of all target lesions. Any pathological
lymph nodes (whether target or non-target) must have reduction in short axis to
< 10 mm.
x
PR: At least a 30% decrease in the sum of diameters of target lesions, taking as
reference the baseline sum diameters.

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x
Progressive Disease (PD): At least a 20% increase in the sum of diameters of
target lesions, taking as reference the smallest sum on study (this includes the
baseline sum if that is the smallest on study). In addition to the relative increase of
20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note:
the appearance of one or more new lesions is also considered progression).
x
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient
increase to qualify for PD, taking as reference the smallest sum diameters while
on study.
Evaluation of Non-Target Lesions 
While some non-target lesions may actually be measurable, they need not be measured and 
instead should be assessed only qualitatively at the time points specified in the protocol. 
x
Complete Response (CR): Disappearance of all non-target lesions and
normalization of tumor marker level. All lymph nodes must be non-pathological
in size (<10 mm short axis).
x
Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or
maintenance of tumor marker level above the normal limits.
x
Progressive Disease (PD): Unequivocal progression (see comments below) of
existing non-target lesions. (Note: the appearance of one or more new lesions is
also considered progression).
Evaluation of Best Overall Response 
The BOR is determined once all the data for the patient is known. Guidance on the 
determination of tumor response at each time point is provided in Table 23. Complete or 
partial responses may be claimed only if the criteria for each are met at a subsequent time 
point as specified in the protocol (generally four weeks later). Guidance on the determination 
of best overall confirmed response is provided in Table 24. 
Patients with a global deterioration of health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be classified as having 
symptomatic deterioration. Every effort should be made to document objective disease 
progression, even after discontinuation of treatment. 
In some circumstances, it may be difficult to distinguish residual disease from normal tissue. 
When the evaluation of CR depends on this determination, it is recommended that the 
residual lesion be investigated, i.e., biopsied if accessible. 

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Table 23: 
Overall Assessment by RECIST v1.1 at Each Time Point 
Abbreviations: BL, baseline; CR, complete response; NE, not all evaluated; PD, progressive disease; PR, partial 
response; SD, stable disease. 
Target Lesion 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
CR or none at BL 
No 
CR 
CR 
Non-CR/Non-PD 
No 
PR 
CR 
Not all evaluated (NE) 
No 
PR 
PR 
Non-PD or not all 
evaluated or none at BL 
No 
PR 
SD 
Non-PD or not all 
evaluated or none at BL 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
None identified at BL 
CR 
No 
CR 
None identified at BL 
Non-CR/Non-PD 
No 
Non-CR/Non-PD 
None identified at BL 
Not all evaluated 
No 
NE 
None identified at BL 
PD 
Yes or No 
PD 
None identified at BL 
None identified at BL 
Yes 
PD 

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Table 24: 
Best Overall Assessment by RECIST v1.1 
Abbreviations: CR, complete response; NE, not all evaluated; PD, progressive disease; PR, partial response; 
SD, stable disease. 
a If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting 
PR criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after 
CR). Best response would depend on whether minimum duration for SD was met. However, sometimes ‘CR’ 
may be claimed when subsequent scans suggest small lesions were likely still present and in fact the patient had 
PR, not CR at the first time point. Under these circumstances, the original CR should be changed to PR and the 
best response is PR. 
Overall Response 
First Time Point 
Overall Response 
Subsequent Time Point 
Best Confirmed Overall Response 
CR 
CR 
CR 
CR 
PR 
PRa, SD, PD 
CR 
SD 
SD provided minimum criteria for SD duration 
met, otherwise, PD 
CR 
PD 
SD provided minimum criteria for SD duration 
met, otherwise, PD 
CR 
NE 
SD provided minimum criteria for SD duration 
met, otherwise, NE 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 
PR 
PD 
SD provided minimum criteria for SD duration 
met, otherwise, PD 
PR 
NE 
SD provided minimum criteria for SD duration 
met, otherwise, NE 
NE 
NE 
NE 

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Appendix F: 
Specimen and Data Use 
Research Uses of Tissue and Clinical Data 
Any leftover tissue samples will be banked for future analyses that are not yet available. 
Clinical data and tissue samples, independently and together, will be used for nontherapeutic 
research that advances the diagnosis, evaluation, etiology, prevention, and outcome 
improvement of nervous system diseases. Research on tissue samples may include detailed 
genomic and molecular analysis. In general, these findings will be linked to clinical care and 
outcome to maximize research findings. Studies may include tumor biology studies, 
biomarker identification studies, drug target studies, genomics and proteomics studies, 
genetic susceptibility studies, drug development efforts, epidemiological studies, and 
outcomes studies. Use of leftover tissue samples is optional and can only be done with the 
consent of the patient. 
Retrospective analysis on clinical data performed outside of prospective formal clinical trial 
data will be linked with outcomes to create research findings and provide preliminary data to 
support further investigations. 
Commercial Uses of Tissue and Clinical Data 
Tissue samples collected and/or stored in the bank may be made available to commercial or 
corporate scientific collaborators only as part of a scientific collaboration. Derivative 
products from the patient tissues, including diagnostics tests or other items, may arise from 
study of these tissues. Patients will not have any ownership or financial benefit from their 
tissue samples and derivatives. 
Uses That May Affect Determination of Treatment (Clinical Care) and/or Eligibility in 
Clinical Trials 
In rare circumstances, findings from tissue testing may be clinically relevant and affect 
treatment decisions. All testing results communicated back to the patient’s treating clinician 
and/or placed into the patient’s medical record must be CLIA compliant. If the testing is first 
done in a laboratory that does not meet these criteria, yet the results are felt to be clinically 
significant, the testing will be repeated in a CLIA environment prior to informing the 
patient’s clinician and/or placement in the patient’s medical record. The patient’s treating 
clinician is responsible for treatment decisions including whether and how to inform the 
patient of any results. 

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Appendix G: 
Blood Pressure by Height and Age 
The tables for normal blood pressure (BP) by height and age are included in this appendix. In 
order to use these tables, note that the height percentile is determined by the standard growth 
charts. The child’s measured systolic and diastolic BP is compared with the numbers 
provided in the table (boys or girls) for age and height percentile. 
x
The child is normotensive if BP is below the 90th percentile.
x
If the child’s BP (systolic or diastolic) is at or above the 95th percentile, the child
may be hypertensive, and repeated measurements are indicated.
x
BP measurements between the 90th and 95th percentiles are high normal and
warrant further observation and consideration of other risk factors.
Standards for systolic and diastolic BP for infants younger than 1 year are available in the 
second task force report. Recently, additional data have been published. In children younger 
than 1 year, systolic BP has been used to define hypertension. 
Source: DHHS, PHS, NIH, National Heart, Lung, and Blood Institute. Update on the Task 
Force Report (1987) on High Blood Pressure in Children and Adolescents: A Working Group 
Report from the National High Blood Pressure Education Program. NIH Publication 
96-3790; 1996; 7-9.
The entire NIH document can be viewed at: 
http://www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_ped.pdf. 

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DOT Therapeutics-1 Inc. (Day One) 
Clinical Protocol DAY101-001 
DAY101 
21 Oct 2021 
Version 3.0 Final 
Confidential & Proprietary 
Page 129 of 138 
Appendix I: 
Visual Acuity Testing 
Visual acuity testing using the appropriate age-specific testing methodology will be 
performed for all patients at screening. For patients with OPG or an underlying visual deficit 
related to the primary malignancy, visual acuity testing will be performed every time patients 
have a radiographic disease assessment. A forced choice preferential looking test is preferred. 
Testing may be done by an ophthalmologist or other qualified site clinical personnel. To 
reduce variability in scoring, the same BCVA testing methodology should be used 
throughout the treatment period. Best corrected visual acuity will be reported in logMAR. 
Reasons for BCVA testing not being completed will be recorded. 
Visual Acuity in Feet and logMAR Equivalents for Acuity in Cycles/cm 
TAC II @ 55 cm (Cycles/cm) 
VA equivalent 
logMAR 
26 
20/24 
0.06 
19 
20/32 
0.20 
13 
20/47 
0.36 
9.8 
20/63 
0.49 
6.5 
20/94 
0.66 
4.8 
20/130 
0.80 
3.2 
20/190 
0.97 
2.4 
20/260 
1.10 
1.6 
20/380 
1.27 
1.3 
20/470 
1.36 
0.86 
20/710 
1.54 
0.64 
20/960 
1.67 
0.43 
20/1400 
1.84 
0.32 
20/1900 
1.97 
Abbreviations: logMAR, logarithm of the minimum angle of resolution; TAC, Teller Acuity Cards®; VA, visual 
acuity. 
HOTV or other ETDRS assessments should be attempted on patients who are old enough, 
based on local standard practice. Assessments will be performed in each eye separately at a 
recommended testing distance of 3 meters (or local standard practice). Best corrected visual 
acuity will be reported in logMAR. 
Reasons for VA testing not being completed will be recorded (e.g., bilateral blindness with 
no light perception). 

DOT Therapeutics-1 Inc. (Day One) 
Clinical Protocol DAY101-001 
DAY101 
21 Oct 2021 
Version 3.0 Final 
Confidential & Proprietary 
Page 130 of 138 
NOTE: A 0.2 logMAR worsening (or up to a two-card drop in Teller acuity) will not be 
considered visual progressive disease at the first on-therapy staging evaluation (at 12 weeks) 
if the tumor is stable or smaller on the MRI. In these cases, a repeat VA assessment will be 
required six weeks later to confirm that further visual progression is not occurring. If the 
repeat VA is stable or improved (0.2 logMAR or less [or a two-card drop in Teller acuity or 
OHVV@IURPSUHWUHDWPHQWEDVHOLQHWKHSDWLHQWZLOOUHPDLQRQSURWRFROWherapy. 
VA Norms 
Note: The rate of visual development varies across patients. The table is presented as a 
reference only. 
Age 
Grating Acuity by TAC II 
Recognition Acuity 
Normal VA 
(cy/cm) 
logMAR 
Snellen 
Equivalent b 
Normal VA 
(feet) 
logMAR 
6 m 
2.4 
1.097 
20/260 
— 
— 
12 m 
3.2 
0.972 
20/190 
— 
— 
18 m 
4.8 
0.796 
20/130 
— 
— 
24 m 
4.8 
0.796 
20/130 
— 
— 
30 m 
6.5 
0.664 
20/94 
— 
— 
36 m 
9.8 
0.486 
20/63 
— 
— 
42 m 
13.0 
0.363 
20/47 
— 
— 
48 m 
— 
— 
— 
20/32 
0.2 
5 y 
— 
— 
— 
20/25 
0.10 
 6 y 
— 
— 
— 
20/20 
0.00 
Abbreviations: CI, confidence interval; logMAR, logarithm of the minimum angle of resolution; TAC, Teller 
Acuity Cards®; VA, visual acuity. 
a 1RUPDO9$ZLWK7$&>ORZOLPLWRIQRUPDODW&,@ 
b Conversion of grating acuity to Snellen equivalents is not recommended and is only provided for purposes of 
communication. 
Visual Fields: 
Visual field testing will be performed unilaterally by confrontation and reported by capturing 
the corresponding quadrant(s) with a deficit (1, 2, 3, or 4) . 
Optic Disc Appearance: 
Optic discs will be assessed unliterally for the presence or absence of pallor and edema. 

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DOT Therapeutics-1 Inc. (Day One) 
Clinical Protocol DAY101-001 
DAY101 
21 Oct 2021 
Version 3.0 Final 
Confidential & Proprietary 
Page 136 of 138 
Appendix K: 
Contraceptive Guidance and Collection of Pregnancy Information 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered to be fertile following menarche and until becoming postmenopausal, 
unless permanently sterile (see below). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should be 
considered. 
Women in the following categories are not considered WOCBPs: 
x
Premenarchal
x
Premenopausal woman with one of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy

For individuals with permanent infertility due to an alternate medical cause
other than the above (e.g., Müllerian agenesis, androgen insensitivity),
investigator discretion should be applied to determining study entry.
Note: Documentation can come from the site personnel’s review of the
patient’s medical records, medical examination, or medical history interview.
Contraception Guidance: 
For male patients with a pregnant partner, a condom should be used for contraception in 
addition to one of the highly effective contraception methods described below. 
For male patients with a nonpregnant female partner of childbearing potential or a female 
patient of childbearing potential, one of the following highly effective birth control methods 
with a failure rate of less than 1% per year must be applied: 
x
Combined estrogen- and progestogen-containing hormonal contraception
associated with inhibition of ovulation given PO, intravaginally, or transdermally
x
Progestin-only hormonal contraception associated with inhibition of ovulation
given PO, by injection, or by implant
x
Intrauterine device (IUD)
x
Intrauterine hormone-releasing system (IUS)
x
Bilateral tubal occlusion or ligation

DOT Therapeutics-1 Inc. (Day One) 
Clinical Protocol DAY101-001 
DAY101 
21 Oct 2021 
Version 3.0 Final 
Confidential & Proprietary 
Page 137 of 138 
x
Vasectomized partner
x
Sexual abstinence
In the context of this protocol, sexual abstinence is considered a highly effective method only 
if defined as refraining from heterosexual intercourse during the entire period specified 
above. Periodic abstinence (calendar, symptothermal, post-ovulation methods) and 
withdrawal (coitus interruptus) are not acceptable methods of contraception. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the subject. 
If a male subject or male partner of a female subject uses a condom during intercourse, they 
must also use one of the methods above. Using a condom by itself is NOT considered a 
highly effective method of contraception. 
Collection of Pregnancy Information 
Male Patients With Partners Who Become Pregnant 
x
The investigator will attempt to collect pregnancy information on any male
patient’s female partner who becomes pregnant while the male patient is in this
study. This applies only to male patients who receive DAY101.
x
After obtaining the necessary signed informed consent from the pregnant female
partner directly, the investigator will record pregnancy information on the
appropriate form and submit it to the Sponsor within 24 hours of learning of the
partner’s pregnancy. The female partner will also be followed to determine the
outcome of the pregnancy. Information on the status of the mother and child will
be forwarded to the Sponsor. Generally, the follow-up will be no longer than six
months following the estimated delivery date. Any termination of the pregnancy
will be reported regardless of fetal status (presence or absence of anomalies) or
indication for the procedure.
Female Patients Who Become Pregnant 
x
The investigator will collect pregnancy information on any female patient who
becomes pregnant while participating in this study. The initial information will be
recorded on the appropriate form and submitted to the Sponsor within 24 hours of
learning of the patient’s pregnancy.
x
The patient will be followed to determine the outcome of the pregnancy. The
investigator will collect follow-up information on the patient and the neonate and
the information will be forwarded to the Sponsor. Generally, follow-up will not be
required for longer than six months beyond the estimated delivery date. Any
termination of pregnancy will be reported, regardless of fetal status (presence or
absence of anomalies) or indication for the procedure.

DOT Therapeutics-1 Inc. (Day One) 
Clinical Protocol DAY101-001 
DAY101 
21 Oct 2021 
Version 3.0 Final 
Confidential & Proprietary 
Page 138 of 138 
x
While pregnancy itself is not considered to be an AE or SAE, any pregnancy
complication or elective termination of a pregnancy for medical reasons will be
reported as an AE or SAE.
x
A spontaneous abortion (occurring at < 22 weeks gestational age) or still birth
(occurring at > 22 weeks gestational age) is always considered to be an SAE and
will be reported as such.
x
Any post-study pregnancy-related SAE considered reasonably related to the study
intervention by the investigator will be reported to the Sponsor as described in
Section 8.1.5. While the investigator is not obligated to actively seek this
information in former study patients, he or she may learn of an SAE through
spontaneous reporting.
x
Any female patient who becomes pregnant while participating in the study will
discontinue study intervention.