A Phase 2, Subprotocol of DAY101 Monotherapy for Patients With Recurrent, Progressive, or Refractory Solid Tumors With MAPK Pathway Aberrations
Phase: PHASE2
Conditions: Melanoma, Solid Tumor, CRAF Gene Amplification, RAF1 Gene Amplification, BRAF Gene Fusion, BRAF Fusion, CRAF Gene Fusion, CRAF Fusion, RAF1 Gene Fusion, RAF1 Fusion, Thyroid Cancer, Papillary, Spitzoid Melanoma, Pilocytic Astrocytoma, Pilocytic Astrocytoma, Adult, Non Small Cell Lung Cancer, Non-Small Cell Adenocarcinoma, Colorectal Cancer, Pancreatic Acinar Carcinoma, Spitzoid Malignant Melanoma, Bladder Cancer, Bladder Urothelial Carcinoma, MAP Kinase Family Gene Mutation, RAF Mutation
Sponsor: Day One Biopharmaceuticals, Inc.

 
CLINICAL MASTER PROTOCOL DAY101-102 
A Phase 1b/2, Open Label Study of DAY101 Monotherapy 
or Combination with Other Therapies for Patients with 
Recurrent, Progressive, or Refractory Solid Tumors 
Harboring MAPK Pathway Aberrations 
Investigational Product: 
DAY101 
Protocol Number: 
DAY101-102 
IND #: 
108340 
EudraCT #: 
2021-003768-29 
Development Phase: 
1b/2 
Sponsor: 
Day One Biopharmaceuticals, Inc. (Day One) 
2000 Sierra Point Parkway, Suite 501 
Brisbane, CA 94005 
Original Protocol 
09 February 2021 
Protocol Amendment 1.0 
Protocol Amendment 2.0 
01 September 2021 
13 October 2022 
 
 
Confidentiality Statement 
This document contains confidential information that is the property of Day One and may not be disclosed to 
anyone other than the recipient clinical Investigator, research staff, and respective members of the Institutional 
Review Board//Research Ethics Board/Independent Ethics Committee/Human Research Ethics Committee. This 
information cannot be used for any purpose other than the evaluation of conduct of the clinical investigation 
without the prior written consent of Day One. 

Day One Biopharmaceuticals, Inc.  (Day One) 
Clinical Protocol DAY101-102 
DAY101 
 
13 October 2022 
Protocol Amendment 2.0 Final 
Confidential & Proprietary 
Page 3 
PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Master Protocol DAY101-102 has been amended to incorporate the following major changes. 
The changes and rationale for each change are summarized in the table below.  
Section(s) 
Description of Change  
Brief Rationale 
Title page 
Updated Sponsor address. 
Administrative. 
Title page, 
Approval page 
Protocol versions will be referred to as 
protocol amendments. 
Revised to align with company formatting. 
List of 
Abbreviations and 
Definition of 
Terms 
Revised list of abbreviations. 
Align with current version of protocol 
Synopsis, 2 
Revised Phase 1b/2 exploratory 
objective.  
Revised to reflect genomic alterations in 
circulating tumor DNA (ctDNA) will be 
characterized. 
Synopsis, 4.1, 4.2 
Moved all eligibility criteria into 
sub-protocols. 
Restructured eligibility criteria between 
DAY101-102 and sub-protocols. 
1.2.1 
Revised languages on metabolic 
pathway and conclusions for drug-drug 
interaction potentials.   
Provided clarity on DAY101 drug-drug 
interaction potentials with concomitant 
drugs. 
1.2.2, 1.3.2 
Added description for Study 
 Study
and 
FIREFLY-1/PNOC026.  
Provided a concise summary of safety data 
for Study
and data on the PK 
profile of DAY101 tablet and powder for 
reconstitution (PfR) formulations for Study 
1.2.2.2, 1.2.2.3 
Added clinical efficacy and safety data 
from Study FIREFLY-1/PNOC026. A 
table of TEAEs was added from 
completed Study C28001. Revised data 
from Study
To add findings as of the data cutoff of 14 
April 2022 and to provide additional 
background on the safety data. 
1.3.1 
Removed mention of Harvey Rat 
Sarcoma Virus (HRAS) mutation.  
HRAS mutation is not mentioned in 
referenced sub-protocol. 
1.3.2 
Updated the justification for dose. 
Revised data from Study 
 
Provided a concise summary of data on 
the pharmacokinetic (PK) profile of 
DAY101 tablet formulation. 
Revised data from Study
Revised results from Study 
. 
Provided a concise summary of data on the 
PK profile of DAY101 tablet and PfR 
formulations. 
1.3.3 
Updated section and guidance regarding 
CYP2C8 inhibitors or inducers. 
Based on updated available information. 
1.3.4 
Updated Benefit/Risk description. 
Updated based on updated available clinical 
data. 

Day One Biopharmaceuticals, Inc.  (Day One) 
Clinical Protocol DAY101-102 
DAY101 
 
13 October 2022 
Protocol Amendment 2.0 Final 
Confidential & Proprietary 
Page 4 
Section(s) 
Description of Change  
Brief Rationale 
2 (Table 2) 
Removed duplicate secondary objective. 
Revised per protocol clarification 
letter-Canada recommendations. ORR is 
erroneously listed as a secondary endpoint 
whereas it serves as a primary endpoint 
only for the Phase 2 portion of the study. 
3.1 
Added “and combination partner if 
applicable” with regards to continuing 
with drug if patient has radiographic 
evidence of disease progression. 
Revised for consistency with sub-protocol 
DAY101-102b. 
3.1 
Revised schema. 
Removed indication expansion and updated 
schema for clarity. 
3.1 
Removed body surface area (BSA) 
parameter for patients ages 12 up to <18 
years.  
BSA ≥ 1.5 m2 for patients 12 up to < 18 
years is not an eligibility criterion. 
5.1 
Removed dispensing instructions.  
Details to be provided in the Pharmacy 
Manual. 
5.2.1 
Clarified dosing instructions. 
General dosing instructions revised to align 
with DAY101 programs. 
5.2.3, 5.2.4 
Removed dose modification and 
management of treatment-related event 
details. 
Details can be found in respective sub-
protocols. 
5.4.4 
Clarified window for recording 
medications in electronic case report 
form. 
Revised to align between studies. 
5.4.5 
Removed palliative radiotherapy details. 
Relocated details to respective sub-
protocols. 
5.5 
Added preparation, handling, storage, 
and accountability for study drug. 
To provide guidance and clarify medication 
handling. 
6.2 
Removed statement that patients that are 
lost to follow up will be replaced. 
Updated enrollment procedure 
6.4 
Removed archival and tumor sample 
details. 
Relocated details to respective sub-
protocols. 
6.5 
Added section for fresh tumor samples 
for pharmacodynamic analysis.  
Clarity to site and investigator. 
6.7 
Added section for ctDNA blood sample 
collection. 
Clarity to site and investigator. 
6.9 
Added Tanner Staging for assessment of 
pubertal development. 
Clarity to site and investigator. 
6.9, Appendix H 
Removed routes of obtaining body 
temperature.  
Addition of oxygen saturation 
assessment to vital signs  
Per French National Agency for the Safety 
of Medicines and Health Products (ANSM) 
request, added oxygen saturation for 
monitoring of pulmonary toxicities. 
6.10 
Clarified blood pressure assessment in 
pediatric patients. 
Clarity to site and investigator. 

Day One Biopharmaceuticals, Inc.  (Day One) 
Clinical Protocol DAY101-102 
DAY101 
 
13 October 2022 
Protocol Amendment 2.0 Final 
Confidential & Proprietary 
Page 5 
Section(s) 
Description of Change  
Brief Rationale 
6.13 
Added recommendation for prophylactic 
skin care regimen and management 
options. 
Clarity to site and investigator. 
6.15 
Added bone age and height assessment. 
For additional collection of data.  
6.17 
Added guidance regarding laboratory 
tests for patients ages 12 up to <18 
years. 
Clarity to site and investigator. 
6.17.2 
Removed neutrophil (count and 
percentage) and lymphocytes. 
Removed the specification since already 
included with current assessment. 
6.17.3 
Addition of the following chemistry 
assessments: serum calcium (corrected 
calcium), creatinine clearance, 
phosphate, and magnesium. 
Per Agence Nationale de Sécurité du 
Médicament et des Produits de Santé 
(ANSM) request, additional assessments 
added to monitoring parameters. 
6.17.5 
Clarified triiodothyronine (T3) testing. 
To clarify T3 may be obtained as a 
reflexive test if considered necessary by the 
Investigator based on local practice. 
6.19.1 
Added that CT/MRI must be performed 
within 28 days prior to first dose of 
study drug. 
Clarity to site and investigator. 
6.20 
Removed 7-day monitoring period. 
Details specified in sub-protocols. 
6.25 
Removed timeframes for AE reporting. 
To reduce discrepancies. 
7 
Removed details. 
Details can be found in sub-protocols and 
SAP. 
7.1 
Revised analysis population. 
To clarify efficacy population. 
7.3.1 
Revised efficacy analyses. 
To align with efficacy population 
description.  
7.3.2 
Revised safety analyses. 
To clarify how information will be 
tabulated and included in summary tables 
and listings for all reported TEAEs. 
7.3.2.2 
Added descriptive statistic language. 
To clarify descriptive statistics used for 
clinical laboratory parameters. 
8, Appendix G 
Added adverse events of special interest 
guidance.  
To clarify that safety monitoring 
includes all AESIs. 
8.1.4 
Updated regulatory reporting 
requirements to clarify SAE and AESI 
reporting. 
Clarity to site and investigator. 
8.1.5 
Clarified reporting is for DAY101 or 
combination partner, whichever 
administered last. 
To clarify reporting window. 
8.2; 8.2.1; 8.2.2 
Revised language to reflect Safety 
Review Committee and Independent 
Monitoring Committee (IDMC) will be 
established. 
Per Federal Agency for Medicines and 
Health Products (FAMHP) request, added 
the implementation of an IDMC for 
analysis of cumulative safety data 
throughout study conduct. 

Day One Biopharmaceuticals, Inc.  (Day One) 
Clinical Protocol DAY101-102 
DAY101 
 
13 October 2022 
Protocol Amendment 2.0 Final 
Confidential & Proprietary 
Page 6 
Section(s) 
Description of Change  
Brief Rationale 
9.2 
Removed eCRF window. 
To reduce redundancy. Information is in the 
electronic data capture manual. 
10 
Added new citations. 
Updated to reflect current version of 
protocol. 
Appendix F 
Revised contraceptive guidance. 
Contraceptive guidance information has 
been revised to align with DAY101 
programs. 
Additional minor formatting and editorial changes (not listed in the table above) have been 
made to improve clarity and to correct grammar and typographical errors. These include 
revisions to abbreviations and literature references, as applicable. 

Day One Biopharmaceuticals, Inc.  (Day One) 
Clinical Protocol DAY101-102 
DAY101 
 
13 October 2022 
Protocol Amendment 2.0 Final 
Confidential & Proprietary 
Page 7 
SYNOPSIS 
TITLE: 
A Phase 1b/2, Open Label Study of DAY101 Monotherapy or Combination with Other Therapies for Patients 
with Recurrent, Progressive, or Refractory Solid Tumors Harboring MAPK Pathway Aberrations. 
STUDY SITES: 
See sub-protocol for details.  
PHASE: 
1b/2 
OBJECTIVES: 
The Phase 1b objectives will only apply to sub-protocol of DAY101 in combination with other therapies. 
Phase 1b 
The Phase 1b objectives will apply to the investigation of DAY101 in combination with other therapies. 
Additional objectives may be specified according to the related sub-protocol. 
Primary Objective: 
• 
To determine the safety of DAY101 in combination with other therapies. 
• 
To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of 
DAY101 in combination with other therapies. 
Secondary Objectives: 
• 
To assess the efficacy of DAY101 in combination with other therapies by Response Evaluation 
Criteria in Solid Tumors (RECIST) version 1.1 or appropriate tumor response criteria. 
• 
To characterize the pharmacokinetic (PK) profile of DAY101 in combination with other therapies. 
• 
To characterize pharmacodynamic (PD) effects of DAY101 in combination with other therapies. 
Exploratory Objectives: 
• 
To evaluate the genomic profile of archival tumor biopsies or fresh tumor biopsies (if available) and 
circulating tumor DNA (ctDNA) from patients who will be treated with DAY101 in combination 
with other therapies. 
• 
To characterize pathway modulation and/or genomic alterations in tumor biopsies. 
• 
To characterize genomic alterations in ctDNA. 
Phase 2 
The Phase 2 objectives will apply to the investigation of DAY101 as monotherapy and in combination with 
other therapies. Additional objectives may be specified according to the relevant sub-protocol. 
Primary Objective: 
To evaluate the efficacy of DAY101 by RECIST version 1.1 or appropriate tumor response criteria as a 
monotherapy or in combination with other therapies 
Secondary Objectives: 

Day One Biopharmaceuticals, Inc.  (Day One) 
Clinical Protocol DAY101-102 
DAY101 
 
13 October 2022 
Protocol Amendment 2.0 Final 
Confidential & Proprietary 
Page 8 
• 
To assess the safety and tolerability of DAY101 as monotherapy or in combination with other 
therapies. 
• 
To assess additional efficacy parameters of DAY101 as monotherapy or in combination with other 
therapies. 
• 
To characterize the tumor responses observed with DAY101 as monotherapy or in combination with 
other targeted therapies. 
• 
To characterize the PK profile of DAY101 in combination with other therapies 
• 
To characterize the PD effects of DAY101 as monotherapy or in combination with other therapies. 
• 
To determine the relationship between PK and PD of DAY101 in combination with other therapies. 
Exploratory Objectives: 
• 
 
• 
To evaluate the genomic profile of archival tumor or fresh tumor biopsies and ctDNA from patients 
who will be treated with DAY101 as monotherapy or in combination with other therapies. 
• 
To characterize pathway modulation and/or genomic alterations from tumor biopsies. 
• 
To characterize genomic alterations in ctDNA. 
• 
• 
STUDY DESIGN: 
This is a Phase 1b/2, multi-center, open-label, umbrella study of patients 12 years of age with recurrent or 
progressive solid tumors with alterations in the key proteins of the RAS/RAF/MEK/ERK pathway, which will 
be referred to as the mitogen-activated protein kinase (MAPK) pathway. Patients with these alterations will be 
identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments 
of 1988 (CLIA) or other similarly certified laboratories. 
Based on the identified alterations in the key proteins of the MAPK pathway, patients may be offered the 
opportunity to participate in one or more sub-protocols within this umbrella study of DAY101 as 
monotherapy or in combination with other therapies. Enrollment will be based on the specific eligibility 
criteria described in each sub-protocol. 
Study DAY101-102 (master study) and sub-protocol consist of a screening period, a treatment period, a safety 
follow-up period, and a long-term follow-up period where survival, status and subsequent anticancer therapies 
are collected. 
DAY101 will be administered as specified in the sub-protocol. Additional dose schedules may be explored. 
Dose level(s), dose schedule(s), and cycle lengths for DAY101 as monotherapy or in combination with other 
therapies will be specified in each sub-protocol. Cycles will repeat, as specified in each sub-protocol, until 
disease progression, unacceptable toxicity, or withdrawal of consent, or death. Patients will undergo 
radiographic evaluation of their disease at baseline, the end of
 for 1 year and then
thereafter, or as specified in a given sub-protocol. Generally, response assessment will be performed 
according to RECIST version 1.1 for solid tumors. Alternative criteria may be used in specific disease 
settings, such as glioma, where response assessment will be assessed by Response Assessment in Neuro-
Oncology (RANO) criteria. Appropriate response criteria for tumors will be described in Appendix B and 
Appendix C. 
Patients who have radiographic evidence of disease progression may be allowed to continue DAY101 if, in 
the opinion of the Investigator, the patient is deriving clinical benefit from continuing study treatment, and 
continuation of treatment is approved by the Sponsor. 
Scheduled activities will be  outlined in the Schedule of Activities within each sub-protocol. 

Day One Biopharmaceuticals, Inc.  (Day One) 
Clinical Protocol DAY101-102 
DAY101 
 
13 October 2022 
Protocol Amendment 2.0 Final 
Confidential & Proprietary 
Page 9 
MAJOR ELIGIBILITY CRITERIA: 
 Eligibility criteria can be found within each sub-protocol. 
 
PLANNED SAMPLE SIZE: 
Total patients enrolled will depend on the sub-protocols included. For additional details, please see sub-
protocols. 
INVESTIGATIONAL DRUG: 
DAY101 for oral dosing is provided as a white to off-white 
 powder as an immediate-release 100 
mg tablet. The 100 mg tablets are red to yellowish-red oval tablets. All products are labeled DAY101. 
Additional therapies may be included. For further details, please see relevant sub-protocols.  
TREATMENT PROCEDURES: 
For treatment procedures, please refer to relevant sub-protocol. 
STUDY ASSESSMENTS: 
Standard monitoring for safety is outlined in the protocol and sub-protocols and will include physical 
examination and anthropometric measurements, Eastern Cooperative Oncology Group (ECOG)/Lansky score, 
clinical adverse events, laboratory variables (e.g., hematology and serum chemistries), electrocardiogram 
(ECG), echocardiogram (ECHO)/multi-gated acquisition (MUGA), and vital signs. 
Please see relevant sub-protocol for blood collection for PK assessments. 
Please see relevant sub-protocols for radiology review procedures and tumor specimen collection procedures. 
End of Study and Length of Study: 
Please refer to relevant sub-protocol for information on duration of each study and end of study information.  
STATISTICAL METHODS: 
Sample Size Considerations: 
Please see sub-protocols for sample size considerations relevant to each sub-protocol. Additional patients will 
be enrolled to account for any patients who are lost to follow-up or have no follow-up imaging. 
Analysis Methods: 
Efficacy Analyses 
All efficacy analyses will be performed on the full analysis set (FAS) population, which includes all patients 
who received at least 1 dose of study drug and have measurable disease as determined by the Investigator at 
baseline and have at least 1 follow-up imaging or radiographically confirmed progressive disease prior to the 
first imaging timepoint as outlined in Section 7.3.1.  
Overall response rate (ORR) as assessed by the proportion of patients with the best overall confirmed 
response of complete response (CR) or partial response (PR), according to the appropriate tumor response 
criteria as assessed by Investigator will be calculated and an exact confidence interval (CI) will be calculated. 
Duration of response (DOR) in patients with best overall response of CR or PR defined as from time of first 
tumor response to progression or date of data analysis, whichever occurs earlier as determined by the 
Investigator will be calculated. Progression free survival (PFS) is defined as the time from the date of the first 
dose of study drugs to the first occurrence of disease progression according to the appropriate tumor response 
criteria as assessed by Investigator, or death from any cause, whichever occurs earlier. Overall survival (OS) 
is defined as the period from the date of the first dose of study drugs until the date of death from any cause. 
Kaplan-Meier curves will be plotted for DOR, PFS, and OS. The timepoint for the analysis of response for 
Phase 2 studies’ primary efficacy objective will be when all patients have a minimum of 6 months of follow-
up. 

Day One Biopharmaceuticals, Inc.  (Day One) 
Clinical Protocol DAY101-102 
DAY101 
 
13 October 2022 
Protocol Amendment 2.0 Final 
Confidential & Proprietary 
Page 10 
Safety Analyses 
Safety will be evaluated by monitoring all adverse events, serious adverse events, adverse events of special 
interest, and abnormalities identified through physical examinations, vital signs, and laboratory assessments. 
Such events will be graded using the National Cancer Institute Common Terminology Criteria for Adverse 
Events, Version 5.0 (NCI CTCAE v5.0). All verbatim adverse event terms occurring on or after first study 
treatment will be mapped to Medical Dictionary for Regulatory Activities (MedDRA), and adverse event 
severity will be graded according to NCI CTCAE v5.0.  
Pharmacokinetic Analyses 
Plasma concentrations of DAY101 and other therapies (as applicable based on sub-protocols) will be 
determined with validated bioanalytical methods. Plasma concentrations will be analyzed at specified time 
points in order to generate PK parameters as appropriate and will be described in more detail in the sub-
protocol(s). Summary statistics will be generated as appropriate. 

Day One Biopharmaceuticals, Inc.  (Day One) 
Clinical Protocol DAY101-102 
DAY101 
13 October 2022 
Protocol Amendment 2.0 Final 
Confidential & Proprietary 
Page 11 
SCHEDULE OF ACTIVITIES 
Scheduled activities will be performed in as outlined within each sub-protocol (see sub-
protocol section, Schedule of Activities). Study procedures are included in this Master 
Protocol, Section 6. 

Day One Biopharmaceuticals, Inc.  (Day One) 
Clinical Protocol DAY101-102 
DAY101 
 
13 October 2022 
Protocol Amendment 2.0 Final 
Confidential & Proprietary 
Page 12 
TABLE OF CONTENTS 
PROTOCOL AMENDMENT SUMMARY OF CHANGES ...................................... 3 
SYNOPSIS .................................................................................................................. 7 
SCHEDULE OF ACTIVITIES .................................................................................. 11 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS .............................. 18 
1. 
INTRODUCTION .................................................................................. 22 
1.1. 
Background on Disease .......................................................................... 22 
1.1.1. 
Cancer Physiology .................................................................................. 22 
1.1.2. 
Advanced Solid Tumors ......................................................................... 23 
1.1.3. 
Current Therapies ................................................................................... 24 
1.2. 
Background on DAY101 ........................................................................ 24 
1.2.1. 
DAY101 Nonclinical Data ..................................................................... 24 
1.2.2. 
DAY101 Clinical Data ........................................................................... 25 
1.2.2.1. 
Clinical Pharmacokinetics ...................................................................... 27 
1.2.2.2. 
Clinical Efficacy ..................................................................................... 27 
1.2.2.3. 
Clinical Safety ........................................................................................ 29 
1.3. 
Study Rationale and Dose Justification .................................................. 32 
1.3.1. 
Study Rationale ....................................................................................... 32 
1.3.2. 
Justification for Dose .............................................................................. 33 
1.3.3. 
Drug Metabolism for DAY101 ............................................................... 36 
1.3.4. 
Benefit/Risk ............................................................................................ 36 
2. 
STUDY OBJECTIVES .......................................................................... 38 
3. 
INVESTIGATIONAL PLAN ................................................................. 42 
3.1. 
Study Design ........................................................................................... 42 
3.1.1. 
End of Study and Length of Study ......................................................... 43 
3.1.2. 
Number of Patients ................................................................................. 43 
3.2. 
Investigational Sites ................................................................................ 43 
4. 
SELECTION OF STUDY POPULATION ............................................ 44 
5. 
TREATMENT ........................................................................................ 45 
5.1. 
Investigational Product ........................................................................... 45 
5.2. 
DAY101 Administration ........................................................................ 45 
5.2.1. 
General Dosing Instructions ................................................................... 45 

Day One Biopharmaceuticals, Inc.  (Day One) 
Clinical Protocol DAY101-102 
DAY101 
 
13 October 2022 
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5.2.2. 
Dose-Limiting Toxicity .......................................................................... 45 
5.2.3. 
Dose Modifications ................................................................................. 45 
5.2.4. 
Management of Treatment-Related Events ............................................ 45 
5.3. 
Removal of Patients from Therapy or Assessment ................................. 46 
5.4. 
Prior and Concomitant Medications ....................................................... 46 
5.4.1. 
General .................................................................................................... 46 
5.4.2. 
Allowed Concomitant Medications ........................................................ 46 
5.4.3. 
Prohibited Concomitant Medications ..................................................... 46 
5.4.4. 
Palliative Radiotherapy ........................................................................... 47 
5.4.5. 
Concurrent Surgery ................................................................................. 47 
5.5. 
Preparation, Handling, Storage and Accountability ............................... 47 
6. 
TESTS AND EVALUATIONS .............................................................. 48 
6.1. 
Screening ................................................................................................ 48 
6.2. 
Enrollment .............................................................................................. 48 
6.3. 
Medical History and Malignancy History .............................................. 49 
6.4. 
Archival Tumor Samples ........................................................................ 49 
6.5. 
Freshly Acquired Tumor Samples for Pharmacodynamic Analysis ....... 49 
6.6. 
Circulating Tumor DNA (ctDNA) Samples: Blood ............................... 49 
6.7. 
Physical Examination ............................................................................. 49 
6.8. 
Eastern Cooperative Oncology Group Status/Lansky Performance Status
 ................................................................................................................ 49 
6.9. 
Assessment of Change in Pubertal Development (Tanner Stage) .......... 49 
6.10. 
Vital Signs .............................................................................................. 50 
6.11. 
Ophthalmology Examination .................................................................. 50 
6.12. 
Visual Symptom Assessment ................................................................. 50 
6.13. 
Dermatologic Examination ..................................................................... 50 
6.14. 
Neurologic Examination ......................................................................... 51 
6.15. 
Height and Bone Age .............................................................................. 51 
6.16. 
Cardiac Function ..................................................................................... 51 
6.16.1. 
Electrocardiograms ................................................................................. 51 
6.16.2. 
Echocardiogram/Multiple-Gated Acquisition ........................................ 51 
6.17. 
Laboratory Tests ..................................................................................... 51 
6.17.1. 
Pregnancy Test ........................................................................................ 52 

Day One Biopharmaceuticals, Inc.  (Day One) 
Clinical Protocol DAY101-102 
DAY101 
 
13 October 2022 
Protocol Amendment 2.0 Final 
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6.17.2. 
Hematology ............................................................................................. 52 
6.17.3. 
Serum Chemistries .................................................................................. 52 
6.17.4. 
Coagulation Panel ................................................................................... 52 
6.17.5. 
Thyroid Function Tests ........................................................................... 52 
6.18. 
Pharmacokinetic Samples: Blood ........................................................... 52 
6.19. 
Disease Assessment ................................................................................ 52 
6.19.1. 
Tumor Measurements ............................................................................. 52 
6.19.1.1. 
Collection of Radiographic Studies for Independent Review ................ 53 
6.20. 
Telephone/Telemedicine Visit ................................................................ 53 
6.21. 
Survival Status ........................................................................................ 53 
6.22. 
Study Drug Administration and Dosing Diary ....................................... 53 
6.23. 
Concomitant Medication ........................................................................ 53 
6.24. 
End of Treatment Visit ........................................................................... 53 
6.25. 
Safety Follow-up Visit ............................................................................ 53 
6.26. 
Long-Term Follow-up ............................................................................ 54 
6.27. 
Force Majeure Flexibility ....................................................................... 54 
7. 
PLANNED ANALYSES ........................................................................ 55 
7.1. 
Analysis Populations .............................................................................. 55 
7.2. 
Determination of Sample Size ................................................................ 55 
7.3. 
Statistical Methods .................................................................................. 55 
7.3.1. 
Efficacy Analyses ................................................................................... 55 
7.3.2. 
Safety Analyses ...................................................................................... 56 
7.3.2.1. 
Deaths ..................................................................................................... 56 
7.3.2.2. 
Laboratory Values .................................................................................. 56 
7.3.2.3. 
Vital Signs .............................................................................................. 57 
7.3.2.4. 
Concomitant Medications ....................................................................... 57 
7.3.3. 
Pharmacokinetic Analyses ...................................................................... 57 
8. 
ADVERSE EVENTS .............................................................................. 58 
8.1. 
Adverse Events, Adverse Events of Special Interest, and Serious 
Adverse Events ....................................................................................... 58 
8.1.1. 
Time Period and Frequency for Collecting Adverse Event, Adverse 
Events of Special Interest, and Serious Adverse Event Information ...... 58 

Day One Biopharmaceuticals, Inc.  (Day One) 
Clinical Protocol DAY101-102 
DAY101 
 
13 October 2022 
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8.1.2. 
Method of Detecting Adverse Events, Adverse Events of Special 
Interests, and Serious Adverse Events .................................................... 59 
8.1.3. 
Follow-up of Adverse Events, Adverse Events of Special Interests, and 
Serious Adverse Events .......................................................................... 59 
8.1.4. 
Regulatory Reporting Requirements for Any SAEs and Non-Serious 
AESIs Occurring During this Study Must Be Reported as Follows: ...... 59 
8.1.5. 
Pregnancy or Combination Partner ......................................................... 60 
8.1.6. 
Death Events ........................................................................................... 60 
8.2. 
Data Monitoring Committee (DMC) ...................................................... 61 
8.2.1. 
Risk Management ................................................................................... 61 
8.2.2 
Continuous Review of Safety Data ......................................................... 61 
8.3. 
Stopping Rules ........................................................................................ 61 
8.4. 
Grading and Intensity of Adverse Events ............................................... 62 
8.5. 
Relationship to Study Drug .................................................................... 63 
8.6. 
Serious Adverse Event Follow-up .......................................................... 63 
9. 
STUDY ADMINISTRATION ............................................................... 64 
9.1. 
Regulatory and Ethical Considerations .................................................. 64 
9.1.1. 
Regulatory Authority Approval .............................................................. 64 
9.1.2. 
Ethics Approval ...................................................................................... 64 
9.1.3. 
Patient Informed Consent and Pediatric Assent ..................................... 64 
9.1.4. 
Investigator Reporting Requirements ..................................................... 65 
9.2. 
Data Management ................................................................................... 65 
9.3. 
Study Monitoring .................................................................................... 66 
9.4. 
Termination ............................................................................................. 66 
9.5. 
Records Retention ................................................................................... 67 
9.6. 
Confidentiality of Information ................................................................ 67 
10. 
REFERENCES ....................................................................................... 68 
 

Day One Biopharmaceuticals, Inc.  (Day One) 
Clinical Protocol DAY101-102 
DAY101 
 
13 October 2022 
Protocol Amendment 2.0 Final 
Confidential & Proprietary 
Page 16 
LIST OF TABLES 
Table 1: 
Confirmed Best Overall Response and Overall Response Rate (Study 
FIREFLY-1/PNOC026) .......................................................................... 29 
Table 2: 
TEAEs Reported for ≥ 10% of Adult Patients with Advanced Solid 
Tumors Overall (Safety Population) (Study C28001) ............................ 30 
Table 3: 
Grade ≥ 3 Adverse Events Occurring in ≥2 Patients by Preferred Term 
(Study
) ................................................................................... 31 
Table 4: 
Incidence and Percentage of Treatment-Emergent and Treatment-Related 
AEs (Study FIREFLY-1/PNOC026) ...................................................... 32 
Table 5: 
Phase 1b Study Objectives and Endpoints .............................................. 38 
Table 6: 
Phase 2 Study Objectives and Endpoints ................................................ 40 
Table 7: 
Population Definitions ............................................................................ 55 
Table 8: 
Summary of AE Collection Periods ....................................................... 58 
Table 9: 
NCI CTCAE Definitions of Severity for Adverse Reactions ................. 62 
Table 10: ECOG Performance Status ..................................................................... 71 
Table 11: Lansky Performance Score (< 16 years old) ........................................... 71 
Table 12: Overall Assessment by RECIST 1.1 at Each Time Point ....................... 75 
Table 13: Best Overall Assessment by RECIST 1.1 ............................................... 76 
Table 14: RANO Response Criteria Incorporating MRI and Clinical Factor ........ 77 
 
 
LIST OF FIGURES 
Figure 3: 
Study Design Schema ............................................................................. 43 
 

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LIST OF APPENDICES 
Appendix A: Eastern Cooperative Oncology Group (ECOG) Performance Status 
and Lansky Performance Score ......................................................... 71 
Appendix B: Response Evaluation Criteria in Solid Tumors: Revised RECIST 
Guideline (Version 1.1) ..................................................................... 72 
Appendix C: Response Assessment in Neuro-Oncology (RANO) Criteria for 
Primary CNS Malignancies ............................................................... 77 
Appendix D: Specimen and Data Use ..................................................................... 79 
Appendix E: List of Research Uses of Tissue, Plasma and Clinical Data .............. 80 
Appendix F: Contraceptive Guidance and Collection of Pregnancy Information .. 83 
Appendix G: Adverse Events. Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting .............................................. 86 
Appendix H: Blood Pressure by Height and Age .................................................... 91 
Appendix I: 
Serum Creatinine Clearance Calculation ........................................... 96 
Appendix J: 
Body Surface Area (BSA) Calculation .............................................. 97 

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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation  
or Term 
Definition 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
AUC0-24 
area under the concentration-time curve over the last 24-h dosing interval 
AUC0-t 
area under the concentration-time curve from time zero to t 
BBB 
blood brain barrier 
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 
BUN 
blood urea nitrogen 
C 
cycle 
CI 
confidence interval 
CL/F 
apparent oral clearance of drug 
CLIA 
Clinical Laboratory Improvement Amendments 
Cmax 
maximum drug concentration 
CNS 
central nervous system 
CPK 
creatine phosphokinase 
CR 
complete response 
CRAF 
v-raf murine sarcoma viral oncogene homolog C  
CRC 
colorectal cancer 
CRF 
case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
ctDNA 
circulating tumor DNA 
CVA 
cerebrovascular accident 
CYP 
cytochrome P450 
D 
Day 
DLT 
dose-limiting toxicity 
DMC 
Data Monitoring Committee 
DOR 
duration of response 
DRESS 
drug reaction with eosinophilia and systemic symptoms 
DSMB 
Data Safety Monitoring Board 

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Abbreviation  
or Term 
Definition 
EC 
European Commission 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ECHO 
echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EMA 
European Medicines Agency 
EOT 
End of Treatment 
ERK 
extracellular signal-related kinase 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FFPE 
formalin-fixed, paraffin-embedded 
FIH 
First-In-Human 
FISH 
fluorescence in situ hybridization 
GCP 
Good Clinical Practices 
GDP 
guanosine diphosphate 
GTP 
guanosine triphosphate 
HGG 
high-grade glioma 
HREC 
Human Research Ethics Board 
IB 
Investigator’s Brochure 
IC50 
inhibitory concentration equal to 50% maximal response 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
INR 
international normalized ratio. 
IRB 
Institutional Review Board 
IRC 
independent review committee 
IRT 
interactive response technology 
KRAS 
Kirsten rat sarcoma viral oncogene homologue 
LE 
Long Evans 
LTFU 
long-term follow-up 
LVEF 
left ventricular ejection fraction 
LGG 
low-grade glioma 
MAPK 
mitogen-activated protein kinase 
MedDRA 
Medical Dictionary for Regulatory Activities 

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Abbreviation  
or Term 
Definition 
MEK 
mitogen-activated protein kinase kinase 
MRI 
magnetic resonance imaging 
mRNA 
micro RNA 
MTD 
maximum tolerated dose 
MUGA 
Multiple-gated acquisition 
NCI 
National Cancer Institute 
NRAS 
neuroblastoma RAS viral oncogene homologue 
NSCLC 
non-small cell lung cancer 
NTRK genes 
neurotrophic tyrosine kinase receptor genes 
OAT 
organic anion transporter 
OATP 
organic anion transporting polypeptides  
OCT 
organic cation transporter 
OPG 
optic pathway glioma 
ORR 
overall response rate 
OS 
overall survival 
PBPK 
physiological based pharmacokinetic modeling and simulation 
PCR 
polymerase chain reaction 
PD 
pharmacodynamic(s) 
PfR 
powder-for-reconstitution 
PFS 
progression-free survival 
P-gp 
p-glycoprotein 
PK 
pharmacokinetic(s)  
pLGG 
pediatric low-grade glioma 
PO 
per os, orally 
PR 
partial response 
PTT 
activated prothrombin time 
Q2D 
every other day 
QD 
once-daily 
QOL 
quality of life 
QTc 
QT interval corrected for heart rate 
QTcF 
QT interval corrected for heart rate by Fridericia's formula 
QW 
once weekly 
RAF 
rapidly accelerated fibrosarcoma 
RANO 
Response Assessment in Neuro-Oncology 
RAS 
rat sarcoma virus 

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Abbreviation  
or Term 
Definition 
REB 
Research Ethics Board 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
recommended Phase 2 dose 
RVO 
retinal vein occlusion 
SAP 
statistical analysis plan 
SAE 
serious adverse event 
SCC 
squamous cell carcinoma 
SD 
stable disease 
SJS 
Stevens Johnsons syndrome 
T3 
triiodothyronine 
T4 
tetraiodothyronine 
t1/2  
half-life 
TEAE 
treatment-emergent adverse event  
TSH 
thyroid stimulating hormone 
TTR 
time to response 
ULN 
upper limit of normal 
US 
United States 
WHO 
World Health Organization 

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1. 
INTRODUCTION 
DAY101 is an oral, selective, small-molecule, Type-II pan-rapidly accelerated fibrosarcoma 
(RAF) kinase inhibitor that is being developed by Day One Biopharmaceuticals, Inc. 
(Day One, the Sponsor) as monotherapy for the treatment of solid tumors with RAF fusions, 
RAF amplifications, and v-raf murine sarcoma viral oncogene homolog B (BRAF) mutations 
in adult and pediatric populations. 
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 affecting adult and pediatric patients, including melanoma, non-small 
cell lung cancer (NSCLC), and colorectal cancer (CRC) (Yaeger and Corcoran 2019). Across 
human tumors, rat sarcoma virus (RAS) mutations occur in 10–30%, BRAF in 6%, mitogen-
activated protein kinase kinase (MEK) in < 1% of cases, and extracellular signal-related 
kinase (ERK) mutations are exceptionally rare (Yaeger and Corcoran 2019, Prior et al. 2020). 
One of the most frequently altered genes in this pathway is BRAF, in which 90% of the 
mutations consist of the BRAF V600 point mutation (including amino acid substitutions 
V600E/K/D/R/M). This point mutation leads to both increased BRAF kinase activity that is 
independent of extracellular stimuli or RAS-guanosine triphosphate (GTP) and constitutive 
signaling that drives cell proliferation and tumor growth (Davies et al. 2002). Currently, the 
United States (US) Food and Drug Administration (FDA) has approved 3 agents that inhibit 
BRAF V600E/K: vemurafenib, dabrafenib, and encorafenib. 
Beyond BRAF V600 point mutations, additional genomic alterations including non-V600 
point mutations, BRAF fusions, and in-frame deletions have also been reported in human 
cancers (Ross et al. 2016). Non-V600 BRAF mutations can be found located in the activation 
segment, P-loop, catalytic loops, and DFG motif. 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. These alterations generally drive 
aberrant expression and constitutive activation of the kinase and downstream signaling 
pathway (Lu et al. 2017). 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). 
Beyond BRAF, other common genetic alterations can lead to the dysregulation of the MAPK 
pathway, such as RAS mutation. Oncogenic RAS mutations occur at hot spots that interfere 
with normal RAS regulation and function, such as the guanosine diphosphate (GDP)–GTP 
molecular switch, which leads to a constitutively active GTP-bound protein. Among RAS 
genes, Kirsten rat sarcoma viral oncogene homologue (KRAS) is most frequently mutated in 
cancer (85%), followed by NRAS (11%) and HRAS (5%) (Hobbs et al. 2016). 

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Targeting RAS has been challenging due to the difficulty in disrupting the protein:protein 
interactions that underlie its activation and function, although recent success has been 
observed with sotorasib (Lumakras™), an irreversible covalent inhibitor of KRAS G12C, in 
patients with advanced solid tumors harboring the KRAS G12C mutation (Mattingly et al. 
2013, Hong et al. 2020). While sotorasib was recently approved for adult patients with 
NSCLC whose tumors harbor KRAS G12C, there is a need to develop KRAS inhibitors that 
impact beyond KRAS G12C mutation. Despite early success, early data with KRAS-G12C 
inhibitors have demonstrated mixed sensitivity of cell lines expressing KRAS G12C, with 
many cell lines able to sustain downstream RAS effector signaling with adaptive feedback 
through wild-type RAS proteins (Lito et al. 2016). For NRAS mutant tumors, single-agent 
MEK inhibitors such as binimetinib have been evaluated for the treatment of NRAS mutant 
melanoma in a Phase 3 study. Results of binimetinib versus dacarbazine in NRAS mutant 
melanoma have shown modest effect on tumor response (overall response rate [ORR] 15%) 
in NRAS mutant melanoma which did not translate into clinical benefit in overall survival 
(OS) (Dummer et al. 2017). Other treatments are being explored combining MEK inhibitors 
with other targets for both NRAS and HRAS positive cancers (Johnson and Puzanov, 2015, 
Boespflug et al. 2017, Scott et al. 2016). In summary, additional therapies or therapeutic 
approaches are needed to target tumors harboring mutations in RAS. 
Recurrent rearrangements in RAF have been found to occur in advanced prostate cancers, 
gastric cancers, and melanoma (Palanisamy et al. 2010). Beyond BRAF fusions, 
CRAF/RAF1 fusions have also been detected in melanoma and low-grade glioma and while, 
rare, these can also constitutively activate the MAPK pathway (Ryall et al. 2020, Williams et 
al. 2020). Thus, inhibition of CRAF/RAF1 could be a therapeutic strategy to target tumors 
harboring RAF fusions.  
Lastly, emerging research has identified a unique subset of urothelial tumors with focal 
amplification of the RAF1 kinase gene. RAF1-amplified tumors have activation of the 
RAF/MEK/ERK signaling pathway and exhibit a luminal gene expression pattern. Genetic 
studies demonstrate that RAF1-amplified tumor cell lines are dependent upon RAF1 activity 
for survival. Furthermore, bladder tumors with HRAS activating mutations are dependent on 
RAF1-mediated signaling and are sensitive to RAF1-targeted therapy, such as with a pan-
RAF inhibitor. Together, these data identify RAF1 and HRAS activation as a novel 
dependency in a subset comprising nearly 20% of urothelial tumors and suggest that 
targeting RAF1-mediated signaling represents a rational therapeutic strategy (Bekele et al. 
2021). 
1.1.2. 
Advanced Solid Tumors 
Cancer is second leading cause of death in adults in the West (US, Europe) and the leading 
cause of death in the East (China, Japan, and Korea). In the United States in 2017, 
approximately 1 in 5 deaths are due to cancer. Although the overall 5-year survival rate for 
all cancers has been improving (67%, from SEER Cancer Stats, 2017), for those with 
advanced metastatic disease, their relative 5-year survival rates are poor, generally 30% or 
less. These data indicate that there is a great unmet need for additional anticancer agents with 
novel mechanisms of action. 

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(pLGG). Study conduct for a relative 
 study in 
healthy subjects (Study
 has also been completed. 
Study C28001 was a Phase 1 First -In -Human (FIH) 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 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 for 
whom standard therapies had failed. 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 CRC or advanced NSCLC (with either KRAS 
exon 2 mutations or non-V600 BRAF mutations). Details of this study can be found in the 
DAY101 IB. 
Study 
 
Study

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Study FIREFLY-1/PNOC026 
Sponsor is currently conducting a pivotal Phase 2, open-label study to evaluate the safety and 
efficacy of DAY101 monotherapy in the treatment of RAF-altered, recurrent, or progressive 
low-grade gliomas or advanced solid tumors. This study is expected to enroll approximately 
140 pediatric and young adult patients 6 months to 25 years of age. This study includes 3 
arms. Arm 1 (N = 60) serves as the main cohort to evaluate DAY101 in the treatment of 
patients with recurrent or progressive low-grade glioma harboring a known activating BRAF 
alteration. Study results of Arm 1 will be the basis of DAY101’s initial regulatory license 
application. Arm 2 (N = 60) is enrolling a similar patient population to Arm 1 based on the 
recommendation of a Data Safety Monitoring Board (DSMB) and is aimed to provide 
continuous access to DAY101 prior to commercial availability. In addition, Arm 3 is 
enrolling  patients with advanced solid tumors harboring RAF fusions (e.g., BRAF or 
CRAF/RAF1 fusions).  
As of 11 April 2022, Arm 1 has fully accrued and was closed to enrollment. The study is 
ongoing.  
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 
Antitumor activity was most evident in the BRAF mutation -positive treatment -naïve 
expansion melanoma cohort using 200 mg Q2D regimen (ORR: 8/16 patients, 50% [95% 
confidence interval (CI) 25, 75]; median duration of response (DOR) [partial response (PR) 
in 8 patients]: 6.0 months [95% CI: 3.7, not estimable]; median progression-free survival 
(PFS): 5.7 months [95% CI: 1.9, 14.3]). A PR was also reported in 1 of 6 patients in the 
BRAF mutation -positive previously treated cohort (ORR: 17%; 95% CI: < 1, 64). Another 
PR was reported in 1 of 14 patients in the NRAS mutation-positive MAK kinase treatment 
naïve cohort (ORR: 7%; 95% CI: < 1, 34). 
Further details of the efficacy data from C28001 can be found in the DAY101 IB. 
Study 
 

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Study FIREFLY-1/PNOC026 
As of 14 April 2022, 25 patients had at least 2 post-baseline radiographic assessments 
(performed every 3 cycles). Out of 25 patients dosed, 3 patients were determined by the 
independent review committee (IRC) to lack measurable lesion(s) meeting the 
RANO-high-grade glioma (HGG) criteria definition for measurability at baseline (Wen et al. 
2010) and were thus excluded from the efficacy analysis (n = 22).  
Response data presented in the tables below are based on evaluation by IRC using 
RANO-HGG criteria. Table 1 includes best overall confirmed response by BRAF alteration. 
Of these 22 patients, 13 (59.1%) have achieved a confirmed partial response. Additionally, 
one patient with a best overall response (BOR) of stable disease achieved an unconfirmed 
partial response (reduction of 50% from baseline) at the most recent radiographic assessment 
and remains on treatment. In addition, duration of response ranged from approximately 3 to 8 
months. As of the data cutoff of 14 April 2022, all responses were ongoing. 
Of the 22 patients included in the analysis, 5 patients have discontinued, 3 due to progressive 
disease and 2 due to withdrawal of consent. No patients with a documented response 
(confirmed or unconfirmed) have discontinued due to toxicity or disease progression. 

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Table 1: 
Confirmed Best Overall Response and Overall Response Rate (Study 
FIREFLY-1/PNOC026) 
Best Overall 
Response,  
N (%) 
BRAF Mutation 
n = 2 
BRAF Fusiona 
n = 20 
Total Efficacy 
Evaluable 
N = 22 
CR 
0 
0 
0 
PR 
2 (100.0) 
11 (55.0) 
13 (59.1) 
unconfirmed PRb 
0 
1 (4.5) 
1 (4.5) 
SD 
0 
6 (30.0) 
6 (27.3) 
PD 
0 
2 (10.0) 
2 (9.1) 
Overall Response Rate 
(95% CI)c 
100% (15.8–100) 
60.0% (36.1–80.9) 
63.6% (40.7–82.8) 
Abbreviations: CI, confidence interval; CR, complete response; FISH, fluorescence in situ hybridization; PD, 
progressive disease; PR, partial response; SD, stable disease. 
a. BRAF Fusion includes KIAA1549:BRAF fusion as identified by next-generation sequencing or dual-probe FISH and 
BRAF rearrangements as identified by break-apart FISH.  
b. One patient had an unconfirmed PR at the time of data cutoff, where the confirmation scan was not read by IRC.  
c. Includes patients with best overall response of CR, PR, and unconfirmed PR. 
Source: DAY101 Investigator’s Brochure  
1.2.2.3. 
Clinical Safety 
Study C28001 
Over the life of this study, which was completed on 16 October 2018, 110 patients were 
administered at least 1 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 1 
dose of DAY101 on a QW dose schedule (20 in the QW dose escalation phase [3 in the 
400 mg cohort, 13 in the 600 mg cohort, and 4 in the 800 mg cohort] and 19 dosed at 600 mg 
QW in the expansion phase). The monotherapy treatment of 149 adults has provided a 
comprehensive database of safety information. 
Of the 149 patients treated, all had at least 1 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 Investigator’s Brochure. 

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Table 2: 
TEAEs Reported for ≥ 10% of Adult Patients with Advanced Solid 
Tumors Overall (Safety Population) (Study C28001)  
Preferred Term  
Dose-Expansion Phase 
Q2D Total 
N = 80 
n (%) 
QW Total  
N = 19 
n (%) 
Total 
N = 99 
n (%) 
Patients with at least 1 
Treatment-Emergent AE 
80 (100) 
19 (100) 
99 (100) 
Fatigue 
34 (43) 
9 (47) 
43 (43) 
Anaemia 
33 (41) 
4 (21) 
37 (37) 
Constipation 
30 (38) 
4 (21) 
34 (34) 
Nausea 
29 (36) 
5 (26) 
34 (34) 
Rash maculo-papular 
30 (38) 
3 (16) 
33 (33) 
Dyspnoea 
24 (30) 
4 (21) 
28 (28) 
Blood creatine phosphokinase 
increased 
23 (29) 
1 (5) 
24 (24) 
Myalgia 
20 (25) 
3 (16) 
23 (23) 
Vomiting 
16 (20) 
3 (16) 
19 (19) 
Decreased appetite 
14 (18) 
4 (21) 
18 (18) 
Pruritus 
16 (20) 
1 (5) 
17 (17) 
Pyrexia 
14 (18) 
3 (16) 
17 (17) 
Dysgeusia 
16 (20) 
1 (5) 
17 (17) 
Periorbital oedema 
14 (18) 
2 (11) 
16 (16) 
Aspartate aminotransferase 
increased 
16 (20) 
0 
16 (16) 
Arthralgia 
11 (14) 
4 (21) 
15 (15) 
Oedema peripheral 
15 (19) 
0 
15 (15) 
Diarrhoea 
13 (16) 
1 (5) 
14 (14) 
Dermatitis acneiform 
12 (15) 
2 (11) 
14 (14) 
Pain in extremity 
14 (18) 
0 
14 (14) 
Hair colour changes 
13 (16) 
1 (5) 
14 (14) 
Headache 
11 (14) 
2 (11) 
13 (13) 
Back pain 
12 (15) 
1 (5) 
13 (13) 
Cough 
10 (13) 
2 (11) 
12 (12) 
Abdominal pain 
9 (11) 
1 (5) 
10 (10) 
Study C28002 
Study C28002 
was an open‑label study designed to evaluate DAY101 in 
combination with MLN0128, alisertib, paclitaxel, cetuximab, or irinotecan. During both dose 
escalation and dose expansion where 81 patients were enrolled (71 patients in the 
dose-escalation phase and 10 patients in the dose-expansion phase), the most commonly 
reported TEAE was hypophosphatemia (41 patients [58%] and 7 patients [70%], 
respectively). Grade 3 or higher TEAEs were reported for 59 patients (83%) during dose 

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escalation and 9 patients (90%) during dose expansion. Overall, the most commonly reported 
Grade ≥ 3 TEAEs were hypophosphatemia, reported for 27 patients (38%) during dose 
escalation and 6 patients (60%) during dose expansion, and anemia, reported for 19 patients 
(27%) during dose escalation and 4 patients (40%) during dose expansion. More details can 
be found in the DAY101 IB. 
Study
Table 3: 
Grade ≥ 3 Adverse Events Occurring in ≥2 Patients by Preferred Term 
(Study
   
Sponsor Modified Term 
CTCAE Grade 
 
Total (N =
 N (%) 
Vomiting 
Hypophosphatemia 
Rash maculopapular 
CPK increased 
Hydrocephalus 
Fatigue 
Nausea 
Device related infection 
Headache 
Abbreviations: CPK, creatine phosphokinase; CTCAE, Common Terminology Criteria for Adverse Events; 
N, number. 
Source: DAY101 Investigator’s Brochure  
The 
 study has completed patient accrual, and follow-up for enrolled patients is 
ongoing as of the date of this protocol. 
Study FIREFLY-1/PNOC026 
Safety data from the first 25 patients enrolled on FIREFLY-1/PNOC026 are summarized in 
Table 4 below. DAY101 is well-tolerated, and most treatment-emergent AEs were deemed 
Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or 2. The most 
common CTCAE Grade ≥ 3 treatment-emergent AEs, , were rash (3 patients [12%]) anemia, 
blood CPK increase (2 patients each [8%]). and vomiting (1 patient [4%]). Seven patients 
(28%) required dose modification due to treatment-related AEs; however, no patient 
discontinued treatment due to AE at the time of data cutoff.  

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Table 4: 
Incidence and Percentage of Treatment-Emergent and 
Treatment-Related AEs (Study FIREFLY-1/PNOC026) 
Preferred term, N (%) 
Treatment-emergent AEs 
Treatment-related AEs 
Any Grade 
CTCAE 
Grade ≥ 3 
Any Grade 
CTCAE 
Grade ≥ 3 
Blood creatine phosphokinase increased 
20 (80) 
2 (8) 
18 (72) 
2 (8) 
Hair color changes 
17 (68) 
- 
17 (68) 
- 
Anemia 
14 (56) 
3 (12) 
10 (40) 
2 (8) 
Aspartate aminotransferase increased 
14 (56) 
- 
12 (48) 
- 
Vomiting 
14 (56) 
2 (8) 
6 (24) 
1 (4) 
Rasha 
13 (52) 
3 (12) 
13 (52) 
3 (12) 
Blood lactate dehydrogenase increased 
12 (48) 
- 
9 (36) 
- 
Headache 
10 (40) 
- 
3 (12) 
- 
Dry skin 
9 (36) 
- 
7 (28) 
- 
Epistaxis 
9 (36) 
- 
4 (16) 
- 
Constipation 
8 (32) 
- 
5 (20) 
- 
Hypocalcemia 
8 (32) 
- 
6 (24) 
- 
Nausea 
8 (32) 
- 
3 (12) 
- 
Alanine aminotransferase increased 
7 (28) 
1 (4) 
4 (16) 
1 (4) 
Fatigue 
7 (28) 
- 
7 (28) 
- 
Abbreviations: AE, adverse event; INR, international normalized ratio. 
a. 
Includes maculopapular and erythematous rash 
Source: DAY101 Investigator’s Brochure  
1.3. 
Study Rationale and Dose Justification 
1.3.1. 
Study Rationale 
In the MAPK signaling pathway, kinase inhibitor-mediated inhibition of oncogenic driver 
alterations (such as mutations in BRAF, KRAS, NRAS, or RAF fusions) can lead to an 
antitumor response due to “addiction” of the cancer to the activated pathway. However, 
acquired resistance can occur due to multiple adaptive mechanisms including relief of 
negative feedback that can drive ERK reactivation (Johnson et al. 2014; Johnson and 
Puzanov 2015). Interestingly, inhibition of 2 nodes of the MAPK pathway such as 
combination of BRAF and MEK inhibition has been shown to provide more lasting clinical 
benefit compared to inhibition of only BRAF alone (Long et al. 2017). Therefore, we 
propose in this “umbrella design” Master Protocol to evaluate DAY101, a Type-II RAF 
inhibitor that can bind both monomeric and dimeric forms of RAF, as a therapeutic 
monotherapy and in combination in order to drive deeper and more durable responses in 
biomarker-defined cancers. Sub-protocols under this Master Protocol will explore the use of 

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Study
Study 
  

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Because DAY101 is an experimental medicine, it is possible that unforeseen, unknown, or 
unanticipated drug reactions and toxicities may occur. Based on prior clinical studies in 
adults, frequently reported adverse events observed  with DAY101 monotherapy at the QW 
dosing regimen were fatigue (50% all grade, 5% Grade 3), rash (13%, primarily Grade 1 and 
2), anemia (30% of patients, all Grade; 10% of patients, Grade ≥ 3), and gastrointestinal 
events (all Grades 1 and 2). Other notable laboratory abnormalities were aspartate 
aminotransferase (AST) elevation, and increased creatine phosphokinase levels. In pediatric 
studies to date, the safety profile of DAY101 at the QW dosing regimen has been consistent 
with adult clinical trial data. However, as detailed below, this clinical protocol is designed to 
mitigate risks to patients primarily through eligibility criteria, dose modifications for 
toxicities, guidelines for toxicity recognition and management of common events. A detailed 
plan for careful safety monitoring, systematic review of adverse events, monitoring and 
reporting of serious adverse events (SAEs) and adverse events of special interest (AESIs), 
evaluation of PK, and active pharmacovigilance review to assess for safety signals or trends 
has been implemented. 
Patients, both adults and adolescents, with aberrations in the key proteins of the MAPK 
pathway who have exhausted standard-of-care treatment represent populations with high 
unmet need as discussed in Section 1.1. Therefore, there is an urgent need to identify new 
Type II pan-RAF inhibitors that can inhibit these both RAF monomers and dimers and limit 
AEs associated with these agents. 
Taken together, these considerations indicate the benefit/risk ratio for treatment with 
DAY101 to be favorable. 
Additional therapies in combination with DAY101 may be investigated based on the 
scientific and therapeutic hypotheses outlined above. For further details related to benefit/risk 
with the combination, please see relevant sub-protocols. 

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2. 
STUDY OBJECTIVES 
Specific objectives and corresponding endpoints for the master study and sub-studies are 
outlined in Table 5 and Table 6 below. Additional objectives and endpoints may be specified 
according to the relevant sub-protocol. 
The Phase 1b objectives will only apply to sub-studies of DAY101 in combination with other 
therapies (Table 5). 
The Phase 2 objectives will apply to the investigation of DAY101 as monotherapy and in 
combination with other therapies. Additional objectives will be specified according to the 
relevant sub-protocol (Table 6). 
Table 5: 
Phase 1b Study Objectives and Endpoints 
PRIMARY OBJECTIVE AND ENDPOINTS IN PHASE 1B 
OBJECTIVE 
ENDPOINTS 
To determine the safety of DAY101 in 
combination with other therapies. 
• 
Incidence and severity of adverse events, with severity 
determined according to National Cancer Institute 
Common Terminology Criteria for Advanced Tumours 
(NCI CTCAE) v5 
• 
Change from baseline in targeted vital signs 
• 
Change from baseline in targeted clinical laboratory 
test results 
To determine the maximum tolerable does 
(MTD) and recommended Phase 2 dose 
(RP2D) of DAY101 in combination with 
other therapies.  
• 
Incidence and severity of adverse events, with severity 
determined according to NCI CTCAE v5 
• 
Change from baseline in targeted vital signs 
• 
Change from baseline in targeted clinical laboratory 
test results 
• 
Incidence of dose-limiting toxicities (DLTs) 
SECONDARY OBJECTIVES AND ENDPOINTS IN PHASE 1B 
OBJECTIVE 
ENDPOINTS 
To assess the efficacy of DAY101 in 
combination with other therapies by 
Response Evaluation Criteria in Solid Tumors 
(RECIST) version 1.1 or appropriate tumor 
response criteria. 
• 
ORR as assessed by the proportion of patients with the 
best overall confirmed response of complete response 
(CR) or partial response (PR) according to the 
appropriate tumor response criteria as assessed by 
Investigator 
• 
Duration of response (DOR) in patients with best 
overall response of CR or PR as determined by the 
treating Investigator [from time of first tumor response 
to progression or date of data analysis, whichever 
occurs earlier] 
• 
Duration of progression-free survival (PFS) following 
initiation of study treatment to disease progression, 

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death, or date of analysis, whichever occurs earlier 
according to the appropriate tumor response criteria 
• 
Duration of overall survival (OS) following initiation 
of study treatment to time of death 
• 
Time to response (TTR) in patients with best overall 
response of CR or PR as determined by treating 
Investigator [from initiation of study treatment to date 
of first response] 
• 
Comparing the DOR in patients with CR or PR as 
determine by treating Investigator with the DOR 
observed with the immediate prior line of anticancer 
treatment 
To characterize the pharmacokinetic (PK) 
profile of DAY101 in combination with other 
therapies. 
• 
Plasma concentration of DAY101 at specified time 
points in order to define PK parameters 
To characterize pharmacodynamic (PD) 
effects of DAY101 in combination with other 
therapies. 
• 
PD to be assessed by relevant assay or platform 
including but not limited to RNA sequencing and 
immunohistochemistry (Please see Appendix E).  
EXPLORATORY OBJECTIVES AND ENDPOINTS IN PHASE 1B 
OBJECTIVES 
ENDPOINTS 
To evaluate the genomic profile of archival 
tumor biopsies or fresh tumor biopsies (if 
available) from patients who will be treated 
with DAY101 in combination with other 
therapies.  
• 
Assess genomic alterations from archival tumor biopsy 
or fresh tumor specimens using a relevant platform(s) 
such as, but not limited to, next-generation sequencing 
and circulating tumor DNA (ctDNA) 
To characterize pathway modulation, and/or 
genomic alterations in tumor biopsies. 
To characterize genomic alterations in 
ctDNA. 

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Table 6: 
Phase 2 Study Objectives and Endpoints 
PRIMARY OBJECTIVE AND ENDPOINTS IN PHASE 2 
OBJECTIVE 
ENDPOINTS 
To evaluate the efficacy of DAY101 by 
RECIST version 1.1 or appropriate tumor 
response criteria as a monotherapy, or in 
combination with other therapies. 
• 
Overall response rate (ORR) as assessed by the 
proportion of patients with the best overall confirmed 
response of complete response (CR) or partial response 
(PR) according to the appropriate response assessment 
criteria for the disease setting as assessed by the 
Investigator  
SECONDARY OBJECTIVES AND ENDPOINTS IN PHASE 2 
OBJECTIVE 
ENDPOINTS 
To assess the safety and tolerability of 
DAY101 as monotherapy, or in combination 
with other therapies. 
• 
Incidence and severity of adverse events, with severity 
determined according to NCI CTCAE v5 
• 
Change from baseline in targeted vital signs 
• 
Change from baseline in targeted clinical laboratory 
test result 
To assess additional efficacy parameters of 
DAY101 as monotherapy or in combination 
with other therapies. 
• 
DOR in patients with best overall response of CR or 
PR as determined by the treating Investigator [from 
time of first tumor response to progression or death, 
whichever occurs earlier] 
• 
Duration of progression-free survival (PFS) following 
initiation of study treatment to disease progression or 
death, whichever occurs earlier according to the 
appropriate tumor response criteria 
• 
Duration of OS following initiation of study treatment 
to time of death 
To characterize the tumor responses observed 
with DAY101 as monotherapy or in 
combination with other targeted therapies. 
• 
 Time to response (TTR) in patients with best overall 
response of CR or PR as determined by treating 
Investigator [from initiation of study treatment to date 
of first response] 
To characterize the pharmacokinetic (PK) 
profile of DAY101 in combination with other 
therapies. 
• 
Plasma concentration of DAY101 at specified time 
points in order to define PK parameters 
To characterize pharmacodynamic (PD) 
effects of DAY101 in combination with other 
therapies. 
• 
PD to be assessed by relevant assay or platform 
including but not limited to RNA sequencing and 
immunohistochemistry (Please see Appendix E).  
 
To determine the relationship between PK 
and PD of DAY101 in combination with 
other therapies.  
• 
Determine the relationship between PK and PD 
biomarkers 

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3. 
INVESTIGATIONAL PLAN 
3.1. 
Study Design 
This is a Phase 1b/2, multi-center, open-label, umbrella study of patients ≥ 12 years of age 
with recurrent or progressive solid tumors with alterations in the key proteins of the 
RAS/RAF/MEK/ERK pathway, which will be referred to as the MAPK pathway. Patients 
with these alterations will be identified through molecular assays as routinely performed at 
Clinical Laboratory Improvement Amendments of 1988 (CLIA) or other similarly certified 
laboratories. 
Based on the identified alterations in the key proteins of the MAPK pathway, patients may be 
offered the opportunity to participate in one or more sub-protocols within this umbrella study 
of DAY101 as monotherapy or in combination with other therapies. Enrollment will be based 
on the specific eligibility criteria described in each sub-protocol. 
Study DAY101-102 (master study) and sub-protocols consist of a screening period, a 
treatment period, a safety follow-up period, and a long-term follow-up (LTFU) period where 
survival status, and subsequent anticancer therapies will be collected. 
DAY101 will be administered as specified in the sub-protocol. Additional dose schedules 
may be explored. Dose level(s), dose schedule(s), and cycle lengths for DAY101 as 
monotherapy or in combination with other therapies will be specified in each sub-protocol. 
Cycles will repeat, as specified in each sub-protocol, until disease progression, unacceptable 
toxicity, withdrawal of consent, or death. 
Patients will undergo radiographic evaluation of their disease at baseline, at the end of 
 
 for 1 year and then
thereafter, or as specified in a given sub-protocol. 
Generally, response assessment will be performed according to Response Evaluation Criteria 
in Solid Tumors (RECIST) version 1.1 for solid tumors. Alternative criteria may be used in 
specific disease settings, such as glioma, where response assessment will be assessed by 
RANO criteria. Appropriate response criteria for tumors are described in Appendix B and 
Appendix C. 
Patients who have radiographic evidence of disease progression may be allowed to continue 
DAY101 (and combination partner if applicable) if, in the opinion of the Investigator, the 
patient is deriving clinical benefit from continuing study treatment, and continuation of 
treatment is approved by the Sponsor. 
DAY101 for oral dosing is provided a white to off-white
powder as an immediate-
release 100 mg tablet. The 100 mg tablets are red to yellowish-red oval tablets. All products 
are labeled DAY101. 
Other therapies may be included in future sub-protocols and will be further specified within 
each sub-protocol. 
Scheduled activities will be performed in as outlined in the Schedule of Activities within 
each sub-protocol. The study design schema is shown in Figure 3. Refer to the relevant sub-
protocol for each sub-protocol design schema. 

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Figure 3: 
Study Design Schema 
3.1.1. 
End of Study and Length of Study 
For details related to end of study and length of study, please see relevant sub-protocols. 
3.1.2. 
Number of Patients 
Maximum number of patients enrolled will be dependent on the sub-studies included. Please 
refer to specific sub-protocol for more detail. 
3.2. 
Investigational Sites 
Refer to the sub-protocols for the number of institutions participating in this study. 

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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.  Inclusion and exclusion criteria can be found within each sub-protocol. 

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5. 
TREATMENT 
5.1. 
Investigational Product 
DAY101 for oral dosing is a white to off-white
powder formulated as a 100 mg 
immediate-release tablet. The 100 mg tablets are red to yellowish-red oval tablets. All 
products are labeled DAY101. 
The site pharmacist will dispense the tablets to the patient, 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 30°C) 
and protected from light. Additional details regarding the investigational product are 
provided in the DAY101 IB. 
Additional therapies may be included. For further details, please see relevant sub-protocols. 
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 
must not be cut or crushed.  
If the patient vomits the tablets and they are still recognizable, then the patient can be re-
dosed. 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 re-dosed. 
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. The study drug 
administration diary will also be assessed at each clinic visit. 
For additional dosing administration instruction for each sub-protocol, please refer to 
individual sub-protocol for details. 
5.2.2. 
Dose-Limiting Toxicity 
Assessment of DLT will be further specified in relevant sub-protocols. 
5.2.3. 
Dose Modifications 
Please refer to the sub-protocols for study drug modifications and reduction details. 
5.2.4. 
Management of Treatment-Related Events 
Please refer to the sub-protocols for study drug modifications and treatment-related events 
management guidelines for DAY101 and/or combination partners. 

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5.3. 
Removal of Patients from Therapy or Assessment 
Patients may withdraw from the study at any time. Patients who withdraw from therapy and 
do not withdraw consent will be referred to as “discontinue study treatment” and will be 
followed for LTFU. Over the course of the study, a patient may discontinue from study 
treatment for any of the reasons listed below: 
• Disease progression as assessed by the Investigator, except if, in the opinion of 
the Investigator and with permission of the Sponsor, the patient is deriving 
clinical benefit from continued study treatment 
• Unacceptable toxicity 
• Intercurrent illness compromising the ability to fulfill protocol requirements 
• Dosing interruption > 28 days, unless resumption of treatment approved by the 
Sponsor 
• Requirement for alternative treatment in the opinion of the Investigator 
• Significant noncompliance to protocol 
• Pregnancy 
• Withdrawal of consent or assent by the patient or the patient’s parent or legal 
guardian 
• Loss to follow-up 
• Death 
When a patient discontinues from treatment, the patient will undergo the end of treatment 
(EOT) visit, as outlined in Section 6.24 . 
5.4. 
Prior and Concomitant Medications 
5.4.1. 
General 
All medications that were used from 28 days prior to enrollment through 30 days following 
the last dose of study drug will be recorded in the 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. Please refer to the sub-protocols for eligibility criteria and specific 
concomitant mediation information.  
5.4.2. 
Allowed Concomitant Medications 
Please refer to the sub-protocols for specific allowed concomitant medications.  
5.4.3. 
Prohibited Concomitant Medications 
Please refer to the sub-protocols for specific prohibited concomitant medications.  

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5.4.4. 
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. 
Please see each sub-protocol for instruction on holding DAY101 and other investigational 
drugs. 
5.4.5. 
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. Therapy should be held for 6 days before surgical 
intervention. Patients undergoing surgical intervention are permitted to restart study 
treatment 6 days following surgical intervention after discussion with and approval by the 
Sponsor. The surgical intervention should be recorded on the appropriate electronic case 
report form (eCRF). For patients requiring surgical intervention due to clinical or 
radiographic evidence of tumor progression, patients should be withdrawn from study. 
5.5. 
Preparation, Handling, Storage and Accountability 
1. The Investigator or designee must confirm that appropriate temperature conditions 
have been maintained during transit for all study drug(s) received and that any 
discrepancies are reported and resolved before use. 
2. Only participants enrolled in the study may receive study drug(s) and only trained site 
staff may supply or administer study treatments.  
3. The Investigator, institution, or head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance 
(i.e., receipt, reconciliation, and final disposition records). 
4. Further guidance and information for the final disposition of unused study drug(s) 
tablets are provided in the Pharmacy Manual. 

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6. 
TESTS AND EVALUATIONS 
All required observations and schedules are described in more detail in Sections 6.1 through 
6.27. 
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 specified in the sub-protocol. 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 
 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. 
Screening tests that are completed in the 48 hours prior to start of DAY101 and duplicate 
tests according to the Schedule of Activities (see subprotocol(s) for specific 
schedule(s) of assessments) will be accepted as fulfilling the
 assessments. 
Repeat testing on
is not necessary for this scenario, and results should be 
recorded in the screening set of eCRFs. 
A completed screening form and supportive materials will be sent to the Sponsor or designee 
when a potential study candidate is identified. Any reports (e.g., pathology report, MRI 
report) supportive to the screening 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 Sponsor. A 
revised screening form should be submitted to the Sponsor or its designee for rescreened 
patients. See the Study Binder for enrollment form, patient number assignment, contact 
numbers, and other details of enrollment. 
The approved screening 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 Activities (see 
subprotocol(s) for specific schedule(s) of assessments). Patients who meet the eligibility 

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criteria, as outlined in each sub-protocol, will be enrolled in this study. Procedure details, 
timing and details regarding assessments can be found in the Schedule of Activities in each 
relevant sub-protocol. 
6.3. 
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. 
6.4. 
Archival Tumor Samples 
See each sub-protocol.  
6.5. 
Freshly Acquired Tumor Samples for Pharmacodynamic Analysis 
See each sub-protocol.  
6.6. 
 Circulating Tumor DNA (ctDNA) Samples: Blood 
For circulating tumor DNA (ctDNA) sample collection regimen and schedule, please refer to 
sub-protocols. 
6.7. 
Physical Examination 
Physical examinations will also include review of systems (neurological, chest, extremities, 
genitourinary, head/ears/eyes/nose/throat, lymph nodes, musculoskeletal, pulmonary, and 
skin) during screening, prior to the start of each new cycle, at EOT, and at safety follow-up. 
Symptom-directed physical examination, including measurement of weight and height, may 
be performed at other time points after screening per the Scheduled of Activities in each sub-
protocol.  
Patient’s skin discomfort, visual disturbance, and cardiopulmonary symptoms need to be 
noted during physical examination. If any abnormalities arise, relevant specialist 
examinations should be performed in a timely manner. 
6.8. 
Eastern Cooperative Oncology Group Status/Lansky 
Performance Status 
The Eastern Cooperative Oncology Group (ECOG) (patients aged 16 years or older) or 
Lansky (patients aged less than 16 years) Status should be assessed in all patients per the 
Schedule of Activities in each sub-protocol (See Appendix A). 
6.9. 
Assessment of Change in Pubertal Development (Tanner Stage) 
For patients 12 to < 18 years of age, pubertal stage will be measured according to the Tanner 
Stages before the start of treatment (screening) and yearly thereafter while on active 
treatment through sexual maturity (Marshall and Tanner 1969, Marshall and Tanner 1970). 
For female patients, age at menarche will be recorded. 

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6.10. 
Vital Signs 
Vital signs should include the following: 
• Systolic and diastolic blood pressure (BP) (For more information on normal 
ranges of BP by height and weight refer to Appendix H) 
• Heart rate, respiratory rate, oxygen saturation, body temperature  
For patients, < 18 years of age, blood pressure should be taken manually (auscultatory 
method) using an appropriate-sized cuff for the patient’s arm dimension with feet on the 
floor. Care should be taken to measure blood pressure prior to other assessments and once 
child has been calm for a sufficient amount of time. Abnormal blood pressures should be 
repeated. If (automated) oscillometric methods must be used, then abnormal values should be 
confirmed with a manual measurement. 
6.11. 
Ophthalmology Examination  
See Sub-Protocol DAY101-102a and Sub-Protocol 102b. 
6.12. 
Visual Symptom Assessment 
See Sub-Protocol DAY101-102a and Sub-Protocol 102b. 
6.13. 
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). 
Subsequent examinations should be symptom-directed and as clinically indicated and 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. Any new 
or worsening skin lesions or rashes should be reported as adverse events.  
Melanoma patients with clinical lesions followed for response please refer to Appendix B for 
additional details.  
Recommended prophylactic skin care regimen and management options for rashes is 
available in each sub-protocol. It is recommended all patients receiving study drug follow the 
prophylactic skin care regimen. 

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6.14. 
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. 
6.15. 
Height and Bone Age 
Patients 12 – 18 years (inclusive) should have changes in height compared to standard 
growth curves to monitor potential effects on bone growth. 
Patients 12 – 18 years (inclusive) will have a bone age assessment via bone age radiograph 
of the left wrist during screening. Patients without epiphyseal closure at the time of screening 
will have a bone age left wrist radiograph performed every 6 months to monitor for the 
potential risk of growth retardation. 
6.16. 
Cardiac Function 
6.16.1. 
Electrocardiograms 
Twelve-lead resting electrocardiogram (ECGs) will be performed in triplicate per the 
Schedule of Activities in each sub-protocol. To minimize variability, it is important that 
patients be in a resting position for at least 5 minutes prior to each ECG evaluation. 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. Any 
clinically significant changes in ECGs that occur during the study should be reported as AEs 
in the eCRF. 
6.16.2. 
Echocardiogram/Multiple-Gated Acquisition 
Echocardiogram (ECHO) or multi-gated acquisition (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. 
6.17. 
Laboratory Tests 
For pediatric/adolescent patients (aged < 18 years), blood volumes drawn will be minimized, 
in accordance with the European Commission (EC)’s recommendations, “Ethical 
considerations for clinical trials on medicinal products conducted with the pediatric 
population” (2008) and “Ethical considerations for clinical trials on medicinal products 
conducted with minors” (2017). 
Routine laboratory tests 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.  

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6.17.1. 
Pregnancy Test 
Urine or serum pregnancy tests are required for women of childbearing potential (surgically 
sterilized female patients or those who have not experienced menses for at least 2 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. 
6.17.2. 
Hematology 
Hematology should include assessment of the following: hemoglobin, hematocrit, red blood 
cell count, white blood cell count with differential, and platelet count. 
6.17.3. 
Serum Chemistries 
Serum chemistries (non-fasting) should include assessment of the following: alkaline 
phosphatase, albumin, alanine aminotransferase (ALT), AST, CPK, blood urea nitrogen 
(BUN), creatinine, creatinine clearance, glucose, lactate dehydrogenase, total and direct 
bilirubin, total protein, sodium, serum calcium (corrected calcium), phosphate, magnesium, 
and potassium. For calculated creatinine clearance, see Appendix I. 
6.17.4. 
Coagulation Panel 
Serum coagulation panel should include assessment of the following: prothrombin time 
(PT)/international normalized ratio (INR) and activated prothrombin time (PTT). 
6.17.5. 
Thyroid Function Tests 
Thyroid function tests should include assessment of the following: thyroid stimulating 
hormone (TSH) and free tetraiodothyronine (free T4). Triiodothyronine (T3) may be 
obtained as a reflexive test if considered necessary by the Investigator based on local 
practice.  
6.18. 
Pharmacokinetic Samples: Blood 
For PK sample collection regimen and schedule, please refer to sub-protocols. 
6.19. 
Disease Assessment 
6.19.1. 
Tumor Measurements 
Disease assessment must be conducted in accordance with the Imaging Manual. Tumors will 
be assessed by radiographic tumor measurements using computed tomography (CT) and/or 
MRI (as indicated). 
CT/MRI must be performed within 28 days prior to the first dose of study drug during 
screening. To ensure image consistency, the same imaging modalities and acquisition 
protocols used at screening are to be used for subsequent tumor assessments. 
Investigators must conform to the CT and/or MRI acquisition requirements specified in the 
Imaging Manual consistently for all patients throughout the study. Disease assessments will 

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use RECIST version 1.1 or RANO criteria, as clinically appropriate (see Appendix B and 
Appendix C). 
6.19.1.1. 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. 
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. 
6.20. 
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. The patient or the patient’s 
parent/legal guardian should be contacted regularly to assess AE status. 
6.21. 
Survival Status 
Patients will be followed for survival status, date of progression, and subsequent anticancer 
therapies by telephone or any other method. 
6.22. 
Study Drug Administration and Dosing Diary 
Completion of the outpatient dosing diary will include recording of study drug dosing. 
6.23. 
Concomitant Medication 
All medications that were used from 28 days prior to enrollment through 30 days following 
the last dose of study drug will be recorded in the eCRF. 
6.24. 
End of Treatment Visit 
EOT is defined as Day 28 (± 7 days) of the final cycle of treatment (or time of premature 
discontinuation of treatment). The EOT assessments and procedures will be conducted in 
accordance with the Schedule of Activities in the relevant sub-protocol. 
6.25. 
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. 

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6.26. 
Long-Term Follow-up 
After study treatment discontinuation, LTFU assessments will occur approximately every 3 
months (± 1 month) until the patient withdraws consent for further participation, is lost to 
follow-up, has died, or the study is closed. For any patient who discontinues study treatment 
prior to disease progression, tumor assessment will progress accordingly as if on study 
treatment and will be requested to return to site for continued monitoring and assessment. 
After progression and in LTFU, 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. LTFU may be conducted by telephone except for those patients who have not 
yet progressed after treatment discontinuation. 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. The first 
LTFU assessment will occur 3 months (± 1 month) after the EOT visit. 
6.27. 
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 
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. 

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7. 
PLANNED ANALYSES 
A statistical analysis plan (SAP) will be prepared and finalized prior to database lock for 
each sub-protocol. This document will provide further details regarding the definition of 
analysis variables and analysis methodology to address all study objectives. Any deviations 
in the planned analysis as stated in the protocol will be delineated in the SAP. Any deviations 
from the SAP will be reported in the clinical study report. 
7.1. 
Analysis Populations 
The populations for analysis are defined in Table 7. 
Table 7: 
Population Definitions 
Population 
Description 
Efficacy 
All patients who received at least 1 dose of study drug and have 
measurable disease as determined by the Investigator at baseline and 
have at least 1 follow-up imaging or radiographically confirmed 
progressive disease prior to the first imaging timepoint (FAS) 
Safety 
 
 
DLT 
 
All patients enrolled in the study who received at least 1 dose of 
study treatment (SAS) 
 
Patients enrolled in a safety run-in cohort, received at least 1 dose of 
study treatment, and completed 75% of dosing in Cycle 1, unless 
discontinued for toxicity 
Abbreviations: DLT, dose-limiting toxicity; FAS, Full Analysis Set; SAS, Safety Analysis Set. 
7.2. 
Determination of Sample Size 
For methods related to determination of sample size, refer to specific sub-protocols. 
Additional patients will be enrolled to account for any patients who are lost to follow-up or 
have no follow-up imaging. 
7.3. 
Statistical Methods 
The SAP will be produced individually for each sub-protocol prior to analysis. 
7.3.1. 
Efficacy Analyses 
The efficacy analyses will be performed on the full analysis set (FAS) population which 
includes all patients who received at least 1 dose of study drug and have measurable disease 
as determined by the Investigator at baseline and have at least 1 follow-up imaging or 
radiographically confirmed progressive disease prior to the first imaging timepoint. 
ORR as assessed by the proportion of patients with the best overall confirmed response of 
CR or PR, according to the appropriate tumor response criteria as assessed by Investigator 
will be calculated and an exact CI will be calculated. DOR in patients with best overall 
response of CR or PR as determined by the treating Investigator defined as from time of first 
tumor response to progression or date of data analysis, whichever occurs earlier will be 
calculated. PFS is defined as the time from the date of the first dose of study drugs to the first 
occurrence of disease progression according to the appropriate tumor response criteria as 

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assessed by Investigator, or death from any cause, whichever occurs earlier. OS is defined as 
the period from the date of the first dose of study drugs until the date of death from any 
cause. Kaplan-Meier curves will be plotted for DOR, PFS, and OS. TTR in patients with best 
overall response of CR or PR will be determined by the treating Investigator from the 
initiation of study treatment to the date of first response. The timepoint for the analysis of 
response for Phase 2 studies’ primary efficacy objective will be when all patients have a 
minimum of 6 months of follow-up.  
7.3.2. 
Safety Analyses 
Safety will be assessed by clinical review of all relevant parameters, including AEs, SAEs, 
AESIs, laboratory values, and vital signs. Unless specified otherwise, the safety analyses will 
be conducted for the Safety Analysis Set defined in Section 7.1. 
The reported AE term will be assigned a standardized Preferred Term using the Medical 
Dictionary for Regulatory Activities (MedDRA), version 24.0 or later, and adverse event 
severity will be graded according to National Cancer Institute (NCI) CTCAE v5.0. 
Treatment-emergent adverse events will be tabulated according to MedDRA by system organ 
class, high level terms, and preferred terms and will be include the following categories: 
frequency of AEs overall, by grade, relationship to study treatment, time-of-onset, duration 
of the event, duration of resolution, and any concomitant medications administered. A listing 
of TEAEs resulting in study drug discontinuation will be provided. For reporting purpose, 
treatment-emergent adverse event is defined as new or worsening adverse events occurring 
on or after the first dose of study drug is administered until the clinical cutoff date. All safety 
analyses of adverse events will also include all adverse events with onset on or after the first 
study drug treatment until the data cutoff date.  
7.3.2.1. 
Deaths 
All deaths on study should be reported and recorded. 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 post-baseline 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. Descriptive statistics for the actual 
values of clinical laboratory parameters (and/or change from baseline in clinical laboratory 
parameters) and other safety parameters as deemed appropriate will be presented for all 
scheduled measurements over time. Mean laboratory values over time will be presented for 
key laboratory parameters. 

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7.3.2.3. 
Vital Signs 
All patients will have pretreatment baseline vital signs and pre-dose measurements as 
described in the Schedule of Activities in the relevant sub-protocol. 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 post-baseline value will be 
determined relative to the baseline vital sign measurements only. 
7.3.2.4. 
Concomitant Medications 
Prior and concomitant medications will be coded to the generic term using the current 
version of the World Health Organization (WHO) Drug Dictionary and listed by patient. 
7.3.3. 
Pharmacokinetic Analyses 
Plasma concentrations of DAY101 and other therapies (as applicable based on sub-protocol) 
will be determined with  validated bioanalytical methods. Plasma concentrations will be 
analyzed at specified time points in order to generate PK parameters as appropriate and will 
be described in more detail in the sub-protocol(s). Summary statistics will be generated as 
appropriate. 

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8. 
ADVERSE EVENTS 
8.1. 
Adverse Events, Adverse Events of Special Interest, and Serious 
Adverse Events 
Adverse events will be reported by the patient (or, when appropriate, by a caregiver, 
surrogate, or the patient’s legally authorized representative). 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE, AESI, or SAE and remain responsible for 
following up AEs that are serious, considered events of special interest, considered related to 
the study intervention or study procedures, or caused the patient to discontinue DAY101 or 
combination partner. 
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 G for instructions on collection, assessing, and reporting of AEs. 
8.1.1. 
Time Period and Frequency for Collecting Adverse Event, Adverse Events of 
Special Interest, and Serious Adverse Event Information 
Report all SAEs deemed related to protocol-mandated procedures from the signing of 
informed consent through to start of treatment with DAY101 or combination partner, 
whichever is administered first. 
Report all AEs, AESIs, including SAEs, from the start of treatment until 30 days after the last 
dose of DAY101 or combination partner, whichever was administered last. 
For patients who screen fail or are enrolled but do not receive study drug, the reporting 
period for SAEs ends 30 days after the last procedure (e.g., screening procedure). 
Table 8: 
Summary of AE Collection Periods 
Time Period 
AE Collection 
ICF signature to start of study drug 
Protocol/procedure-related SAEs only 
Start of study drug to 30 days after last 
study drug dose (DAY101, additional study 
treatment, whichever was administered 
last)a 
All AEs, AESIs, and SAEs 
Beyond 30 days after last study drug dose 
(DAY101, additional study treatment, 
whichever was administered last) 
Any SAEs or AESIs related to study drug  
Abbreviations: AE, adverse event; AESI, adverse event of special interest; ICF, informed consent form; 
SAE, serious adverse event. 
a See Section 8.1.3 for follow-up of AEs. If a patient begins a new anticancer therapy, the AE reporting 
period for non-SAEs and SAE/AESIs not related to study drug ends at the time the new treatment is started. 
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 G. The Investigator will 
submit any updated SAE data to the Sponsor within 24 hours of their being available.  

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Non-serious AESIs should be reported in the same manner as reporting of SAEs. In addition, 
for both serious and non-serious AESIs, the appropriate targeted questionnaires should be 
submitted to the Sponsor with the SAE report or as soon as possible. 
If the Investigator learns of any SAE and/or AESI, 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, Adverse Events of Special Interests, 
and Serious Adverse Events 
The method of recording, evaluating, and assessing causality of AEs, AESIs, and SAEs and 
the procedures for completing and transmitting SAE and non-serious AESI reports are 
provided in Appendix G. 
Care will be taken not to introduce bias when detecting AEs, AESIs, 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, Adverse Events of Special Interests, 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 G. 
Non-serious AESIs should be followed-up in the same manner as SAEs. 
If a patient begins a new anticancer therapy prior to 30 days post study drug EOT, the AE 
reporting period for non‑SAEs and SAE/AESIs not related to study drug ends at the time the 
new treatment is started. 
8.1.4. 
Regulatory Reporting Requirements for Any SAEs and Non-Serious AESIs 
Occurring During this Study Must Be Reported as Follows: 
• Prompt notification of an SAE or AESI by the Investigator to the Sponsor is 
essential so that legal obligations and ethical responsibilities toward the safety of 
patients and the safety of a study intervention under clinical investigation are met. 
Any SAEs (including Serious AESIs) must be reported to the Sponsor via email at 
 within 24 hours.  Non-serious AESI’s should be 
reported using the same processes and timelines as SAEs. 
• 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 countryspecific regulatory 
requirements relating to safety reporting to the regulatory authority, Institutional 
Review Boards (IRB)/Independent Ethics Committees (IEC), and Investigators. 

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• 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. A non-serious AESI does not 
require expedited reporting to any regulatory health authority or agency. 
8.1.5. 
Pregnancy or Combination Partner 
There is no relevant clinical experience with DAY101 (as a single agent or in combination) 
in pregnant or lactating female patients, and animal reproductive studies have not been 
performed. Women 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. 
• 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 6 months after completing DAY101. 
• 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 F. 
• 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 F. 
• Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
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 6 months for female patients and for 6 months for female partners of 
male patients. 
8.1.6. 
Death Events 
Deaths occurring during the AE reporting period, regardless of attribution to DAY101 or 
combination partner will be recorded as a serious AE and expeditiously reported to the 
Sponsor. This includes death attributed to the progression of malignant disease. 
When recording a death, the event or condition that caused or contributed to the fatal 
outcome should be recorded as the single medical condition on the Adverse Event eCRF and 
SAE report form, as applicable. If the cause of death is unknown and cannot be ascertained at 
the time or reporting, then “unexplained death” should be recorded on the Adverse Event 
eCRF and SAE reporting form, as applicable. 

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8.2. 
Data Monitoring Committee (DMC) 
An independent Data Monitoring Committee (DMC) will be established to oversee the safety 
aspects of the study and to render dose safety decisions as applicable based on sub-protocol 
(see Section 8.2.1). 
8.2.1. 
Risk Management 
An independent DMC will also be commissioned to monitor data on an ongoing basis to 
ensure the continuing safety of the subjects enrolled in the study and to review available 
efficacy data. The independent DMC will be composed of experts in the field of oncology, as 
well as biostatistics, and clinical trial conduct. Members of the independent DMC will not be 
associated with the conduct of the study, except in their role on the independent DMC. The 
Sponsor will also designate an independent biostatistical team not affiliated with the project 
to prepare and provide study data to the independent DMC. The independent DMC will meet 
periodically to review ongoing efficacy and safety data. Timing of the first independent 
DMC meeting will be enrollment driven, and subsequent meetings will occur approximately 
every 3 months (or longer based on patient accrual) to review safety across the DAY101-102 
master study and sub-protocols.  Complete details regarding the composition and governance 
of the independent DMC, independent DMC responsibilities, authorities, and procedures will 
be outlined in a separate independent DMC Charter. The independent DMC responsibilities, 
authorities, and procedures will be documented in a separate charter. 
8.2.2 
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 DMC accordingly. 
Serious adverse events will be reported within 24 hours to the Sponsor’s safety team by 
email and be subject to a second assessment by the Sponsor’s safety physician. 
8.3. 
Stopping Rules 
AEs and SAEs are expected to occur frequently in this study, based on the patient population 
being accrued and on the nature of the advanced malignancies under study. SAEs will serve 
as the basis for pausing or prematurely stopping the study. Unexpected SAEs that are 
assessed as related to DAY101 or combination partner will continuously be reviewed to 
determine any necessary pausing or stopping of the study. The study may be paused for 
enrollment if any patient experiences any of the following events:  
• Life-threatening (Grade 4) toxicity attributable to DAY101 or combination 
partner that is unexpected and unmanageable (i.e., does not resolve to Grade 3 or 
lower within 7 days)  
• Death related to DAY101 or combination partner 
Review of these SAEs, and any decision to pause enrollment or terminate the study, will be 
determined by the Sponsor  or at the recommendation of the DMC. Decisions to pause 
enrollment or terminate the study will be communicated promptly to Investigators, 

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IRBs/IECs, Institutional Biosafety Committees (if applicable), and appropriate regulatory 
authorities. 
During any temporary enrollment hold, no new participants can be enrolled, nor can any 
newly enrolled participants start study intervention. Participants who have already started 
study intervention may continue treatment only if the benefit/risk assessment for the 
participant is judged to be positive by the Investigator in consultation with the Sponsor. 
8.4. 
Grading and Intensity of Adverse Events 
The Investigator will grade the severity of each AE using, when applicable, the NCI CTCAE, 
version 5. 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 
below. 
Table 9: 
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. 

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8.5. 
Relationship to Study Drug 
The Investigator is required to assess the causality/relationship between each AE and the 
study drug as not related or related and record the assessment on the source documents and in 
the CRF AE page. Medical judgment should be used to determine the likely relationship of 
the AE to the study drug considering all relevant factors including (but not limited to) 
relevant history, concomitant medical condition, and concomitant medications. 
Determination should be based on assessment of temporal relationships, biologic plausibility, 
association (or lack of association) with underlying disease, and presence (or absence) of a 
more likely cause. 
• Related: A causal relationship between medicinal product and an AE is at least a 
reasonable possibility. The AE cannot reasonably be explained by the patient’s 
clinical state, concomitant medical condition or concomitant therapies, and a 
temporal relationship exists between the event onset and administration of the 
study drug. 
• Not Related: It is plausible that the AE has an etiology other than the study drug 
(e.g., preexisting condition, underlying disease, concomitant medical condition, or 
concomitant medication). 
8.6. 
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. 
For non-serious AESIs reported to the Sponsor, the Investigator should submit the 
appropriate follow-up reports regarding the patient’s subsequent course similar to what is 
required for SAE follow-up.  

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9. 
STUDY ADMINISTRATION 
9.1. 
Regulatory and Ethical Considerations 
9.1.1. 
Regulatory Authority Approval 
This study will be conducted in accordance with the standard of Good Clinical Practices 
(GCP), 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. 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 
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 
regards 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, 

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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 International Council for Harmonisation (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 
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, 

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incorrect, and/or inconsistent data have been accounted for. Additional instructions on eCRF 
completion are provided in the electronic data capture (EDC) manual.  
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: 
• Checking and assessing the progress of the study 
• Reviewing study data collected to date for completeness and accuracy 
• Conducting source document verifications by reviewing each patient’s eCRF 
against source documents 
• Identifying any issues and addressing resolutions 
• Recording and reporting protocol deviations not previously reported to the 
Sponsor 
• Confirming that SAEs and non-serious AESIs have been properly reported to the 
Sponsor and submitted to the IRB/REB/IEC/HREC if appropriate 
These activities will be done 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: 
• Submission of all study data to the Sponsor 
• Completion of all data clarifications and/or resolutions 
• Reconciliation and final disposition of investigational product 
• 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. 

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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 2 years after the last marketing 
application approval or 2 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: 
Eastern Cooperative Oncology Group (ECOG) Performance Status 
and Lansky Performance Score 
Table 10: 
ECOG Performance Status 
ECOG Performance Statusa 
Grade 
ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry 
out work of a light or sedentary nature, e.g., light housework, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work 
activities. Up and about more than 50% of waking hours 
3 
Capable of only limited selfcare, confirmed to bed or chair more than 50% of 
waking hours 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or 
chair 
5 
Dead 
aAs published in Am. J. Clin. Oncol. (Oken et al., 1982) 
Table 11: 
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 B: 
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, Table 12). Notable changes are highlighted below: 
• Number of lesions required to assess tumor burden for response determination has 
been reduced from a maximum of 10 to a maximum of 5 total (and from 5 to 2 per 
organ, maximum). 
• 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. 
• 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: 
• 10 mm by CT scan (CT scan slice thickness no greater than 5 mm) and 20mm by 
chest X-ray 
• 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 ≥ 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: 
• 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. 
• ‘Cystic lesions’ thought to represent cystic metastases can be considered as 
measurable lesions, if they meet the definition of measurability described above. 
• 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. 

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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 
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 ≥10mm 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 ≤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 5 lesions total (and a maximum of 2 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’. 

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Evaluation of Target Lesions 
• 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. 
• PR: At least a 30% decrease in the sum of diameters of target lesions, taking as 
reference the baseline sum diameters. 
• 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). 
• 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. 
• 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). 
• Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or 
maintenance of tumor marker level above the normal limits. 
• 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 best overall response 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 12. 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 4 weeks later). Guidance on the determination of 
best overall confirmed response is provided in Table 13. 
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 12: 
Overall Assessment by RECIST 1.1 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 NE or none at 
BL 
No 
PR 
SD 
Non-PD or NE 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 13: 
Best Overall Assessment by RECIST 1.1 
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 
Abbreviations: 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. 

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Appendix C: 
Response Assessment in Neuro-Oncology (RANO) Criteria for 
Primary CNS Malignancies 
The RANO criteria (Wen et al. 2017; Table 14) 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 14: 
RANO Response Criteria Incorporating MRI and Clinical Factor 
RESPONSE CATEGORY 
CRITERIA 
Complete Response 
• 
Disappearance of all measurable and non-measurable enhancing 
disease 
• 
Stable or improved nonenhancing FLAIR/T2 lesions 
• 
No new lesions 
• 
Clinically stable or improved with no reliance on corticosteroids 
(except for physiological replacement) 
Partial Response 
• 
≥ 50% decrease from baseline of all measurable enhancing lesions 
• 
No progression of non-measurable disease 
• 
Stable or improved nonenhancing FLAIR/T2 lesions 
• 
No new lesions 
• 
Clinically stable or improved, with stable or reduced corticosteroids 
compared to baseline 
Progressive Disease 
• 
≥ 25% increase from baseline in enhancing lesions despite stable or 
increasing steroid dose 
• 
Significant increase in nonenhancing FLAIR/T2 lesions not 
attributable to other non-tumor causes 
• 
Any new lesions 
• 
Clinical deterioration no attributable to other non-tumor causes and 
not due to steroid decrease 
Stable Disease 
• 
Does not meet other criteria for response or progression 
• 
Stable nonenhancing FLAIR/T2 lesions 
• 
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. 

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A measurable lesion is evaluated by contrast-enhancing MRI and: 
• Has clearly defined margins 
• Is visible on 2 or more axial slices, preferably < 5 mm thick 
• Is at least 10 mm in size if slice thickness is < 5 mm (or 2× slice thickness if > 
5 mm) 
• Does not measure a cystic cavity 
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 2 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 1 or 2 are 
increasing in size, the enlarging lesions should be considered the measurable lesions for 
evaluation of response. 

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Appendix D: 
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 
genetic and molecular analysis and cell line development. 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. 
For a comprehensive list of research use of tissue and clinical data, see Appendix E. 
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 cell lines, 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 test 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 E: 
List of Research Uses of Tissue, Plasma and Clinical Data 

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Appendix F: 
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: 
• Premenarchal 
• 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: 
Male patients are not allowed to donate sperm during the course of this study or within 
180 days after receiving their last dose of study drug.  
Female and male patient of reproductive potential must agree to avoid becoming pregnant or 
impregnating a partner, respectively, while receiving study drug(s) and for 180 days after the 
last dose of study drug(s) by complying with  one of the following:  
(1) practice abstinence† from heterosexual activity; 
OR 
(2) use two acceptable methods of contraception in which one method must be a 
barrier (a condom is preferred) in addition to one of the highly effective contraception 
methods described below during heterosexual activity. 
Acceptable methods of highly effective contraception methods with a failure rate of less than 
1% per year are‡: 
• Combined estrogen- and progestogen-containing hormonal contraception 
associated with inhibition of ovulation given PO, intravaginally, or transdermally 
• Progestin-only hormonal contraception associated with inhibition of ovulation 
given PO, by injection, or by implant 

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• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion or ligation 
• Vasectomized partner 
† 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 contraceptive method listed above is restricted by local regulations/guidelines, then it 
does not quality as an acceptable method of contraception for subjects participating at sites in 
this country/region. 
Collection of Pregnancy Information 
Male Patients With Partners Who Become Pregnant 
• 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. 
• 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 6 
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 
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. 
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 6 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. 
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. 

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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. 
Any poststudy 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. 
Any female patient who becomes pregnant while participating in the study will discontinue 
study intervention. 

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• In general, hospitalization signifies that the patient has been detained (usually involving at least 
an overnight stay) at the hospital or emergency ward for observation and/or treatment that would 
not have been appropriate in the physician’s office or outpatient setting. Complications that occur 
during hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other 
serious criteria, the event is serious. When in doubt as to whether hospitalization occurred or was 
necessary, the AE should be considered serious. 
• Events that require an escalation of care when the patient is already hospitalized should be 
recorded as an SAE. Examples of such events include movement from routine care in the hospital 
to the intensive care unit or if that event resulted in a prolongation of the existing planned 
hospitalization. 
• Hospitalization for conditioning chemotherapy, infusion, and monitoring as required by the 
protocol and elective treatment of a preexisting condition that did not worsen from baseline is not 
considered an AE. 
• Planned admissions to hospital for administration of DAY101/additional therapies or other 
protocol-mandated procedures do not qualify as serious unless a new AE occurs that results in 
prolongation or meets any of the other “serious” criteria. 
d. 
Results in persistent disability/incapacity 
• The term “disability” means a substantial disruption of a person’s ability to conduct normal life 
functions. 
• This definition is not intended to include experiences of relatively minor medical significance, 
such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle) that may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
f. 
Other situations: 
• Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the patient or may require 
medical or surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious. 
• Examples of such events include invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias, or convulsions that do 
not result in hospitalization, or development of drug dependency or drug abuse. 
 

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Appendix H: 
Blood Pressure by Height and Age 
The tables for normal blood pressure 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 blood pressure (BP) is compared with the 
numbers provided in the table (boys or girls) for age and height percentile. 
• The child is normotensive if BP is below the 90th percentile. 
• 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. 
• 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.  
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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Appendix I: 
Serum Creatinine Clearance Calculation 
According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; 
https://www.niddk.nih.gov/health-information/professionals/clinical-tools-patient-
management/kidney-disease/laboratory-evaluation/glomerular-filtration-rate-calculators/ckd-
epi-adults-conventional-units) in adults, the most widely-used equations for estimating 
glomerular filtration rate (GFR) from serum creatinine are the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) equation and the isotope dilution mass spectrometry 
(IDMS) traceable Modification of Diet in Renal Disease (MDRD) Study equation. 
This CKD-EPI equation calculator should be used when Scr is reported in mg/dL. This 
equation is recommended when eGFR values above 60 mL/min/1.73 m² are desired. 
GFR = 141 × min(Scr/κ, 1)α × max(Scr/κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if 
African American] 
Where: 
• Scr is serum creatinine in mg/dL, 
• κ is 0.7 for females and 0.9 for males, 
• α is -0.329 for females and -0.411 for males, 
• min indicates the minimum of Scr/κ or 1, and 
• max indicates the maximum of Scr/κ or 1. 
The equation does not require weight because the results are reported normalized to 1.73 m² 
BSA, which is an accepted average adult surface area. 
The GFR estimate should be calculated by CKD-EPI equation using the Merck Manual 
Calculator: 
https://www.merckmanuals.com/professional/multimedia/clinical-calculator/glomerular-
filtration-rate-estimate-by-ckd-epi-equation 

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Appendix J: 
Body Surface Area (BSA) Calculation 
Body Surface Area (BSA) will be calculated using the Mosteller Method*: 
BSA (m2) = (height (cm) × weight (kg)/3600)½ 
Also expressed as: 
BSA (m2) = square root of (height (cm) x weight (kg)/3600) 
*Mosteller RD. Simplified calculation of body surface area. N Engl J Med. 1987;317:1098.