Conditions: Advanced Solid Tumor BRAF Gene Mutation BRAF Gene Alteration MEK Mutation MEK Alteration MAP2K1 Gene Mutation MAP2K1 Gene Alteration MAP2K2 Gene Mutation MAP2K2 Gene Alteration
Keywords: atypical BRAF, non-V600
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 104
Healthy volunteers: no

Brief summary:
This BVD-523-ABC study builds on the safety and clinical activity experience of previous studies that have evaluated ulixertinib as a novel targeted cancer treatment in cohorts of patients with specific genetic alterations and tumor histologies that result in aberrant MAPK pathway signaling. Early clinical data have demonstrated anti-tumor activity with ulixertinib treatment and have identified specific groups of patients for whom additional development is warranted.

Detailed description:
This multi-center, phase II study will be conducted in two parts and assess the clinical benefit, safety, pharmacokinetics, and pharmacodynamics of ulixertinib (BVD-523) in patients with advanced malignancies.

Part A (tumor histology agnostic) will be open label and enroll patients to one of six groups based on their tumor alteration. Targeted enrollment per group was 38 patients with a total targeted enrollment of 228 patients. Actual enrollment was total of 104 patients with 77 patients allocated to treatment.

* Group 1: Patients with tumors, other than colorectal cancer (CRC), having a BRAF alteration that results in an amino acid change at positions G469, L485, or L597.
* Group 2: Patients with tumors, other than CRC, having a defined Class 2 BRAF alteration (see Appendix 2 of protocol).
* Group 3: Patients with tumors, other than CRC, having an atypical BRAF alteration (non V600) that is not specified in Group 1 or Group 2.
* Group 4: Patients with CRC having any atypical BRAF alteration.
* Group 5: Patients with tumors, other than CRC, harboring alterations in MEK1/2.
* Group 6: Patients with CRC harboring alterations in MEK1/2.

Part B (tumor histology specific) will randomly enroll patients with one of up to three specified tumor histologies to receive either ulixertinib or the physician's choice of treatment in a 2:1 ratio. Tumors must harbor a specified MEK or atypical BRAF alteration. If a patient progresses on physician's choice of treatment, crossover to the ulixertinib arm is permitted.The specific histologies to be included in this part will be selected based on available data and discussion with the clinical investigators, the medical monitor, and the sponsor. Total enrollment was targeted to approximately 80-100 patients per histology with up to three histologies included; however, the study was terminated prior to any patients enrolling in Part B.

Arms:
arm 1: Oral, 600 mg, twice daily, for 28-days in each treatment cycle arm 2: Oral, 600 mg, twice daily, for 28-days in each treatment cycle arm 3: Physician's choice will be restricted to two approved (not off-label) treatments for each tumor histology (agents targeting BRAF or MEK kinases and experimental agents are not permitted as physician choice). If a patient progresses on physician's choice of treatment, crossover to the ulixertinib arm is permitted.

Interventions: intervention 1: Ulixertinib intervention 2: Physician's Choice
Intervention descriptions: intervention 1: Oral, 600 mg, twice daily, for 28-days in each treatment cycle intervention 2: Physician's choice will be restricted to two approved (not off-label) treatments for each tumor histology (agents targeting BRAF or MEK kinases and experimental agents are not permitted as physician choice)).

Protocol document:
Prot_000.pdf: 
BVD-523-ABC 
 
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CLINICAL STUDY PROTOCOL 
 
A Two-Part, Phase II, Multi-center Study of the ERK 
Inhibitor Ulixertinib (BVD-523) for Patients with Advanced 
Malignancies Harboring MEK or Atypical BRAF Alterations 
Protocol Number: BVD-523-ABC 
 
National Clinical Trial (NCT) 
Identified Number:  
NCT04488003 
IND Sponsor:  
BioMed Valley Discoveries, Inc. 
 
4435 Main Street, Suite 550 
 
Kansas City, MO 64111 
 
Medical Monitor: 
Cmed Inc. 
4000 Aerial Center Parkway 
Suite 102 
Morrisville, NC 27560 
 
Protocol Version: 
1.0 
Date:  
01 JUN 2020 
 
 
CONFIDENTIAL INFORMATION 
This document is the sole property of BioMed Valley Discoveries, Inc. This 
document and any and all information contained herein has to be considered 
and treated as strictly confidential. This document shall be used only for the 
purpose of the disclosure herein provided. No disclosure or publication shall 
be made without the prior written consent of BioMed Valley Discoveries, Inc. 


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PROTOCOL APPROVAL SIGNATURE PAGE 
SPONSOR: BIOMED VALLEY DISCOVERIES, INC 
I have read and understand the contents of Version 1.0 of this clinical protocol for 
Study No. BVD-523-ABC dated 01 Jun 2020 and I agree to meet all obligations of the 
sponsor as detailed in all applicable regulations and guidelines. In addition, I will inform 
the Principal Investigator and all other investigators of all relevant information that 
becomes available during the conduct of this study. 
Approved By: 
 
 
 
 
 
Brent L. Kreider, PhD. 
Chief Operations Officer, BioMed Valley Discoveries, Inc. 
 
Date 
 
 


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PRINCIPAL INVESTIGATOR’S AGREEMENT 
I have read and understand the contents of Version 1.0 of this clinical protocol for 
Study No. BVD-523-ABC dated 01 Jun 2020 and will adhere to the study requirements 
as presented, including all statements regarding confidentiality. In addition, I will 
conduct the study in accordance with current Good Clinical Practices and applicable 
FDA regulatory requirements: 
Principal Investigator: 
Name:   
 
Title:   
 
Institution:    
Address:    
Address: 
 
Phone:  
 
Fax:  
 
 
 
 
 
 
 
 
  
Signature 
 Date 
 
 


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Table of Contents 
1 
STATEMENT OF COMPLIANCE ..................................................................... 11 
2 
ABBREVIATIONS AND DEFINITION OF TERMS ............................................ 12 
3 
PROTOCOL SUMMARY .................................................................................. 16 
3.1 
Synopsis .................................................................................................. 16 
3.2 
Schema .................................................................................................... 21 
3.3 
Schedule of Activities (SoA) ..................................................................... 21 
4 
INTRODUCTION .............................................................................................. 25 
4.1 
Study Rationale ....................................................................................... 25 
4.2 
Background .............................................................................................. 25 
4.2.1 
Potential Risk .................................................................................. 27 
4.2.2 
Pharmacology Studies .................................................................... 31 
4.2.3 
Toxicity and Safety Studies ............................................................. 34 
4.2.4 
Previous Human Experience .......................................................... 35 
5 
OBJECTIVES AND ENDPOINTS ..................................................................... 42 
5.1 
Part A – Tumor Histology Agnostic .......................................................... 42 
5.1.1 
Primary Objective ............................................................................ 42 
5.1.2 
Secondary Objectives ..................................................................... 42 
5.1.3 
Exploratory Objectives .................................................................... 42 
5.2 
Part B – Tumor Histology Specific ........................................................... 43 
5.2.1 
Primary Objective ............................................................................ 43 
5.2.2 
Secondary Objectives ..................................................................... 43 
6 
STUDY DESIGN ............................................................................................... 44 
6.1 
Overall Design ......................................................................................... 44 
6.1.1 
Part A: Tumor Histology Agnostic ................................................... 44 
6.1.2 
Part B: Tumor Histology Specific .................................................... 44 
6.2 
Justification for Dose................................................................................ 44 
6.3 
Number of Patients .................................................................................. 45 
6.4 
Number of Study Sites ............................................................................. 45 
6.5 
Study Duration and End of Study Definition ............................................. 45 
7 
STUDY POPULATION ..................................................................................... 46 
7.1 
Inclusion Criteria ...................................................................................... 46 
7.2 
Exclusion Criteria ..................................................................................... 47 
7.3 
Screen Failures ........................................................................................ 48 
7.4 
Strategies for Recruitment and Retention ................................................ 48 


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STUDY DRUG .................................................................................................. 49 
8.1 
Study Drug(s) Administration ................................................................... 49 
8.1.1 
Study Drug Description ................................................................... 49 
8.1.2 
Dosing and Administration .............................................................. 49 
8.1.3 
Dose Interruptions and Adjustments ............................................... 49 
8.2 
Accountability/Appearance/Storage ......................................................... 49 
8.2.1 
Acquisition and Accountability ........................................................ 49 
8.2.2 
Formulation, Appearance, Packaging, and Labeling....................... 50 
8.2.3 
Product Storage and Stability ......................................................... 50 
8.3 
Randomization ......................................................................................... 50 
8.4 
Study Drug Compliance ........................................................................... 51 
8.5 
Concomitant Therapy and Rescue Medication ........................................ 51 
9 
STUDY DRUG DISCONTINUATION AND PATIENT 
DISCONTINUATION/WITHDRAWAL ............................................................... 52 
9.1 
Discontinuation of Study Drug ................................................................. 52 
9.2 
Patient Discontinuation Criteria ................................................................ 52 
9.3 
Patient Withdrawal From the Study ......................................................... 52 
9.4 
Long Term Follow Up............................................................................... 53 
9.5 
Lost to Follow-up ..................................................................................... 53 
10 STUDY ASSESSMENTS AND PROCEDURES ............................................... 55 
10.1 Methods of Assessment and Criteria for Evaluation ................................ 55 
10.1.1 
Demographic Data .......................................................................... 55 
10.1.2 
Medical and Cancer History ............................................................ 55 
10.1.3 
Prior and Concomitant Medications ................................................ 55 
10.1.4 
Vital Signs and Physical Examination ............................................. 55 
10.1.5 
Ophthalmology Examination ........................................................... 56 
10.1.6 
Laboratory Assessments ................................................................ 56 
10.1.7 
Electrocardiogram (ECG) ................................................................ 57 
10.1.8 
Echocardiogram (ECHO) or Multi-Gated Acquisition (MUGA) ........ 57 
10.1.9 
Disease Status ................................................................................ 57 
10.1.10 Tissue Biopsy ................................................................................. 57 
10.1.11 Blood Samples for Pharmacokinetic (PK) Analysis ......................... 58 
10.1.12 Blood Samples for Pharmacodynamic (PD) and ctDNA Analysis ... 58 
10.1.13 Adverse Events ............................................................................... 58 
10.2 Criteria for Evaluation .............................................................................. 58 
10.2.1 
Efficacy ........................................................................................... 58 


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10.2.2 
Pharmacokinetics (PK) ................................................................... 59 
10.2.3 
Circulating Tumor DNA ................................................................... 59 
10.2.4 
Pharmacodynamics (PD) ................................................................ 59 
10.3 Description of Study Visits for Patients Receiving Ulixertinib ................... 59 
10.3.1 
Description of Study Visits for Cycle 1 ............................................. 59 
10.3.2 
Description of Study Visits for Cycle 2 ............................................. 63 
10.3.3 
Cycle 3 and Subsequent Cycles Visit (Day 1 ± 3 of each cycle) ..... 63 
10.3.4 
Description of Study Visits for Patients Enrolled in Part B and 
Receiving Physician’s Choice of Treatment .................................... 64 
10.3.5 
End of Treatment Visit .................................................................... 64 
10.3.6 
Safety Follow-Up Assessment ........................................................ 65 
10.3.7 
Follow Up ........................................................................................ 65 
10.3.8 
Unscheduled Visits ......................................................................... 65 
10.4 Adverse Events and Serious Adverse Events .......................................... 66 
10.4.1 
Definition of Adverse Events (AE) ................................................... 66 
10.4.2 
Definition of Serious Adverse Events (SAE) ................................... 66 
10.4.3 
Classification of an Adverse Event .................................................. 67 
10.4.4 
Time Period and Frequency for Event Assessment and Follow-up. 68 
10.4.5 
Adverse Event Reporting ................................................................ 69 
10.4.6 
Serious Adverse Event Reporting ................................................... 69 
10.4.7 
Overdose ........................................................................................ 70 
10.4.8 
Reporting of Pregnancy .................................................................. 70 
11 STATISTICAL CONSIDERATIONS .................................................................. 72 
11.1 Statistical Analysis Plan ........................................................................... 72 
11.2 Sample Size Determination ..................................................................... 72 
11.2.1 
Part A .............................................................................................. 72 
11.2.2 
Part B .............................................................................................. 72 
11.3 Randomization ......................................................................................... 72 
11.4 Analysis Sets ........................................................................................... 73 
11.4.1 
Full Analysis Set ............................................................................. 73 
11.4.2 
Safety Analysis Set ......................................................................... 73 
11.4.3 
Per Protocol Analysis Set ............................................................... 73 
11.5 Data Presentation .................................................................................... 73 
11.5.1 
Demographic .................................................................................. 73 
11.5.2 
Baseline Characteristics ................................................................. 74 
11.5.3 
Medical History and Physical Examination ..................................... 74 


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11.5.4 
Concomitant Medications or Treatments ........................................ 74 
11.5.5 
Efficacy Analysis ............................................................................. 74 
11.5.6 
Pharmacokinetic (PK) / Pharmacodynamic (PD) Data .................... 76 
11.5.7 
Safety Analysis ............................................................................... 76 
11.6 Interim Analysis ....................................................................................... 77 
11.7 Changes in the Conduct of the Study or Planned Analysis ...................... 77 
12 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ......................................................................................... 78 
12.1 Regulatory, Ethical, and Study Oversight Considerations........................ 78 
12.1.1 
Informed Consent Process ............................................................. 78 
12.1.2 
Study Discontinuation and Closure ................................................. 78 
12.1.3 
Confidentiality and Privacy .............................................................. 79 
12.1.4 
Future Use of Stored Specimens and Data .................................... 80 
12.1.5 
Key Roles and Study Governance .................................................. 81 
12.1.6 
Auditing Procedure ......................................................................... 82 
12.1.7 
Data Handling and Record Keeping ................................................ 83 
12.1.8 
Protocol Deviations ......................................................................... 84 
12.1.9 
Publication and Data Sharing Policy ............................................... 84 
12.1.10 Conflict of Interest Policy ................................................................ 84 
12.1.11 Insurance ........................................................................................ 84 
12.2 Protocol Amendment History ................................................................... 85 
13 REFERENCES ................................................................................................. 86 
 


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List of In-Text Tables 
Table 3.1 
Part A and B: Schedule of Activities ..................................................... 22 
Table 4.1 
Previous Human Experience with Ulixertinib ........................................ 36 


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List of In-Text Figures 
Figure 4.1 BVD-523 Displays Dose Dependent Efficacy in the Murine 
Xenograft Model of Human BRAF-Mutant Melanoma Cell Line 
A375 ...................................................................................................... 32 
Figure 4.2 Mean Tumor Volume Plot; BVD-523 and Dabrafenib Combination 
Demonstrates Superior Efficacy Compared to Either Single Agent 
Alone in the A375 BRAF Mutant Melanoma Xenograft Model .............. 33 
Figure 4.3 Kaplan-Meyer Plot; BVD-523 and Dabrafenib Combination 
Demonstrates Superior Survival Compared to Either Single Agent 
Alone in the A375 BRAF Mutant Melanoma Xenograft Model .............. 33 
Figure 4.4 Percent Target Lesion Change in Patients from BVD-523-01 with 
BRAF non-V600 mutations ................................................................... 40 
Figure 4.5 Study Durations of Patients from BVD-523-01 with BRAF non-
V600 mutations ..................................................................................... 41 
 


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List of Appendices 
Appendix 1 Non-Permitted Concomitant Medications ............................................. 88 
Appendix 2 List of Accepted Atypical BRAF Type II Alterations for Group 2 ........... 89 
Appendix 3 ECOG Performance Status ................................................................... 90 
 
 
 


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1 
STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with International Conference on 
Harmonization Good Clinical Practice (ICH GCP) and the applicable United States 
(US) Code of Federal Regulations (CFR). The principal investigator will assure that 
no deviation from, or changes to the protocol will take place without prior agreement 
from the Investigational New Drug (IND) or Investigational Device Exemption (IDE) 
sponsor, funding agency and document approval from the Institutional Review Board 
(IRB), except where necessary to eliminate an immediate hazard(s) to the trial 
participants. All personnel involved in the conduct of this study have completed 
Human Subjects Protection and ICH GCP Training. 
The protocol, informed consent form(s), recruitment materials, and all participant 
materials will be submitted to the IRB for review and approval. Approval of both the 
protocol and the consent form must be obtained before any participant is enrolled. Any 
amendment to the protocol will require review and approval by the IRB before the 
changes are implemented to the study. All changes to the consent form will be IRB 
approved; a determination will be made regarding whether a new consent needs to 
be obtained from participants who provided consent, using a previously approved 
consent form. 
 


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2 
ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Definition 
%F 
Absolute bioavailability 
°F 
Degrees Fahrenheit 
µg 
Microgram 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine transaminase (SGPT) 
AML 
Acute myeloid leukemia 
AST 
Aspartate transaminase (SGOT) 
AUC 
Area under the plasma concentration-time curve 
BCVA 
Best-corrected visual acuity  
b.i.d. 
Twice daily 
BOR 
Best overall response 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
cm 
Centimeter 
Cmax 
Maximum concentration 
CMC 
Carboxymethylcellulose 
CMP 
Clinical Monitoring Plan 
CNS 
Central nervous system 
CONSORT 
Consolidated Standards of Reporting Trials 
CR 
Complete remission/complete response 
CRC 
Colorectal cancer 
CRF 
Case report form 
CRO 
Clinical Research Organization 
CRp 
Complete remission with incomplete platelet recovery 
CSR 
Central serous retinopathy 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
ctDNA 
Circulating tumor DNA 
CYP 1A2 
Cytochrome P450 isoform 1A2 
CYP 2D6 
Cytochrome P450 isoform 2D6 
CYP 3A4 
Cytochrome P450 isoform 3A4 
dL 
Deciliter 
DLT 
Dose limiting toxicity 
DOB 
Date of birth 
DOR     
Duration of response 
DSPV 
Drug Safety and Pharmacovigilance                  
DUSP 
Dual-specificity phosphatase 
EC 
Ethics Committee 


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Abbreviation 
Definition 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EDTA 
Ethylenediaminetetraacetic acid 
EOS 
End-of-study 
EOT 
End of treatment 
ERK 
Extracellular signal-regulated kinase 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
g 
Gram 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GI 
Gastrointestinal 
GLP 
Good Laboratory Practice 
hCG 
Human chorionic gonadotropin 
HCl 
Hydrochloride 
HDPE 
high-density polyethylene 
hERG 
Human ether-a-go-go related gene  
IC50 
Half maximal inhibitory concentration 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IRB 
Institutional Review Board 
IST 
Investigator sponsored trial 
ITT 
Intent-to-treat 
IxRS 
Interactive Voice/Web Response System 
kg 
Kilogram 
LD 
Largest diameter 
LDH 
Lactate dehydrogenase 
LS 
Least squares 
LVEF 
Left ventricular ejection fraction 
MAPK 
Mitogen-activated protein kinase 
MDS 
Myelodysplastic syndrome 
MedDRA® 
Medical Dictionary for Regulatory Activities 
MEK 
Mitogen-activated protein kinase/extracellular signal-related kinase 
mg 
Milligram  
mL 
Milliliter  
MRI 
Magnetic Resonance Imaging 
MTD 
Maximum tolerated dose 
MUGA 
Multi-gated acquisition 
NCI 
National Cancer Institute 


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Abbreviation 
Definition 
ng 
Nanogram 
NOS 
Not otherwise specified 
NSCLC 
Non-small cell lung cancer 
ORR 
Overall response rate 
OS 
Overall survival 
PD 
Pharmacodynamics 
PFS 
Progression-free survival 
PI 
Principal Investigator 
PIC 
Powder-in-capsule 
PK 
Pharmacokinetics 
PP 
Per protocol 
PR 
Partial response 
PT 
Prothrombin time 
QC 
Quality Control 
QT 
A measure between Q and T waves in heart electrical system 
QTc 
Corrected QT interval 
QTcF 
Fridericia-corrected QT interval 
R2PD 
Recommended Phase 2 Dose 
RBC 
Red blood cell 
RECIST 
Response evaluation criteria in solid tumors (Version 1.1) 
RNA 
Ribonucleic Acid 
RP2D 
Recommended Phase 2 dose 
RPPA 
Reverse Phase Protein Arrays 
RSK 
Ribosomal S6 kinase 
RTK 
Receptor tyrosine kinase 
RVO 
Retinal vein occlusion 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis Systems 
SD 
Standard deviation 
SEM 
Standard error of the mean  
SMC 
Safety Monitoring Committee 
SoA 
Schedule of Activities 
SoC 
Standard of care 
SOP 
Standard Operating Procedure 
TEAE 
Treatment emergent adverse event 
TESAE 
Treatment emergent serious adverse event 
TFS 
Tumor-free survivors 
TGD 
Tumor growth delay 
TGI 
Tumor growth inhibition 
TTE 
Time to endpoint 
ULN 
Upper limit of normal 


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Abbreviation 
Definition 
UV 
Ultraviolet 
VF 
Visual field 
WBC 
White blood cell 
WHO 
World Health Organization 
 
 
 


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3 
PROTOCOL SUMMARY 
3.1 
SYNOPSIS 
Sponsor: 
BioMed Valley Discoveries, 
Inc. 
Investigational Product: 
Ulixertinib (BVD-523) 
Developmental Phase:   
Phase II 
Protocol Number: 
BVD-523-ABC 
Title of Study: 
A two-part, phase II, multi-center study of the ERK inhibitor ulixertinib (BVD-523) for patients with 
advanced malignancies harboring MEK or atypical BRAF alterations. 
Study Description: 
BVD-523-ABC is a multi-center, phase II study that will be conducted in two parts. 
Patients will receive twice daily oral doses of ulixertinib in 28-day treatment cycles until disease 
progression, unacceptable toxicity, consent is withdrawn, or another withdrawal criterion is met. 
Treatment cycles will occur consecutively without interruption except when necessary to manage 
adverse events (AEs). 
Part A (tumor histology agnostic) will be open label and enroll patients to one of six groups 
based on their tumor alteration: 
• 
Group 1: Patients with tumors, other than colorectal cancer (CRC), having a BRAF 
alteration that results in an amino acid change at positions G469, L485, or L597. 
• 
Group 2: Patients with tumors, other than CRC, having a defined Class 2 BRAF alteration 
(see Appendix 2). 
• 
Group 3: Patients with tumors, other than CRC, having an atypical BRAF alteration (non 
V600) that is not specified in Group 1 or Group 2. 
• 
Group 4: Patients with CRC having any atypical BRAF alteration. 
• 
Group 5: Patients with tumors, other than CRC, harboring alterations in MEK1/2. 
• 
Group 6: Patients with CRC harboring alterations in MEK1/2. 
Part B (tumor histology specific) will randomly enroll patients with one of up to three specified 
tumor histologies to receive either ulixertinib or the physician’s choice of treatment in a 2:1 ratio 
(physician’s choice will be restricted to two approved (not off-label) treatments for each tumor 
histology (agents targeting BRAF or MEK kinases and experimental agents are not permitted as 
physician choice)). Tumors must harbor a specified MEK or atypical BRAF alteration. If a patient 
progresses on physician’s choice of treatment, crossover to the ulixertinib arm is permitted.   
The specific histologies to be included in this part will be selected based on available data and 
discussion with the clinical investigators, the medical monitor, and the sponsor. 
 
 
 
 


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Sponsor: 
BioMed Valley Discoveries, 
Inc. 
Investigational Product: 
Ulixertinib (BVD-523) 
Developmental Phase:   
Phase II 
Objectives and Endpoints: 
Part A – Tumor histology agnostic 
• 
Primary: To assess the clinical benefit of ulixertinib as measured by the overall response 
rate (ORR) in patients receiving ulixertinib that have advanced malignancies harboring a 
MEK or atypical BRAF alteration. 
ORR will be defined as the percentage of patients achieving a Best Overall Response 
(BOR) of confirmed Complete Response (CR) and/or Partial Response (PR), according to 
RECIST 1.1. 
• 
Secondary:  
o 
To evaluate the safety profile of ulixertinib per CTCAE v5.0, including term, 
incidence, severity, and duration of AEs. 
o 
To assess the duration of response (DOR), according to RECIST 1.1. 
o 
To assess the progression free survival (PFS), according to RECIST 1.1 and 
overall survival (OS) over 18 months. 
o 
To measure the blood levels of ulixertinib and selected metabolites: 
Pharmacokinetic profile of ulixertinib (BVD-523) and selected metabolites. 
• 
Exploratory:  
o 
To evaluate the effects of ulixertinib on pharmacodynamic markers: ctDNA tissue 
biopsies, and/or blood to assess biomarkers. Assays include, but are not limited 
to, phosphorylation of RSK from whole blood, Reverse Phase Protein Arrays 
(RPPA) to assess protein levels, e.g. DUSP 4/6, plus Nanostring and/or RNA-
exome to assess mRNA expression in tissue pre- and post-ulixertinib treatment. 
Part B – Tumor histology specific 
• 
Primary: To assess PFS in patients receiving ulixertinib in defined tumor histologies (up to 
three histologies to be selected) compared to physician’s choice of treatment. Patient’s 
tumors must harbor a specified MEK or atypical BRAF alteration.  
PFS will be defined as the time from first day of trial medication to disease progression 
according to RECIST 1.1, or death. 
• 
Secondary:  
o 
To evaluate the safety profile of ulixertinib per CTCAE v5.0, including term, 
incidence, severity, and duration of AEs. 
o 
To assess OS over 18 months in patients receiving ulixertinib with a defined tumor 
histology and a MEK or atypical BRAF alteration, compared to physician’s choice 
of treatment. 
o 
To determine ORR and DOR in patients receiving ulixertinib with a defined tumor 
histology and a MEK or atypical BRAF alteration, according to RECIST 1.1, 
compared to physician’s choice of treatment. 
Study Population - Criteria for Inclusion: 
Patients must meet all of the inclusion criteria to be eligible. 
1. Patients with a locally advanced or metastatic malignancy, that has progressed following 
systemic therapy for their disease, if available, or for which the patient is not a candidate or 
refuses.  
2. Tumors harboring a MEK or atypical BRAF alteration.  


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Sponsor: 
BioMed Valley Discoveries, 
Inc. 
Investigational Product: 
Ulixertinib (BVD-523) 
Developmental Phase:   
Phase II 
3. Provide signed and dated informed consent prior to initiation of any study-related procedures 
that are not considered standard of care (SoC). 
4. Male or female patients aged ≥18 years. 
5. Patients must have measurable disease by RECIST version 1.1. 
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2. 
7. Adequate renal function [creatinine ≤1.5 times ULN (upper limit of normal)] or a glomerular 
filtration rate (GFR) of ≥50 mL/min (using Cockcroft-Gault). 
8. Adequate hepatic function [total bilirubin ≤1.5 times ULN; AST (aspartate transaminase) and 
ALT (alanine transaminase) ≤3 times ULN or ≤5 times ULN if the elevation is due to liver 
involvement by tumor]. 
9. Adequate bone marrow function (hemoglobin ≥9.0 g/dL; platelets ≥100 x 109 cells/L; absolute 
neutrophil count ≥1.5 x 109 cells/L). 
10. Adequate cardiac function:  
• 
Left ventricular ejection fraction (LVEF) of >50% as assessed by multi-gated 
acquisition (MUGA) or ultrasound/echocardiography (ECHO); and  
• 
A corrected QT interval (QTc) <480ms by the Fridericia method (QTcF).  
11. Contraception: 
• 
For women: Negative pregnancy test for females of child-bearing potential; must be 
surgically sterile, postmenopausal (no menstrual cycle for at least 12 consecutive 
months), or compliant with a medically approved contraceptive regimen during and for 
3 months after the last administration of study drug. Abstinence is not considered an 
adequate contraceptive regimen. 
• 
For men: Must be surgically sterile, or compliant with a medically approved 
contraceptive regimen during and for 3 months after the last administration of study 
drug. 
12. Willing and able to participate in the trial and comply with all trial requirements. 
13. Patients with a prior or concurrent malignancy whose natural history or treatment does not 
have the potential to interfere with the safety or efficacy assessment of the investigational 
agent may be included after consultation with the medical monitor. 
Study Population - Criteria for Exclusion: 
Patients who fulfill one or more of the following criteria will not be eligible for inclusion in this trial: 
1. Gastrointestinal (GI) condition that could impair absorption of study medication (specific cases 
e.g., remote history of GI surgery, may be enrolled after discussion with the medical monitor) 
or inability to ingest study medication. 
2. Uncontrolled or severe intercurrent medical condition. 
3. Known uncontrolled brain metastases. Stable brain metastases either treated or being treated 
with a stable dose of steroids/anticonvulsants, with no dose change in the previous 4 weeks, 
can be allowed. 
4. Having received any cancer-directed therapy (chemotherapy, hormonal therapy, biologic or 
immunotherapy, etc.) within 28 days or 5 half-lives (whichever is shorter) prior to the first dose 
of study drug. Patients previously treated with radiotherapy must have recovered from the 
acute toxicities associated with such treatment. 


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Sponsor: 
BioMed Valley Discoveries, 
Inc. 
Investigational Product: 
Ulixertinib (BVD-523) 
Developmental Phase:   
Phase II 
5. Major surgery within 4 weeks prior to first dose. 
6. Any use of an investigational drug within 28 days or 5 half-lives (whichever is shorter) prior to 
the first dose of study drug. A minimum of 10 days between termination of the prior 
investigational drug and administration of study drug is required. In addition, any drug-related 
toxicity except alopecia should have recovered to Grade 1 or less.  
7. Prior therapy with any ERK inhibitor (e.g. LY3214996, LTT462).   
8. Groups 1-4: Prior therapy with any BRAF and/or MEK inhibitor (e.g. encorafenib, dabrafenib, 
vemurafenib, binimetinib, trametinib, cobimetinib) is excluded. Prior BRAF and/or MEK 
inhibitor therapy is permitted for Groups 5 and 6. 
9. For Part B, agents targeting BRAF or MEK kinases and experimental agents are not permitted 
as physician’s choice  
10. Pregnant or breast-feeding women. 
11. Any evidence of serious active infections. Patients are allowed to enroll if they have been 
fever-free for at least 48 hours and are on an active treatment that is not prohibited in 
Appendix 1. 
12. Any important medical illness or abnormal laboratory finding that would increase the risk of 
participating in this study (based on the investigator’s judgment).  
13. A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy 
(CSR). 
14. Concurrent therapy with any other investigational agent. 
15. Concurrent therapy with drugs known to be strong inhibitors or inducers of CYP1A2, CYP2D6, 
and CYP3A4. 
Concomitant Medications: 
Necessary supportive care such as antibiotics, blood product transfusions, antiemetics, 
antidiarrheals, etc., will be allowed. Drugs that are strong inhibitors or inducers of CYP1A2, 
CYP2D6, and CYP3A4 will not be allowed during the study (see Appendix 1). 
Description of Sites/Facilities Enrolling Patients: 
The study will take place at sites within the United States. Approximately, up to 25 sites will be 
utilized, however, because the patient population is relatively rare, clinical sites may need to be 
added as qualifying patients are found. Clinical trial networks may be utilized. 
Description of Study Drug: 
Ulixertinib (BVD-523), 600 mg formulated blend, taken orally, with food, twice-daily for each 28-day 
cycle. 
Study Duration: 
Approximately 38 months. 
Patient Number: 
Total enrollment for Part A is targeted at approximately 228 patients with 38 patients per group. 
Additional patients may be enrolled as appropriate. 
Total enrollment for Part B is targeted to approximately 80-100 patients per histology with up to 
three histologies included; however, additional patients may be enrolled.  


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Sponsor: 
BioMed Valley Discoveries, 
Inc. 
Investigational Product: 
Ulixertinib (BVD-523) 
Developmental Phase:   
Phase II 
Patient Duration: 
Each patient will continue on study therapy until documented disease progression, intolerable 
toxicity, study closure, or until other treatment discontinuation criteria is met. Patients who 
discontinue study therapy prior to disease progression, will continue to be followed for progression. 
It is estimated that participants will be on study for up to 30 months. 
Statistical analysis: 
The Full Analysis Set (FAS) will include all patients who received at least one dose of study 
medication. For Part B, analyses performed on the FAS will allocate patients’ treatment group as 
randomized. 
The safety analysis set will include all patients who received at least one dose of study medication. 
For Part B, analyses performed on the safety population will allocate patients’ treatment group as 
actually received. 
The per-protocol (PP) analysis set will include all patients of the FAS who completed the study 
without any major protocol deviations. 
All analyses will be performed separately for Part A and Part B, and by group/tumor histology. 
Efficacy analysis: 
The efficacy analysis will be performed on the FAS. 
ORR is defined as the percentage of patients achieving a BOR of confirmed complete response 
(CR) and/or partial response (PR) as assessed by the investigator for Part A, and both as 
assessed by the investigator and as adjudicated by the independent review committee for Part B.  
ORR will be calculated with the corresponding 95% confidence interval (CI). For Part B, ORR will 
be compared between ulixertinib and physician’s choice of treatment using a Chi square test. 
DOR is defined as the time from first response to disease progression or death. PFS is defined as 
the time from first day of trial medication to disease progression or death. OS is defined as the 
time from first day of trial medication to death. Censoring rules will be applied as appropriate. 
DOR, PFS, and OS will be analyzed using Kaplan-Meier estimates and curves, median PFS and 
respective 95% CIs. For Part B, DOR, PFS, and OS will be compared between ulixertinib and 
physician’s choice of treatment using a Log Rank test. These analyses will be performed based on 
investigator assessment for Part A, and both on adjudicated assessment by the independent 
review committee and on investigator assessment for Part B. 
Sensitivity analyses will be conducted. 
Safety analysis: 
The safety analysis will be performed on the safety analysis set. 
AEs, including treatment-emergent adverse event, AEs considered study drug-related, deaths, 
SAEs, and AEs resulting in study drug discontinuation, will be summarized (number and 
percentage of patients) by System Organ Class and Preferred Term. 
The parameters associated with the clinical laboratory tests (hematology, clinical chemistry, and 
urinalysis) will be summarized with descriptive statistics by visit and for the change from baseline 
to each planned post-baseline visit. Graded laboratory abnormalities will be defined using the 
grading scheme based on NCI CTCAE and summarized. Shift tables will also be produced. 


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Sponsor: 
BioMed Valley Discoveries, 
Inc. 
Investigational Product: 
Ulixertinib (BVD-523) 
Developmental Phase:   
Phase II 
Changes in the patient’s physical examination findings, vital sign parameters, and ECG will be 
summarized by group/tumor histology and overall, and any abnormal values will be tabulated. 
3.2 
SCHEMA 
 
 
 
3.3 
SCHEDULE OF ACTIVITIES (SOA) 
The Schedule of Activities (SoA) table (Table 3.1) provides an overview of the protocol 
visits and procedures. Refer to Section 10, Study Assessments and Procedures for 
detailed information on each assessment required for compliance with the protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in 
the SoA table in order to conduct evaluations or assessments required to protect the 
wellbeing of the patient. Every effort should be made to follow the SoA for the entire 
study. 
Group 1 (n=38)
•
Alterations at BRAF-G469, -
L485, or -L597
•
Any histology (excluding CRC)
Group 2 (n=38)
•
Defined class II BRAF 
alterations (see appendix 2)  
•
Any histology (excluding CRC)
Group 3 (n=38)
•
Any other atypical BRAF 
alteration
•
Any histology (excluding CRC)
Group 4 (n=38)
•
Any atypical BRAF alteration
•
CRC patients only
Group 5 (n=38)
•
MEK1/2 alteration
•
Any histology (excluding CRC)
Group 6 (n=38)
•
MEK1/2 alteration
•
CRC patients only
PART A
Ulixertinib 600 mg BID
PART B
Defined histology and alterations determined by Part A 
Randomized: Ulixertinib 600 mg BID or Physician's choice
1: Defined histology and alterations
Ulixertinib 600 mg BID
Physician’s choice
2: Defined histology and alterations
Ulixertinib 600 mg BID
Physician’s choice
3: Defined histology and alterations 
Ulixertinib 600 mg BID
Physician’s choice
2:1
2:1
2:1


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Table 3.1 
Part A and B: Schedule of Activities 
 
 
Cycle 1 
Day 1 through 28 
Cycle 2 
Day 29 through 56 
Cycle 3-X 
28-day cycles, visit 
on 1st day of cycle 
Post Treatment Period 
Visit 
1 
Screening 
2 
Baseline 
3 
Tx 
4 
Tx 
5 
Tx 
6 
Tx 
7 
Tx 
8 
 -X Tx 
End of 
Treatment 
(EOT) Visit 
Safety Follow-
Upa 
Follow-
Upb 
Visit Day 
-28 to -1 
1 ± 0 
8 ± 3 
15 ± 3 
29 ± 3 
36 ± 3 
43 ± 3 
57 ± 3 
<14 ± 3 days 
after last dose 
30 ± 3 days 
after last dose 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
Medical historyc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Cancer historyd 
X 
 
 
 
 
 
 
 
 
 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Measure height  
X 
 
 
 
 
 
 
 
 
 
 
Measure weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Physical examinatione 
X 
 
 
 
 
 
 
 
 
 
 
ECOG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Ophthalmology examf 
X 
 
 
 
 
 
 
 
 
 
 
Pregnancy testg,h 
X 
Xg 
 
 
Xh 
 
 
Xh 
Xh 
 
 
Clinical lab testsi, j 
X 
Xi 
X 
X 
X 
X 
X 
Xj 
X 
 
 
Electrocardiogram (ECG)k 
X 
 
 
 
 
 
 
 
 
 
 
ECHO cardiogram or 
MUGA 
X 
 
 
 
 
 
 
 
 
 
 
Assess current disease 
statusl 
X 
 
 
 
X 
 
 
X 
X 
 
Xm 
Study drug administrationn 
 
X 
 
X 
 
 
 
 
 
 
 
Adverse events (AEs) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 


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Table 3.1 
Part A and B: Schedule of Activities 
 
 
Cycle 1 
Day 1 through 28 
Cycle 2 
Day 29 through 56 
Cycle 3-X 
28-day cycles, visit 
on 1st day of cycle 
Post Treatment Period 
Visit 
1 
Screening 
2 
Baseline 
3 
Tx 
4 
Tx 
5 
Tx 
6 
Tx 
7 
Tx 
8 
 -X Tx 
End of 
Treatment 
(EOT) Visit 
Safety Follow-
Upa 
Follow-
Upb 
Obtain unused drug 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Compliance by pill count 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Study drug dispensed 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Part A Only 
Tissue biopsy, if 
indicatedo,p 
Xo 
 
 
 
X 
 
 
 
Xp 
 
 
Pharmacodynamic blood 
samplesq 
 
X 
 
X 
 
 
 
 
 
 
 
ctDNAr 
 
X 
 
X 
X 
 
 
 
X 
 
 
Pharmacokinetic sampless 
 
 
 
Xs 
 
 
 
 
 
 
 
Part B Only 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
Table footnotes: 
a 
Patients will return to the clinic or will be contacted for a safety follow-up assessment 30 days ± 3 days after the last dose of study drug was 
taken; or earlier if subsequent therapy for advanced malignancy is initiated prior to 30 days ± 3 days.   
b 
Patients or their legally authorized representatives will be contacted every three months (± 7 days) until death, end of the study, or patient 
withdrawal of consent, whichever comes first. Survival and subsequent treatment status may be collected by public records, medical records, 
or by contacting the patient or their legally authorized representative by phone. 
c 
Full medical history at screening, only review/update of history at subsequent visits. 
d 
Oncologic history of the malignancy under study including prior regimens (duration of therapy, best response on therapy, date of 
discontinuation, and reason for discontinuation), surgery, and radiation therapy. 
e 
Physical examinations should be symptom driven after the Screening Visit. 
f 
Ophthalmological examinations will be performed by an ophthalmologist at screening, and whenever clinically indicated. In Part B, only 
patients in the ulixertinib arm need an ophthalmological exam. See section 10.1.5 for a full description of tests.  
g 
ONLY if the screening serum pregnancy test was performed more than 1 day previously. 


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h 
After screening and baseline, if urine pregnancy test is positive, confirm with serum test. 
i 
Visit 2 clinical lab samples should be collected pre-dose if not done during Screening Visit within 72 hours of start of treatment. 
j 
Chemistry, hematology, and urinalysis. After Cycle 2, clinical labs to be performed prior to starting each new cycle or more frequently when 
clinically indicated at the investigator’s discretion. See section 10.1.6 for a full description of test.  
k 
Patients with a normal ECG in Cycle 1 do not need to have repeat ECGs in subsequent cycles. Patients should be supine for 5 minutes prior 
to the ECG. 
l 
Tumor assessments will be made prior to dose initiation, at Visit 5, and then every 2 cycles. Patients who discontinue treatment for reasons 
other than progression will have assessments at the EOT visit (unless their previous assessment was performed within 28 days). The same 
imaging modality used for an individual patient (i.e. CT or MRI) at Screening should be maintained throughout the study. 
m 
Patients that discontinue study treatment for any reason other than disease progression, must continue to have disease assessments every 8 
weeks (± 7 days) until disease progression or the initiation of subsequent anticancer therapy. 
n 
Study drug to be taken twice daily. The first dose should be taken in the clinic on days when PD sampling occurs i.e., Cycle 1/Visit 2 (Day 1) 
and Cycle 1/Visit 4 (Day 15), remaining doses on all other days to be self-administered by patient. 
o 
Tissue biopsy for Part A only. If a patient has undergone a biopsy within ≤ 6 months and has not received any anticancer treatment since 
undergoing the biopsy, archival tissue from this biopsy may be used to fulfill screening tissue requirements. 
p 
Tissue biopsy at final study visit/at progression is optional, but strongly encouraged to help elucidate mechanism of resistance. 
q 
Collect pre-dose and 4 hour +/- 10 mins post-dose blood samples for PD. 
r 
Collect plasma for ctDNA.  
s 
Sample for PK should be collected pre-dose trough at steady state (patients who have received at least 5 days, or 10 consecutive doses, of 
study drug).   
 
 


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4 
INTRODUCTION 
4.1 
STUDY RATIONALE 
This BVD-523-ABC study builds on the safety and clinical activity experience of 
previous studies that have evaluated ulixertinib as a novel targeted cancer treatment 
in cohorts of patients with specific genetic alterations and tumor histologies that result 
in aberrant MAPK pathway signaling. Early clinical data have demonstrated anti-tumor 
activity with ulixertinib treatment and have identified specific groups of patients for 
whom additional development is warranted. 
4.2 
BACKGROUND 
Ulixertinib (BVD-523) is a small molecule inhibitor of extracellular signal-regulated 
kinase (ERK) family kinases (ERK1 and ERK2) that is being developed as a novel 
anti-cancer drug (Germann et al, 2017; Sullivan et al, 2018). ERK kinases are 
downstream components of the mitogen-activated protein kinase (MAPK) signaling 
cascade (RAS-RAF-MEK-ERK). Ulixertinib has demonstrated promising early efficacy 
for patients with tumors harboring alterations in the MAPK pathway, including atypical 
(non-V600) BRAF alterations, for which there are currently no approved targeted 
agents. This clinical protocol expands upon the ulixertinib Phase I signal to evaluate 
the utility of ulixertinib to treat patients with tumors harboring an atypical BRAF 
alteration. Furthermore, the potential to treat MEK1/2 mutant cancers will also be 
explored. This patient population is rare (<1% of cancers), however a strong scientific 
rationale exists to treat patients harboring putatively activating MEK1/2 alterations with 
ERK inhibition (Emery et al, 2017; Gao et al, 2018; Yaeger et al, 2019).      
The MAPK signaling cascade is among the most frequently mutated pathways in 
human cancer. Approximately 50% of melanoma patients possess a druggable 
hotspot V600E/K mutation in the BRAF protein kinase. FDA approvals of both immune 
system- (ipilimumab, nivolumab, and pembrolizumab) and signal transduction-
targeted (dabrafenib plus trametinib, vemurafenib plus cobimetinib, and encorafenib 
plus binimetinib) therapies have greatly expanded the armamentarium available for 
treating BRAF V600 mutation-dependent cancers.  
Atypical BRAF alterations (non-V600) are found in many cancers and are more 
prevalent than V600 mutations in certain tumor types. For example, between 50–80% 
of BRAF mutations in non-small cell lung cancer (NSCLC) and 22–30% in colorectal 
cancer (CRC) encode for BRAF non-V600 alterations (Danker et al, 2018). As next 
generation sequencing becomes standard clinical practice, oncologists are frequently 
identifying non-V600 BRAF alterations in their patients’ tumors. Unfortunately, there 
are no approved therapies targeting these alterations and thus there remains a lack 


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of viable therapeutic options that could be employed for optimal treatment of these 
patients.   
From recent studies, a new classification system is emerging for BRAF mutations 
based on biochemical and signaling mechanisms associated with these mutants (Yao 
et al, 2015; Yao et al, 2017; Dankner et al, 2018; Yaeger et al, 2019). Class I BRAF 
mutations affect amino acid V600 and signal as RAS-independent active monomers.  
While ulixertinib has demonstrated activity against MAPK pathway activity initiated by 
Class I BRAF mutations and thus may offer unique possibilities as single-agent or in 
combinations, these mutations are currently being addressed clinically with FDA 
approved inhibitors of BRAF plus MEK (dabrafenib plus trametinib, vemurafenib plus 
cobimetinib, and encorafenib plus binimetinib).   
Class II BRAF alterations function as RAS-independent activated dimers and are not 
addressed by available approved targeted therapies. Ulixertinib has demonstrated 
clinical activity against several of these class II BRAF alterations, across multiple 
tumor types (Sullivan et al, 2018).   
Class III BRAF alterations exhibit enhanced binding to RAS and wild-type RAF to 
signal as mutant BRAF-wild-type RAF dimers, thus amplifying the signaling 
downstream of RAS and thus require upstream activation to drive ERK signaling. For 
this reason, Class III BRAF alterations commonly co-occur in the context of other 
drivers of MAPK signaling, e.g. RAS mutation, NF1 loss, RTK activation.  
In human tumors the incidence of MEK1/2 mutations is rare (<1%). Similar to BRAF, 
a mechanism-based classification system has been proposed (Gao et al, 2018).  
Preclinical data has demonstrated activity of ulixertinib in MEK mutant models (Emery 
et al, 2017). 
In summary, ulixertinib, is a potent and selective inhibitor of the key MAPK pathway 
enzymes ERK1 and ERK2, has shown potent anti-tumor effects, including anti-cancer 
activity using in vitro cellular assays and in vivo tumor xenograft models. Our initial 
open-label, first-in-human clinical study (NCT01781429) with oral ulixertinib was 
conducted to identify the maximum tolerated dose (MTD) and the RP2D. Study aims 
also included assessment of the PK and pharmacodynamic properties of ulixertinib as 
well as preliminary efficacy in patients with genetic aberrations in BRAF (both V600 
and non-V600 amino acids), NRAS, and MEK. Consistent with current scientific 
understanding, class II BRAF mutations were demonstrated to be sensitive to single-
agent ulixertinib, largely independent of tumor type. In particular, non-V600 BRAF 
mutations, including G469A/V, L485W, and L597Q, across a variety of solid tumors, 
were shown to be clinically actionable for the first time, with durable objective 
responses.   


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The potential risk profile of ulixertinib is described in further detail in the following 
sections. 
4.2.1 
Potential Risk 
Preliminary evidence from in vitro and in vivo toxicological assessments of ulixertinib 
and data to-date from the experience in humans suggests the molecule has a safety 
profile supportive of its development as an anti-cancer therapeutic. Additionally, 
human clinical trials have been conducted using other drugs known to affect the MAPK 
pathway and findings from these studies may provide information regarding possible 
safety risks that may be mechanistically attributable to MAPK pathway inhibition.   
Thus, the risk profile for ulixertinib may potentially include the following: 
Dermatological Lesions 
Dermatological lesions have been seen in rodent GLP toxicology studies of ulixertinib.  
Several of the following findings displayed exposure-dependent increases in incidence 
and/or severity: non-specific dermal inflammation, pustular dermatitis, epidermal 
ulceration and acanthosis. These toxicities appeared to be associated with 
predominantly reversible pharmacodynamics, as the majority of findings were mild 
and/or of low incidence in animals that underwent dose cessation. 
In clinical studies, other drugs that inhibit components of the MAPK pathway exhibit 
cutaneous toxicity. Multiple investigational inhibitors of MEK1/2 kinases exhibit 
exposure- dependent, dose-limiting and reversible skin toxicities in a proportion of 
patients. Specific toxicities include: non-specific rash and pruritus, acneiform 
dermatitis, epidermal fissure, and paronychia. Additionally, clinical experience with 
both investigational agents and approved drugs that primarily target BRAF kinase 
have displayed exposure-dependent and reversible skin toxicities in a proportion of 
treated patients; relevant lesions here include keratoacanthoma-type squamous cell 
carcinomas, non-cancerous hyperkeratosis, and actinic keratosis.   
A similar pattern of cutaneous toxicity was observed in a subset of the patients treated 
in studies BVD-523-01 and BVD-523-02, with approximately 81% of patients in study 
BVD-523-01 and 38% in study BVD-523-02 experiencing TEAEs in the System Organ 
Class skin and subcutaneous tissue disorders, regardless of attribution. The TEAEs 
were most frequently rash (coded to various preferred terms), dermatitis acneiform, 
and pruritus; and one patient with a history of squamous cell carcinoma developed a 
keratoacanthoma while on treatment with ulixertinib. Rash has been treated with 
topical and/or oral agents (e.g., steroids), and dose reductions/interruptions as 
needed. One case of Stevens-Johnson syndrome assessed as possibly related to 
BVD-523, but confounded by concomitant medications, including an antibiotic, was 
reported in a 7 y.o. patient who was being treated for astrocytoma. Additionally, this 


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diagnosis was made clinically, without a biopsy. Discontinuations due to skin disorders 
have occurred but have been uncommon.  
Gastrointestinal Toxicity 
Preclinical toxicity studies of ulixertinib have provided evidence of exposure-related, 
reversible gastrointestinal toxicities, and these toxicities, including nausea, vomiting, 
and diarrhea, have also been observed at high frequency in the clinical program, in 
some cases occurring in association with dehydration and elevated creatinine/renal 
insufficiency. Nausea, vomiting, and diarrhea have been managed with ulixertinib 
dosing interruptions and supportive medications as needed and, in some cases, dose 
reduction of ulixertinib has been undertaken. Gastrointestinal hemorrhage (both upper 
and lower) has been reported in the ulixertinib program with the majority of events 
assessed as unrelated to study drug. The severity and reversibility of these non-
clinical and clinical toxicities, while not meriting a specific monitoring or treatment plan, 
warrant active routine monitoring of patients for this toxicity.  
General Disorders 
Study drug-related disorders characterized as general disorders, including fatigue, 
edema, and fever, have been observed in the ulixertinib program. In some patients, 
fatigue has been assessed as grade 3 in severity, but has not prompted study drug 
discontinuation. Events in the general disorders’ category have been managed 
variably with supportive medications and/or interruption of study drug administration 
until improvement or resolution. A Death (NOS) assessed as possibly related to 
ulixertinib and to metastatic duodenal carcinoma was reported in a 79-year-
old patient; no autopsy was performed.  
Hepatic and Renal Effects 
Study drug-related events of mild, moderate, and severe elevated AST and/or ALT 
have also been observed in the ulixertinib clinical program and were described as 
dose limiting toxicities (DLTs) in study BVD-523-01 at a dose of 900mg b.i.d. and in 
study BVD-523-02 at a dose of 750mg b.i.d. Drug-related events of elevated AST 
and/or ALT have been managed with interruptions of study drug followed in some 
instances by dose reduction. Study drug-related events of mild, moderate, and severe 
increased creatinine have also been observed, sometimes in conjunction with 
vomiting, diarrhea, and dehydration. Management has consisted of study drug 
interruption, rehydration, and, in some instances, dose reduction or discontinuation of 
study drug. 


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Hematological Effects 
Hematological effects observed in a rat repeat-dose study included lowered 
reticulocyte counts, mean corpuscular volume, platelet counts (in females only), and 
increased neutrophil, monocyte, basophil and large unstained cell counts. In dogs, the 
clinical pathology findings were consistent with inflammation (increased white blood 
cell count, neutrophils, fibrinogen and globulin), and decreased albumin and 
hemorrhage (decreased red cell mass). 
Hematologic effects in the ulixertinib clinical program have included, anemia, 
leukopenia, neutropenia, lymphopenia, and thrombocytopenia. One case of possibly 
related, grade 3, reversible, thrombotic thrombocytopenia purpura was reported in a 
patient with melanoma while receiving ulixertinib at a dose of 450mg b.i.d. A case of 
grade 4, life-threatening thrombocytopenia assessed as possibly related to ulixertinib 
as well as to underlying Noonan Syndrome was reported in a 23-year-old woman. 
In order to monitor for potential hematologic toxicity in humans, routine clinical 
laboratory hematology tests, should be performed and any indication of abnormalities 
may result in further investigations. 
Phototoxicity 
Ulixertinib exhibits an absorbance peak in the range of UV-A/UV-B light, specifically 
at ~320 nm. In clinical studies with ulixertinib to date, 5 TEAEs of photosensitivity 
reaction in patients on 75mg (1 patient) and 600mg b.i.d. (4 patients) have been 
reported (all in study BVD-523-01). 
Beyond dermatological monitoring (above), potential risks of direct phototoxic 
reactions induced by ulixertinib should be further minimized by advising patients to 
minimize sun exposure, use broad-spectrum sunscreens, and wear sunglasses.  
Patients will be informed that relevant sun exposure may occur even through glass, 
such as while driving. 
Ophthalmological Effects 
While the preclinical toxicology studies of ulixertinib have not revealed any exposure-
dependent ophthalmological toxicities, based on clinical studies of MEK1/2 inhibitors 
which highlighted ocular toxicities that may reflect mechanistically attributable risks 
observable in a proportion of patients, clinical studies of ulixertinib have included close 
monitoring for ocular toxicities. In the clinical trials to date, the following ocular events 
have been rarely reported (n=115): visual impairment (7%), vision blurred (4%), 
photophobia (2%), retinal vein occlusion (<1%, reversible grade 3), vitreous floaters 
(<1%), chorioretinopathy (<1%), halo vision (<1%), and retinal detachment (<1%). 
Although it is not definitively understood whether ocular toxicities reflect primary 
pharmacology associated with global inhibition of the MAPK pathway, specific 


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management and exclusion criteria will be defined in this study protocol as the 
toxicities could potentially severely and irreversibly impact patient well-being. 
Cardiac Effects 
The balance of preclinical evidence suggests ulixertinib has low, but observable, 
potential to cause QT prolongation.  In study BVD-523-01, 105 patients (24 patients 
in Part 1 and 81 patients in Part 2) were included in an analysis of QT prolongation. 
Electrocardiograms extracted from 12-lead Holter monitors, along with time matched 
pharmacokinetic blood samples, were collected over 12 hours on cycle 1, day 1 and 
cycle 1, day 15 and analyzed by a core ECG laboratory. The estimated mean changes 
from the baseline in the study-specific QTc interval, at the ulixertinib Cmax, were – 
0.529 msec (90% confidence interval [CI] – 6.621, 5.562) on day 1 and – 9.202 msec 
(90% CI – 22.505, 4.101) on day 15, well below the 20 msec threshold considered 
appropriate for oncology agents. Overall, the evaluated ECG data showed that 
ulixertinib does not prolong the corrected QT interval using the Fridericia formula 
(QTcF) interval in patients in a concentration-dependent manner; ulixertinib may 
modestly increase the heart rate to a degree not likely to be of clinical significance for 
patients without underlying significant cardiovascular conditions (Mendzelevski et al, 
2018).  
TEAEs in the System Organ Class of cardiac disorders have been reported in 
approximately 14% of the patients treated to date, with preferred terms including 
tachycardia, atrial fibrillation, and palpitations. One case of cardiac failure was 
considered at least possibly related to ulixertinib. Patients dosed with ulixertinib 
undergo assessment of cardiac status (LVEF and ECG) at baseline and subsequently 
as needed. 
Tissue Mineralization 
Dose-dependent tissue mineralization in association with an increase in serum 
phosphorus and a modest decrease in serum calcium was observed in rodent 
toxicology studies of ulixertinib. Furthermore, tissue mineralization has been reported 
in rodents with other compounds that target the MAPK pathway and published studies 
suggest that the MAPK pathway is a negative regulator of matrix mineralization both 
in vitro and in vivo. 
Routine clinical laboratory tests that may indicate shifts in mineralization of the bone 
and tissues, including blood chemistry analyses for calcium and inorganic phosphate, 
are performed in the clinical program and any indication of abnormalities may result 
in further investigations. TEAEs of hypocalcemia and increased blood phosphorus 
have been reported; however, tissue mineralization has not been reported. 


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4.2.2 
Pharmacology Studies 
In this section a short summary of preclinical data is provided. Detailed information is 
presented in the current ulixertinib (BVD-523) Investigator’s Brochure and Germann 
et al, 2017.  
The observation that ulixertinib’s cellular potency is associated with MAPK pathway 
alterations, which are characterized by ERK activity and dependency, was confirmed 
and extended with the use of murine xenograft models. Ulixertinib has demonstrated 
dose-dependent efficacy in human mouse xenograft models, which harbor alterations 
within the MAPK pathway. This includes BRAF (V600E) cell line xenograft models 
A375 (melanoma) and colo205 (colon), and KRAS (G12C) mutant model MIAPaca2 
(pancreas). In addition, ulixertinib activity has also been demonstrated in a patient 
derived xenograft melanoma model established from the tumor of an individual 
relapsing off BRAF targeted therapy with vemurafenib. Furthermore, ulixertinib 
displayed impressive activity when used in combination with BRAF inhibitor 
dabrafenib (Germann et al, 2017).  
4.2.2.1 
Single Agent Ulixertinib is Efficacious in a Mouse Xenograft 
Model of BRAF Mutant Human Melanoma Cell Line (A375) 
In A375 cell line xenografts, 5, 25, 50, and 100 mg/kg twice daily doses of ulixertinib 
were compared following 18 days of treatment. For all doses, no significant body 
weight changes were observed. Ulixertinib demonstrated significant dose-dependent 
antitumor activity starting at 50 mg/kg twice daily (Figure 4.1). Doses of 50 and 100 
mg/kg twice daily significantly attenuated tumor growth, with tumor growth inhibition 
(TGI) of 71% (P = 0.004) and 99% (P < 0.001), respectively. Seven partial responses 
(PR) were noted in the 100 mg/kg twice daily group; no regression responses were 
noted in any other group. 
 
 
 
 
 
 
 
 


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Figure 4.1 
BVD-523 Displays Dose Dependent Efficacy in the Murine 
Xenograft Model of Human BRAF-Mutant Melanoma Cell Line 
A375 
 
4.2.2.2 
Ulixertinib Demonstrates Profound Anti-Tumor Activity when 
Combined with Dabrafenib in Mouse Xenograft Model of 
BRAF Mutant Human Melanoma Cell Line (A375) 
To evaluate the benefit of the combination, efficacy was assessed in vivo utilizing 
xenografts of the BRAF (V600E) mutant human melanoma cell line A375. Because of 
the response of combined dabrafenib and ulixertinib treatment, dosing in the 
combination groups was stopped on day 20 to monitor for tumor regrowth and was 
reinitiated on day 42 (Figure 4.2). Tumors were measured twice weekly until the study 
was terminated on day 45. The median time to endpoint (TTE) for controls was 9.2 
days, and the maximum possible tumor growth delay (TGD) of 35.8 days (end of 
study) was defined as 100%. Temozolomide treatment resulted in a TGD of 1.3 days 
(4%) and no regressions. The 50- and 100-mg/kg dabrafenib monotherapies produced 
TGDs of 6.9 days (19%) and 19.3 days (54%), respectively, a significant survival 
benefit (P < 0.001), and 1 PR in the 100 mg/kg group. The 100-mg/kg ulixertinib 
monotherapy resulted in a TGD of 9.3 days (26%), a significant survival benefit (P 
< 0.001), and 2 durable complete responses (CRs). The combinations of dabrafenib 
with ulixertinib each produced the maximum possible 100% TGD with statistically 
superior OS compared with their corresponding monotherapies (P < 0.001). The 
lowest dose combination produced a noteworthy 7/15 tumor-free survivors (TFS), and 
the 3 higher dosage combinations produced a total of 43/44 TFS, consistent with 
curative or near-curative activity observed in the Kaplan-Meyer plot ( 
Figure 4.3).  
0
4
8
12
16
20
0
500
1000
1500
2000
2500
3000
3500
Time (Day)
Tumor Volume (mm3) 
Vehicle
BVD-523 (5 mg/kg, po, BID)
BVD-523 (25 mg/kg, po, BID)
BVD-523 (50 mg/kg, po, BID)
BVD-523 (100 mg/kg, po, BID)


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Figure 4.2 
Mean Tumor Volume Plot; BVD-523 and Dabrafenib Combination 
Demonstrates Superior Efficacy Compared to Either Single Agent 
Alone in the A375 BRAF Mutant Melanoma Xenograft Model 
 
 
Figure 4.3 
Kaplan-Meyer Plot; BVD-523 and Dabrafenib Combination 
Demonstrates Superior Survival Compared to Either Single Agent 
Alone in the A375 BRAF Mutant Melanoma Xenograft Model 
 
 
 


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4.2.3 
Toxicity and Safety Studies 
When ulixertinib was characterized using in vitro screens against 66 receptors and ion 
channels, no toxicologically significant interactions were identified. Additionally, 
ulixertinib was negative in bacterial mutation and in vivo micronucleus screening 
assays; therefore, ulixertinib is not considered to have a significant genetic toxicology 
risk. 
While ulixertinib modestly inhibits the human ether-a-go-go related gene (hERG) 
current (IC50 3.4 µM), no significant effects were seen in action potentials recorded 
from dog Purkinje fibers exposed to up to 10 μg/mL and no significant cardiovascular 
findings were observed upon acute oral dosing of the compound at dose levels up to 
50 mg/kg in dogs (Cmax = 17.3 µM). Thus, ulixertinib is considered to have a low 
potential to cause QT prolongation in patients, but, as stated, patients dosed with 
ulixertinib in the first-in-human study, BVD-523-01, were monitored for potential QTc 
prolongation and related cardiotoxicities via Holter monitoring. No clinically significant 
cardiac abnormalities have been seen in the ulixertinib clinical program to date.  
In vitro studies suggest that the compound is metabolized primarily via oxidation by 
multiple CYPs including 3A4, 2D6, and 1A2. No significant CYP induction was 
observed after up to 14 days drug treatment in rats. In vitro human liver microsome 
studies do demonstrate ulixertinib to induce CYP1A2, CYP2B6, and CYP3A4 mRNA 
expression, whist also directly inhibiting CYP2C8 and CYP3A4/5. These data suggest 
a limited potential for drug-drug interactions. 
Ulixertinib HCl salt is orally available in multiple species (absolute bioavailability 
%F = 23% in dog to 100 % in monkey) when formulated as a simple suspension in 
1% carboxymethyl-cellulose (CMC) and has a half-life of 2-4 hours across all species. 
Ulixertinib was administered to male and female Sprague-Dawley rats in several 
toxicology studies: (1) a GLP study for up to 28 days at dose levels up to 50 mg/kg/day 
twice daily; (2) for up to 14 days at dose levels up to 100 mg/kg twice daily; and (3) for 
up to 5 days at dose levels up to 150 mg/kg/dose once daily. The incidence and 
severity of mineralization seen in these studies was dose-dependent and effects were 
observed in one or more tissues at toxic doses. In animals in which mineralization 
occurred after treatment with ulixertinib, significantly increased serum phosphorus and 
modestly decreased serum calcium were seen. These effects were not observed in 
animals in which there was no mineralization. Therefore, the risk of tissue 
mineralization can be assessed by serum phosphorus and calcium monitoring. A 
clinical monitoring strategy similar to this was previously employed for related drugs 
that target the MAPK pathway because those compounds likewise elicited 
mineralization in rodents. 


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When ulixertinib was administered to male and female Sprague-Dawley rats for up to 
28 days at a dose level of 25 or 50 mg/kg twice daily, ulixertinib was poorly tolerated.  
Although most clinical signs and clinical pathology findings reversed following 4 weeks 
of recovery, skin lesions and histopathology findings persisted in many tissues at both 
dose levels after the recovery. Based on these findings, 25 and 50 mg/kg twice daily 
dose levels were considered severely toxic. Administration of 12.5 mg/kg twice daily 
for 28 days was generally well-tolerated by rats of both sexes; however, this dose level 
was associated with test article-related findings that included (1) swelling in the neck, 
(2) decreased forelimb strength, (3) multiple clinical pathology findings, and (4) 
enlarged lymph nodes, spleen, and mammary gland. Based on these observations, 
the severely toxic dose in 10% of the animals (STD10) for ulixertinib when administered 
for up to 28 days in Sprague-Dawley rats is 12.5 mg/kg given twice daily (25 
mg/kg/day). On Day 28 of the dosing phase, this dose level corresponded with a Cmax 
of 28700 and 15323 ng/mL and AUC0-12 of 264868 and 124341 hr.ng/mL for males 
and females, respectively. 
Ulixertinib was administered to male and female beagle dogs for up to 28 days at dose 
levels of 15, 5, or 2 mg/kg twice daily. Initial analysis of the toxicity profile observed 
shows that ulixertinib was well tolerated in dogs. The rat was designated the most 
sensitive species and rat data were used to calculate the starting dose in man. 
Based on the data accumulated to date, ulixertinib possesses a toxicology profile 
which presents no impediment to its development as an anti-cancer agent. 
4.2.4 
Previous Human Experience 
Ulixertinib has been administered to humans in 5 commercially sponsored clinical 
studies, 4 investigator sponsored trials (IST), and 3 NCI sponsored trials to date: 


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Table 4.1 
Previous Human Experience with Ulixertinib 
Study Type 
Study Identifiers 
Status/Results 
Commercial 
sponsored 
NCT01781429  
BVD-523-01 
Phase 1 Dose-
Escalation, Safety, 
Pharmacokinetic and 
Pharmacodynamic 
Study of BVD-523 in 
Patients with Advanced 
Malignancies.  
In the first in human, phase I study of ulixertinib a total of 135 patients 
were enrolled in the dose escalation and dose expansion phases of 
the study. Twenty-seven patients were enrolled in the dose escalation 
phase (10-900 mg b.i.d.). The maximum tolerated dose (MTD) and 
recommended phase 2 dose (RP2D) was determined to be 600 mg 
twice daily given continuously. Dose-limiting toxicities (DLT) included 
rash, diarrhea, elevated AST, and elevated creatinine. Drug exposure 
was dose proportional up to the RP2D, which provided near-complete 
inhibition of ERK activity in whole blood. In the expansion cohort (108 
patients), there were no drug related deaths; however, 32% of patients 
required a dose reduction. The most common AEs at RP2D, 
regardless of attribution, were diarrhea (50%), fatigue (50%), nausea 
(45%), decreased appetite (31%), and dermatitis acneiform (31%). In 
addition to 3 patients with partial responses during escalation (11%), 
an additional 11 of 81 (14%) evaluable patients at expansion had a 
partial response: 1 BRAFV600E mutant melanoma patient refractory to 
prior BRAF/MEK inhibitor treatment, 3 NRAS mutant melanoma 
patients, 3 patients with BRAF mutant lung cancers including response 
in brain metastases, 1 with BRAFV600E mutant glioblastoma multiforme, 
1 with BRAFG469A head & neck cancer, 1 with BRAFG469A small-bowel 
cancer, and 1 with BRAFL485W gallbladder cancer. The duration of 
response ranged from 2 to 24+ months (82, 98). A total of 28 
evaluable patients whose BRAF mutations were not at amino acid 
V600 were included in the BVD-523-01 solid tumor study of ulixertinib.  
Figure 4.4 and 4.5 provide the percent target lesion change and study 
duration for patients with atypical BRAF alterations, respectively. 


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Study Type 
Study Identifiers 
Status/Results 
Commercial 
sponsored 
NCT02296242 
BVD-523-02  
Phase 1/2 Dose-
Escalation, Safety, 
Clinical Activity, 
Pharmacokinetic and 
Pharmacodynamic 
Study of the ERK 1/2 
Inhibitor BVD-523 in 
Patients with Acute 
Myelogenous 
Leukemia or 
Myelodysplastic 
Syndromes 
An open-label, multi-center Phase I/II study to determine the safety, 
tolerability, and pharmacokinetic profile of ulixertinib in patients with 
AML or MDS, as well as to assess clinical response, PFS, and 
duration of response in those patients. The study consisted of 2 parts: 
Part 1 was a dose-escalation phase to investigate safety and 
determine the MTD and the RP2D, and Part 2 was a cohort-expansion 
phase using the RP2D to examine safety, and to identify early 
indications of clinical effects. Patients received continuous twice-daily 
oral dosing with ulixertinib in 21-day cycles. A total of 18 patients 
received at least one dose of ulixertinib in the dose-escalation phase 
(300-750mg b.i.d.). In Part 1, the MTD and RP2D were determined to 
be 600 mg b.i.d., and this is the dose that was tested in the cohort-
expansion phase (Part 2) of the study. A total of 35 patients received 
at least one dose of ulixertinib in the cohort-expansion phase of the 
study. Of the 35 patients in Part 2, 14 patients (40%) were RAS 
mutant positive and 21 patients (60%) were RAS mutant negative. The 
most frequently reported study drug-related events at RP2D were 
diarrhea (31%), nausea (20%), increased creatinine (17%), vomiting 
(9%), and rash (5%). All bone marrow biopsies in Part 1 showed less 
than partial response. In Part 2, one patient with RAS (+) AML, had 
CRp at two sequential visits. A second patient with RAS (-) AML, had 
a CR on Cycle 2, Day 1. All other evaluations in Part 2 AML patients 
showed less than PR. A third patient with RAS (+) MDS had a PR on 
Cycle 2, Day 1. All other bone marrow evaluations in Part 2 MDS 
patients showed less than PR. 
Commercial 
sponsored 
NCT02994732 
BVD-523HV001: 
A Phase 1 Study to 
Investigate the 
Absorption, 
Metabolism, and 
Excretion of [14C]BVD-
523 Following Single 
Oral Dose 
Administration in 
Healthy Male Subjects 
The purpose of study BVD-523HV001 was to evaluate the absorption 
and excretion characteristics as well as relevant pharmacokinetic 
properties of ulixertinib; and to characterize and, where possible, 
identify the metabolites present in plasma, urine, and feces in healthy 
male subjects following a single dose of 600mg (approximately 200 
μCi) of [14C]-ulixertinib. The secondary objective of this study was to 
evaluate the safety and tolerability of a single oral dose of [14C]-
labeled ulixertinib in healthy male subjects. A total of 6 subjects were 
enrolled. The absorption of ulixertinib (BVD-523) was moderate and 
after reaching Cmax, concentrations of ulixertinib (BVD-523) in plasma 
appeared to decline in a generally biphasic manner. Ulixertinib (BVD-
523) undergoes moderate metabolism to produce 13 
identified/characterized metabolites in plasma and excreta. The 
metabolites BVD-502+BVD503 and BVD-513 were formed moderately 
rapidly and their plasma concentration-time profiles generally mirrored 
that of parent drug, suggesting formation rate limited elimination. The 
metabolite BVD-506 was found to be present and disproportionate 
levels compared to levels measured in pre-clinical in vivo studies. The 
primary route of elimination was through fecal excretion. No clinically 
significant findings with respect to clinical laboratory, vital signs, ECG, 
or physical examinations. Fatigue and diarrhea were reported for 2 
subjects (33%) and were possibly related to study drug. All TEAEs 
were of mild severity and there were no moderate or severe events 
reported. 


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Study Type 
Study Identifiers 
Status/Results 
Commercial 
sponsored 
BVD-523A-FE 
A Randomized, Open-
Label, Single-Dose, 2-
Way Crossover Study 
to Evaluate the Effect 
of Food on the 
Pharmacokinetics, 
Safety and Tolerability 
of Orally Administered 
BVD-523 in Healthy 
Volunteers 
A Phase I, randomized, open-label, single-dose, 2-way crossover 
study to assess the safety and PK in 14 healthy male and female 
subjects. Subjects received a single oral dose of BVD-523A (an 
investigational formulated blend of ulixertinib) in 2 different treatment 
periods; once after an overnight fast of at least 10 hours and once 
after consumption of a FDA-defined high-fat breakfast. There was a 
washout period of 5 days between dosing in one period and dosing in 
the next period. Subjects were randomized equally to receive 1 of 2 
treatments sequences (fasted/fed or fed/fasted), with 7 subjects 
assigned to each sequence. Each subject received both treatments. 
PK concentrations achieved in the fed group were considerably higher 
than observed in the fasted group. However, fasting and fed conditions 
were extreme. Collective experience in patients and healthy volunteers 
shows that best exposure and variability is achieved when ulixertinib is 
taken with food. There were no clinically significant findings with 
respect to clinical laboratory, vital signs, ECG, or physical 
examination. Headache in 2 subjects (14%) under fed conditions and 
diarrhea in 1 subject (7%) under fasted conditions were considered by 
the investigators to be possibly related to the study drug. All TEAEs 
were of mild severity, and there were no moderate or severe events 
reported. 
Commercial 
sponsored 
BVD-523-FC 
A Randomized, Open-
Label, Single-Dose, 2-
Way Crossover Study 
Evaluating the 
Pharmacokinetics, 
Safety, and Tolerability 
of two oral formulations 
of Ulixertinib (BVD-523) 
in Healthy Volunteers 
A Phase I, randomized, open-label, single-dose, 2-way crossover 
study to assess the effect of two oral formulations of ulixertinib on the 
PK, safety, and tolerability of a single oral dose of 600mg ulixertinib in 
14 healthy male and female subjects. The oral formulations included a 
single dose of 600mg powder in capsule (PIC) formulation and a 
single oral dose of 600mg formulated blend formulation of ulixertinib. 
Subjects were randomized equally to receive 1 of the 2 treatment 
sequences with 7 subjects assigned to each sequence and a washout 
period of 5 days separated the treatments. The formulated blend 
formulation produced peak and total systemic exposures which were 
slightly lower than PIC formulation. Additionally, the AUClast and AUCinf 
of the formulated blend formulation were approximately 25% lower 
than compared to PIC formulation. No clinically significant findings with 
respect to clinical laboratory, vital signs, ECGs, or physical 
examinations. Headaches were reported in 4 subjects (29%) and were 
possibly related to study drug. All other possibly related TEAEs were 
only reported by 1 subject (7%). All events were of mild severity, 
except for 1 event of urticaria, which was of moderate severity. 
Investigator 
sponsored 
NCT02608229 
Phase Ib Study of 
BVD-523 Plus Nab-
Paclitaxel and 
Gemcitabine in 
Patients with 
Metastatic Pancreatic 
Cancer 
Study was stopped after part 1 (dose escalation) due to tolerability 
issues experienced from the triple combination treatment. 


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Study Type 
Study Identifiers 
Status/Results 
Investigator 
sponsored 
NCT03454035 
A Phase I Trial of 
Ulixertinib (BVD-523) 
in Combination with 
Palbociclib in Patients 
with Advanced Solid 
Tumors with 
Expansion Cohort in 
Previously Treated 
Metastatic Pancreatic 
Cancer 
Ongoing 
Investigator 
sponsored 
NCT04145297 
Phase 1 study of 
ulixertinib and 
hydroxychloroquine in 
patients with 
advanced MAPK-
mutated 
gastrointestinal 
adenocarcinomas 
Ongoing 
Investigator 
sponsored 
NCT03417739 
A Phase II Study of 
BVD-523 in Metastatic 
Uveal Melanoma 
In interim analysis of 13 patients, four patients had best response of 
SD (31%), seven had best response of progressive disease (54%), 
and two were unevaluable for response (15%). According to the Simon 
design, the trial stopped recruitment at this point due to lack of 
responders in the first stage. 
NCI 
sponsored 
NCT03155620 
Targeted Therapy 
Directed by Genetic 
Testing in Treating 
Pediatric Patients with 
Relapsed or 
Refractory Advanced 
Solid Tumors, Non-
Hodgkin Lymphomas, 
or Histiocytic 
Disorders (The 
Pediatric MATCH 
Screening Trial) 
Ongoing 
 
NCI 
sponsored 
NCT02465060 
Targeted Therapy 
Directed by Genetic 
Testing in Treating 
Patients with 
Advanced Refractory 
Solid Tumors, 
Lymphomas, or 
Multiple Myeloma (The 
MATCH Screening 
Trial) 
Ongoing 


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Study Type 
Study Identifiers 
Status/Results 
NCI 
sponsored 
NCT03698994 
Ulixertinib in Treating 
Patients with 
Advanced Solid 
Tumors, Non-Hodgkin 
Lymphoma, or 
Histiocytic Disorders 
With MAPK Pathway 
Mutations (A Pediatric 
MATCH Treatment 
Trial) 
Ongoing 
 
Figure 4.4 
Percent Target Lesion Change in Patients from BVD-523-01 with 
BRAF non-V600 mutations 
 
 
 
 


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Figure 4.5 
Study Durations of Patients from BVD-523-01 with BRAF non-
V600 mutations 
 
 
Based on these data it was concluded that ulixertinib at 600mg twice a day has an 
acceptable safety profile and has produced durable responses in patients with NRAS 
mutant melanoma, BRAF V600 and non-V600 mutant solid tumors including 
melanoma, glioblastoma multiforme, gallbladder, head and neck cancers, and lung 
cancers and exhibits clear CNS activity. Ulixertinib also resulted in durable responses 
in patients who progressed on prior BRAF +/- MEK inhibitor treatment or who were 
treatment naïve.  
 


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5 
OBJECTIVES AND ENDPOINTS 
5.1 
PART A – TUMOR HISTOLOGY AGNOSTIC 
5.1.1 
Primary Objective 
To assess the clinical benefit of ulixertinib as measured by the ORR in patients 
receiving ulixertinib that have advanced malignancies harboring a MEK or atypical 
BRAF alteration. 
Primary Endpoint(s): ORR will be defined as the percentage of patients achieving a 
Best Overall Response (BOR) of confirmed Complete Response (CR) and/or Partial 
Response (PR), according to RECIST 1.1. 
5.1.2 
Secondary Objectives 
The secondary objectives are: 
• To evaluate the safety profile of ulixertinib 
• To assess the DOR 
• To assess the PFS and OS over 18 months 
• To measure the blood levels of ulixertinib and selected metabolites 
 
Secondary Endpoint(s):  
• Safety profile, including term, incidence, severity, and duration of AEs, as per 
CTCAE v5.0 
• DOR according to RECIST 1.1 
• PFS time according to RECIST 1.1 
• OS time 
• Pharmacokinetic profile of ulixertinib (BVD-523) and selected metabolites 
5.1.3 
Exploratory Objectives 
To evaluate the effects of ulixertinib on pharmacodynamic markers. 
 
Exploratory Endpoint(s):  
• ctDNA, tissue biopsies, and/or blood to access biomarkers. Assays include, 
but are not limited to, phosphorylation of RSK from whole blood, RPPA to 
assess protein levels, e.g. DUSP 4/6, plus Nanostring and/or RNA-exome to 
asses mRNA expression in tissue pre- and post-ulixertinib treatment. 
 


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5.2 
PART B – TUMOR HISTOLOGY SPECIFIC 
5.2.1 
Primary Objective 
To assess PFS in patients receiving ulixertinib in defined tumor histologies (up to three 
histologies to be selected) compared to physician’s choice of treatment. Patient’s 
tumors must harbor a specified MEK or atypical BRAF alteration. 
Primary Endpoint(s): PFS will be defined as the time from first day of trial medication 
to disease progression according to RECIST 1.1, or death. 
5.2.2 
Secondary Objectives 
The secondary objectives are: 
• To evaluate the safety profile of ulixertinib 
• To assess OS over 18 months in patients receiving ulixertinib with a defined 
tumor histology and specified MEK or atypical BRAF alteration, compared to 
physician’s choice of treatment 
• To determine the ORR and DOR in patients receiving ulixertinib with a defined 
tumor histology and a MEK or atypical BRAF alteration, according to RECIST 
1.1, compared to physician’s choice of treatment 
 
Secondary Endpoint(s):  
• Safety profile, including term, incidence, severity, and duration of AEs, as per 
CTCAE v5.0 
• OS time 
• ORR and DOR according to RECIST 1.1 


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6 
STUDY DESIGN 
6.1 
OVERALL DESIGN 
BVD-523-ABC is a two-part, phase II, multicenter study of the ERK inhibitor ulixertinib 
(BVD-523) with an open-label, tumor histology agnostic part (Part A) and a tumor 
histology specific part (Part B). 
6.1.1 
Part A: Tumor Histology Agnostic 
Part A will include six groups of patients with advanced malignancies. Group 1 will 
include patients with advanced malignancies, other than CRC, having a BRAF 
alteration that results in an amino acid change at position G469, L485, or L597. Group 
2 will include patients with advanced malignancies, other than CRC, having a specified 
Class 2 BRAF alteration (see Appendix 2). Group 3 will include patients with advanced 
malignancies, other than CRC, having any atypical BRAF alteration that is not 
specified in Group 1 or 2. Group 4 will include patients with CRC having any activating 
atypical BRAF alteration. Group 5 will include patients with tumors, other than CRC, 
harboring alterations in MEK1/2. Group 6 will include patients with CRC harboring 
alterations in MEK1/2. 
Ongoing data from Part A will be used, in part, to prioritize one or more tumor 
histologies that warrant study in Part B.  
6.1.2 
Part B: Tumor Histology Specific 
Part B will randomly enroll patients with one of up to three specified tumor histologies 
to receive either ulixertinib or the physician’s choice of treatment in a 2:1 ratio. 
Physician’s choice will be restricted to two approved (not off-label) treatments for each 
tumor histology (agents targeting BRAF or MEK kinases and experimental agents are 
not permitted as physician’s choice). Tumors must harbor either a MEK or atypical 
BRAF alteration. The specific histology/histologies and alterations to be included in 
this part will be selected based on available data from Part A and discussion with the 
clinical investigators, the medical monitor, and the sponsor. 
The randomization information can be found in Section 8.3. In Part B, if a patient 
progresses on the physician’s choice of treatment, then they may crossover to the 
ulixertinib arm. 
6.2 
JUSTIFICATION FOR DOSE 
Based on the experience of the studies BVD-523-01 and BVD-523-02, 600 mg b.i.d. 
taken orally will be the starting dose for all patients initiating therapy with ulixertinib as 
a single agent. 


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6.3 
NUMBER OF PATIENTS 
Total enrollment for Part A is targeted at approximately 228 patients with 38 patients 
per group. Additional patients may be enrolled as appropriate. 
Total enrollment for Part B is targeted to approximately 80-100 patients per histology 
with up to three histologies included, however, additional patients may be enrolled.  
6.4 
NUMBER OF STUDY SITES 
The study will take place at sites within the United States. Approximately, up to 25 
sites will be utilized, however, because the patient population is relatively rare, clinical 
sites may need to be added as qualifying patients are found. Clinical trial networks 
may be utilized. Each study site may enroll as many eligible patients as possible due 
to the relatively rare patient population. 
6.5 
STUDY DURATION AND END OF STUDY DEFINITION 
The estimated duration of accrual is 21 months. The total duration of the study will be 
approximately 38 months. 
A patient is considered to have completed the study if they have completed all phases 
of the study including the last visit or the last scheduled procedure shown in the SoA.  
The end of the study is defined as completion of the last visit or procedure shown in 
the SoA in the trial globally. 


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7 
STUDY POPULATION 
7.1 
INCLUSION CRITERIA 
Patients must meet all of the inclusion criteria to be eligible: 
1. Patients with a locally advanced or metastatic malignancy, that has progressed 
following systemic therapy for their disease, if available, or for which the patient 
is not a candidate or refuses. 
2. Tumor harboring a MEK or atypical BRAF alteration.  
3. Provided signed and dated informed consent prior to initiation of any study-related 
procedures that are not considered standard of care (SoC). 
4. Male or female patients aged ≥18 years. 
5. Patients must have measurable disease by RECIST version 1.1. 
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2. 
7. Adequate renal function (using Cockcroft-Gault) [creatinine ≤1.5 times ULN 
(upper limit of normal)] or a glomerular filtration rate (GFR) of ≥50 mL/min. 
8. Adequate hepatic function [total bilirubin ≤1.5 times ULN; AST (aspartate 
transaminase) and ALT (alanine transaminase) ≤3 times ULN or ≤5 times ULN if 
due to liver involvement by tumor]. 
9. Adequate bone marrow function (hemoglobin ≥9.0 g/dL; platelets ≥100 x 109 
cells/L; absolute neutrophil count ≥1.5 x 109 cells/L). 
10. Adequate cardiac function:  
• Left ventricular ejection fraction (LVEF) of >50% as assessed by multi-gated 
acquisition (MUGA) or ultrasound/echocardiography (ECHO); and  
• A corrected QT interval (QTc) <480ms by the Fridericia method (QTcF). 
11. Contraception:  
a. For women: Negative pregnancy test for females of child-bearing potential; 
must be surgically sterile, postmenopausal (no menstrual cycle for at least 
12 consecutive months), or compliant with a medically approved 
contraceptive regimen during and for 3 months after the treatment period. 
Abstinence is not considered an adequate contraceptive regimen.  
b. For men: Must be surgically sterile, or compliant with a medically approved 
contraceptive regimen during and for 3 months after the treatment period.  


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12. Willing and able to participate in the trial and comply with all trial requirements. 
13. Patients with a prior or concurrent malignancy whose natural history or treatment 
does not have the potential to interfere with the safety or efficacy assessment of 
the investigational agent may be included after consultation with the medical 
monitor. 
  
7.2 
EXCLUSION CRITERIA 
Patients who fulfill one or more of the following criteria will not be eligible for inclusion in 
this trial: 
1. Gastrointestinal (GI) condition that could impair absorption of study medication 
(specific cases e.g., remote history of GI surgery, may be enrolled after 
discussion with the medical monitor) or inability to ingest study medication. 
2. Uncontrolled or severe intercurrent medical condition. 
3. Known uncontrolled brain metastases. Stable brain metastases either treated or 
being treated with a stable dose of steroids/anticonvulsants, with no dose change 
in the previous 4 weeks, can be allowed. 
4. Having received any cancer-directed therapy (chemotherapy, hormonal therapy, 
biologic or immunotherapy, etc.) within 28 days or 5 half-lives (whichever is 
shorter) prior to the first dose of study drug. Patients previously treated with 
radiotherapy must have recovered from the acute toxicities associated with such 
treatment. 
5. Major surgery within 4 weeks prior to first dose. 
6. Any use of an investigational drug within 28 days or 5 half-lives (whichever is 
shorter) prior to the first dose of study drug. A minimum of 10 days between 
termination of the investigational drug and administration of study drug is 
required. In addition, any drug-related toxicity except alopecia should have 
recovered to Grade 1 or less. 
7. Prior therapy with any ERK inhibitor (e.g. LY3214996, LTT462).   
8. Groups 1-4: Prior therapy with any BRAF and/or MEK inhibitor (e.g. encorafenib, 
dabrafenib, vemurafenib, binimetinib, trametinib, cobimetinib) is excluded. Prior 
BRAF and/or MEK inhibitor therapy is permitted for Groups 5 and 6. 
9. For Part B, agents targeting BRAF or MEK kinases and experimental agents are 
not permitted as physician choice.  
10. Pregnant or breast-feeding women. 


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11. Any evidence of serious active infections. Patients are allowed to enroll if they 
have been fever-free for at least 48 hours and are on an active treatment that is 
not prohibited in Appendix 1. 
12. Any important medical illness or abnormal laboratory finding that would increase 
the risk of participating in this study (based on the investigator’s judgment).  
13. A history or current evidence/risk of retinal vein occlusion (RVO) or central serous 
retinopathy (CSR). 
14. Concurrent therapy with any other investigational agent. 
15. Concurrent therapy with drugs known to be strong inhibitors or inducers of 
CYP1A2, CYP2D6, and CYP3A4.  
7.3 
SCREEN FAILURES 
Screen failures are defined as patients who consent to participate in the clinical trial but 
who do not meet one or more criteria required for participation in the trial during the 
screening procedures. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure patients, to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from 
regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any serious adverse event (SAE). 
Individuals who do not meet the criteria for participation in this trial (screen failure) may 
be rescreened (up to a maximum of 1 time for the same individual). Rescreened patients 
will be assigned a new subject identification number. Labs can be retested within the 
screening window and not count as a rescreen. 
7.4 
STRATEGIES FOR RECRUITMENT AND RETENTION 
Potential patients will be identified by investigators in the setting of their clinics. Potential 
patients may also be identified by Strata Oncology through their Strata Precision 
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8 
STUDY DRUG 
8.1 
STUDY DRUG(S) ADMINISTRATION 
8.1.1 
Study Drug Description 
Ulixertinib (BVD-523) is a novel, reversible, ATP-competitive small molecule that 
potently inhibits both ERK1 and ERK2 protein kinases in the sub-nanomolar range, 
while not significantly inhibiting any of an array of kinases even at 1000-fold greater 
concentrations (Germann et al, 2017).   
More information is available in the Investigator’s Brochure for ulixertinib. 
8.1.2 
Dosing and Administration 
Patients will initially receive 600 mg oral doses of the formulated blend formulation of 
ulixertinib. Ulixertinib is to be taken twice daily (b.i.d.) orally with at least 8 ounces of 
water for 28 days (a “Cycle”), at 12-hour ± 2 hour intervals. The study drug should be 
taken at approximately the same time each day with food. A patient that is observed 
to vomit an intact capsule after dosing in the clinic during the PK measurements may 
receive a substitute dose of drug. However, patients should be instructed NOT to take 
a substitute capsule if vomiting occurs after self-dosing at home. Missed doses should 
be skipped and not taken as a double dose at the next dosing timepoint.  
Patients will be provided enough ulixertinib for a full cycle to self-administer at home. 
8.1.3 
Dose Interruptions and Adjustments 
Patients experiencing unacceptable toxicity will have their treatment interrupted until 
the toxicity returns to ≤ Grade 1 or pre-treatment baseline (whichever is more severe).  
Resumption of ulixertinib may occur at a lower dose level, aligning with capsule dose 
availability. Such dose adjustments will be done in consultation with the investigators 
and medical monitor of the study. 
If a non-treatment related AE or toxicity-related dose delay lasts for > 21 days, 
treatment will be discontinued permanently, and the patient should be removed from 
study treatment. 
8.2 
ACCOUNTABILITY/APPEARANCE/STORAGE 
8.2.1 
Acquisition and Accountability 
Dispensing instruction will be provided in the Pharmacy Manual. 
The investigator or study staff will verify the integrity of the clinical trial supplies 
(storage conditions, correct amount received, condition of shipment, kit numbers, etc.) 
according to their Standard Operating Procedures (SOP). 


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The following data will be tracked on the drug accountability log provided by the 
sponsor, and recorded in the eCRF: 
• Date received 
• Lot number 
• Date dispensed 
• Patient number 
Records of study medication (used, lost, destroyed, and returned containers, 
individual capsules) should be made at each patient visit in the eCRF. Drug 
accountability and reconciliation will be checked by the site study monitor during site 
visits and at completion of study treatment. 
Unless prohibited by investigational site’s SOP, used study medication is to be 
retained until the monitor has verified drug accountability. Once the site monitor has 
verified drug accountability at the site, any drug remaining in opened dispensing 
containers will be destroyed. Unused and unopened study medication will be returned 
to the sponsor. 
8.2.2 
Formulation, Appearance, Packaging, and Labeling 
Ulixertinib 
drug 
substance 
is 
manufactured 
according 
to 
cGMP 
as 
a 
mono-hydrochloride salt and is supplied as a formulated powder blend comprised of 
standard excipients to support the manufacturing processes that is encapsulated in a 
hard gelatin capsule. Capsules (white) contain 150 mg of ulixertinib calculated on free 
base content and are packaged in white high-density polyethylene (HDPE) bottles.  
8.2.3 
Product Storage and Stability 
Information will be provided in the study manual. 
8.3 
RANDOMIZATION 
Part A is designed as an open-label study. All patients in Part A will receive treatment 
with orally administered ulixertinib. Patients in Part B will receive either treatment with 
orally administered ulixertinib or the physician’s choice of treatment in a 2:1 ratio. In 
Part B, if a patient progresses on the physician’s choice of treatment then they may 
crossover to the ulixertinib arm. 
Part B randomization will be performed as total enrollment rather than on a site basis. 
Randomization/enrollment in both parts will be performed by using Interactive 
Voice/Web Response System (IxRS). Once written consent has been given by the 
patient, all inclusion/exclusion criteria must be checked by the investigator in order to 
confirm eligibility prior to IxRS randomization/enrollment procedures. In Part B, the 
IxRS will randomly assign the patient to one of the two treatment arms (ulixertinib or 


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the physician’s choice of treatment). In both parts, the IxRS will assign the patient a 
unique patient identification number. This patient identification number will then be 
reported on all eCRF pages and in any study documents. 
8.4 
STUDY DRUG COMPLIANCE 
The investigator will dispense the study drug only for use by patients enrolled in the 
study as described in this protocol. The study drug is not to be used for reasons other 
than those described in this protocol. 
The investigator or other study staff will supervise study drug treatment given in the 
clinic and instruct the patient on study drug self-administration. Patients will be asked 
to bring their study drug container with them at each visit and compliance with 
protocol-defined study drug intake will be checked by pill count. In case of non-
compliance, the patients will be instructed again. 
8.5 
CONCOMITANT THERAPY AND RESCUE MEDICATION 
A detailed history of medications, including prior anti-cancer therapies, and 
procedures will be documented for each patient. Concomitant medications (especially 
changes in medication, including any anti-cancer therapies) will be documented for 
each patient at each scheduled visit.   
Necessary supportive care such as anti-emetics and anti-diarrheals, etc., will be 
allowed. Medications that are known to be strong inhibitors or inducers of CYP3A4, 
CYP2D6, and CYP1A2 are not permitted during the study (for list of non-permitted 
drugs, see Appendix 1). 
If deemed necessary by the treating investigator and reviewed by the medical 
monitor, palliative radiation therapy for a single site of bone or brain metastasis is 
allowed provided that it is the only site of disease progression. The radiation field 
must not affect any of the target lesions designated for disease assessment. Protocol 
treatment will be held during radiation therapy and will be re-started after any acute 
toxicities have resolved. 
All medications administered from 30 days prior to the commencement of study 
treatment (Day 1) through the end of the treatment period will be recorded on the 
eCRF. Any changes of dosages of medication will also be noted. 


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9 
STUDY DRUG DISCONTINUATION AND PATIENT 
DISCONTINUATION/WITHDRAWAL 
9.1 
DISCONTINUATION OF STUDY DRUG 
Discontinuation from the study drug does not mean discontinuation from the study, 
and remaining study procedures should be completed as indicated by the study 
protocol. If a clinically significant finding is identified (including, but not limited to 
changes from baseline) after enrollment, the investigator or qualified designee will 
determine if any change in patient management is needed. Any new clinically relevant 
finding will be reported as an AE. 
9.2 
PATIENT DISCONTINUATION CRITERIA 
Treatment is to be discontinued for any of the following reasons: 
• Disease progression (at the discretion of the investigator). If brain or bone 
metastases develop while on study, patients may be permitted to continue on 
study, after discussion with the medical monitor, if the overall risk/benefit is 
still favorable. 
• Unacceptable toxicity. 
• Changes in the patient's condition which render the patient unacceptable for 
further treatment (at the discretion of the investigator). 
• Investigator’s judgement. 
Patients who have been discontinued from treatment should still be followed for 
survival. 
9.3 
PATIENT WITHDRAWAL FROM THE STUDY 
Patients must be withdrawn from the study for any of the following reasons: 
• Withdrawal of informed consent. 
• Patient non-compliance (at the discretion of the investigator). 
• Patient becomes pregnant (withdrawal is required). 
• Patient is lost to follow-up. 
Patients will also to be withdrawn at any time if the investigator concludes that it would 
be in the patient’s best interest for any reason. Protocol violations will not lead to 
patient withdrawal unless they constitute a significant risk to the patient’s safety. 
Patients can voluntarily withdraw from the trial for any reason at any time. They are to 
be considered withdrawn if they state an intention to withdraw, fail to return for visits, 
became lost to follow up for any reason, or if any of the following occurs: 
• Discovery of patient ineligibility. 


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• Missed / unscheduled / off-schedule / incomplete / incorrect assessments that 
result in patients being put at risk. 
Patients who withdraw at any time preceding the last visit of Cycle 2 (Day 43) will 
constitute an early discontinuation, will not be replaced, and will be evaluated in the 
efficacy analysis. If patients withdraw due to progressive disease or AEs, replacement 
of such patients potentially introduces bias into the study. If a patient withdraws for 
other reasons, replacement of the patient will be decided by the Safety Monitoring 
Committee.  
The investigator must determine the primary reason for a patient’s withdrawal from 
the study and record this information on the eCRF. 
9.4 
LONG TERM FOLLOW UP 
Upon discontinuation of study drug, patients will be followed for survival and the 
initiation of subsequent anticancer therapy for 18 months from the date of study 
therapy initiation. Patients that discontinue study treatment for any reason other than 
disease progression, must continue to have disease assessments every 8 weeks (± 7 
days) until disease progression or the initiation of subsequent anticancer therapy. 
Patients or their legally authorized representatives will be contacted every three 
months (± 7 days) until death, end of the study, or patient withdrawal of consent, 
whichever comes first. Survival and subsequent treatment status may be collected by 
public records, medical records, or by contacting the patient or their legally authorized 
representative by phone. All efforts should be made to contact the patient at these 
time points. Refer to Section 9.5 for Lost to Follow-Up guidelines. 
9.5 
LOST TO FOLLOW-UP 
A patient will be considered lost to follow-up if they fail to return for scheduled visits 
and is unable to be contacted by the study site staff. 
The following actions will be taken if a patient fails to return to the clinic for a required 
study visit: 
• The site will attempt to contact the patient and reschedule the missed visit 
and counsel the patient on the importance of maintaining the assigned visit 
schedule and ascertain if the patient wishes to and/or should continue in the 
study. 
• Before a patient is deemed lost to follow-up, the investigator or designee will 
make every effort to regain contact with the patient (where possible, 3 
telephone calls and, if necessary, a certified letter to the patient’s last known 
mailing address). These contact attempts should be documented in the 
patient’s medical record or study file. 


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• Should the patient continue to be unreachable, they will be considered to 
have withdrawn from the study with a primary reason of lost to follow-up. 


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10 STUDY ASSESSMENTS AND PROCEDURES 
10.1 METHODS OF ASSESSMENT AND CRITERIA FOR EVALUATION 
Every effort should be made to ensure that the protocol-required tests and procedures 
are completed as described. However, it is anticipated that from time to time there 
may be circumstances outside of the control of the investigator that may make it 
unfeasible to perform the test. In these cases, the investigator will take all steps 
necessary to ensure the safety and well-being of the patient. When a protocol-required 
test cannot be performed, the investigator will document the reason for this and any 
corrective and preventative actions that were taken to ensure that normal processes 
are adhered to as soon as possible. 
All trial data will be recorded on the electronic case report forms (eCRFs). Blood and 
tissue biopsy specimens will be sent to a third-party laboratory vendor for analysis. 
10.1.1 
Demographic Data 
Include date of birth (DOB), age, gender, race, and ethnicity. 
10.1.2 
Medical and Cancer History 
A complete medical history will be obtained from each patient including the specifics 
of their advanced malignancy and molecular alterations. For female patients of child-
bearing potential, the date of the last menstrual period will be noted. Smoking history 
and prior cancer therapy will be recorded. Data will be reviewed and updated at each 
visit. 
10.1.3 
Prior and Concomitant Medications 
See Section 8.5. 
10.1.4 
Vital Signs and Physical Examination 
Height should be recorded at screening only. Body weight should be recorded at each 
visit. 
Vital sign records should include body temperature, systolic/diastolic blood pressure 
(BP), and pulse rate. BP should be assessed on the same arm during the study. 
Full physical examination evaluations at screening should include general 
appearance, skin, neck, eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph 
nodes, extremities, and neurological examinations. Subsequent targeted physical 
exams should include body systems as appropriate. 
Performance status (ECOG) should be assessed within 72 hours before start of study 
treatment and at each study visit (see Appendix 3). 


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10.1.5 
Ophthalmology Examination 
A full ophthalmic examination will be performed at the time points described in the 
SoA or when clinically indicated. They will include best-corrected visual acuity (BCVA), 
visual field examination (VF), intraocular pressure, external eye examination, and 
dilated fundoscopy. For additional details refer to study manual.  
Any patient experiencing vision changes must stop taking ulixertinib and have an 
ophthalmic evaluation. Ulixertinib may be re-started when symptoms resolve. 
10.1.6 
Laboratory Assessments 
The following clinical laboratory tests will be performed: 
• Hematology (blood sample: EDTA) – hemoglobin, hematocrit, white blood 
cells (WBC) count with differential, red blood cells (RBC) count, and platelet 
count. 
• Blood Chemistry (blood sample: serum) – albumin, alkaline phosphatase 
(ALP), total bilirubin, calcium, chloride, creatinine, glucose, inorganic 
phosphorus, potassium, total protein, alanine aminotransferase (ALT), 
aspartate aminotransferase (AST), sodium, blood urea nitrogen (BUN), uric 
acid, lactic dehydrogenase (LDH), cholesterol, and triglycerides.  
• If the total bilirubin concentration is increased above 1.5 times the upper 
normal limit, total bilirubin should be differentiated into the direct and indirect 
reacting bilirubin. 
• Urinalysis – specific gravity, pH; semi-quantitative "dipstick" evaluation of 
glucose, protein, bilirubin, ketones, leukocytes, and blood and a microscopic 
examination including RBC, WBC, and casts will be performed if the dipstick 
is abnormal. 
• Pregnancy – Beta-hCG Qualitative Urine or Serum 
After Cycle 2, clinical chemistry (to include calcium and inorganic phosphorus), 
hematology, and urinalysis may be performed once per cycle or more frequently at 
the investigator’s discretion. 
Blood chemistry will be analyzed at each trial center by a certified laboratory and a 
report of the laboratory values will be sent to the investigator. The investigator or 
designee will review the laboratory report after receipt of the results and assess the 
clinical significance of all abnormal values. Results must be reviewed prior to dosing 
and appropriate action taken for any clinically significant abnormal values. Values will 
be documented on the laboratory report until stabilized, or the laboratory value returns 
to a clinically acceptable range (regardless of relationship to study medication) or 
baseline.  


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Any laboratory value that remains abnormal at the end-of-study (EOS) and that is 
considered clinically significant will be followed according to accepted medical 
standards for up to 30 days or until resolution of the abnormality or return to baseline. 
10.1.7 
Electrocardiogram (ECG) 
All patients require a single 12-lead ECG measurement. The parameters to be 
recorded are QT, QTc, QTC F, PR, and QRS. A standard 12-lead (with a 10-second 
rhythm strip) tracing will be used for all ECGs. Patients should be supine for 5 minutes 
prior to the ECG. 
Patients with a normal ECG in screening do not need to have repeat ECGs in 
subsequent cycles unless clinically indicated. 
10.1.8 
Echocardiogram (ECHO) or Multi-Gated Acquisition (MUGA) 
LVEF will be assessed by ECHO or MUGA performed at screening and as clinically 
indicated. 
10.1.9 
Disease Status 
The decision for body areas to be scanned will depend on the extent of disease. 
Disease assessments must include all known or suspected disease sites. Imaging will 
be performed on the abdomen, chest, pelvis, and the site of the primary tumor if 
elsewhere.   
Tumor measurements based on physical examination will occur at baseline and on 
the first day of each treatment cycle. Tumor assessments will be made by 
CT/MRI/Physical Exam prior to dose initiation, at the 1st protocol-specified tumor 
measurement evaluation at the beginning of Cycle 2 and then every 2 cycles, and at 
End of Treatment. Patients that discontinue study treatment for any reason other than 
disease progression, must continue to have disease assessments every 8 weeks (± 7 
days) until disease progression or the initiation of subsequent anticancer therapy. The 
schedule of tumor assessments should be fixed according to the calendar, starting 
with cycle one day one, regardless of treatment delays or interruptions due to toxicity. 
The same imaging technique used to characterize each identified and reported lesion 
at baseline will be employed in the following tumor assessments. 
10.1.10 Tissue Biopsy 
Tumor biopsy during the screening period and during Visit 5 (Day 28) of treatment in 
Part A is required. If a patient has undergone a biopsy within ≤ 6 months and has not 
received any anticancer treatment since undergoing the biopsy, archival tissue from 
this biopsy may be used to fulfill screening tissue requirements. Assays to investigate 
pharmacodynamic markers of ERK inhibition in addition to exploratory analysis to 


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evaluate adaptive response in pathways in addition to MAPK will be deployed. These 
may include, but are not limited to, RPPA, Nanostring, and RNA-exome. An optional 
tumor biopsy is requested at end of treatment; this is not a mandatory collection but 
strongly encouraged in patients relapsing following robust response to ulixertinib. 
Broad molecular profiling will be applied to end of treatment/at relapse tumor samples 
to aid scientific understanding of mechanisms of resistance to ERK inhibition.   
10.1.11 Blood Samples for Pharmacokinetic (PK) Analysis 
In Part A only, plasma samples will be collected for PK analysis at Visit 4, pre-dose. 
Patients need to be at steady state for this collection, which means 10 consecutive 
doses, or 5 consecutive days. 
10.1.12 Blood Samples for Pharmacodynamic (PD) and ctDNA Analysis 
In Part A only, blood samples will be collected for PD and ctDNA analysis at Baseline 
and Visit 4. Samples for ctDNA will also be collected at Visit 5 and End of Treatment. 
Blood samples for pharmacodynamic analyses will be taken from all patients in Part 
A until the sponsor determines sampling may be discontinued based on accumulated 
patient experience. 
10.1.13 Adverse Events 
Toxicity/severity of AEs will be assessed using the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTCAE) Grading System, Version 5.0, 
as detailed on web page: http://ctep.cancer.gov. 
Also see Section 10.6. 
10.2 CRITERIA FOR EVALUATION 
10.2.1 
Efficacy 
Overall response rate (ORR), duration of response (DOR), and progression free 
survival (PFS) are primary or secondary objectives and will be evaluated by standard 
RECIST v1.1 criterion per local investigator’s assessment and, for Part B only, 
independent, third-party review. 
The response criteria for target lesions are defined as follows: 
• 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. 
• Partial Response (PR): At least a 30% decrease in the sum of diameters of 
target lesions, taking as reference the baseline sum diameters. 


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• Progressive Disease: 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 1 or more new lesions is also 
considered progression). 
• Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor 
sufficient increase to qualify for Progressive Disease, taking as reference the 
smallest sum diameters while on study. 
10.2.2 
Pharmacokinetics (PK) 
• Blood samples will be collected to measure ulixertinib (BVD-523) and 
selected metabolite pharmacokinetic parameters.   
• If a patient changes doses, an additional blood sample will be collected at 
steady state (for each dose level a patient experiences). 
10.2.3 
Circulating Tumor DNA 
• Blood samples will be collected to measure circulating tumor DNA, including, 
but not limited to, BRAF and MEK alterations. 
10.2.4 
Pharmacodynamics (PD) 
• Evaluation of tissue biopsies, and/or blood to assess biomarkers such as 
dual-specificity phosphatase (DUSP), RSK, and c-Myc. 
• Additional biomarkers may be identified and measured as appropriate.  
10.3 DESCRIPTION OF STUDY VISITS FOR PATIENTS RECEIVING 
ULIXERTINIB 
10.3.1 
Description of Study Visits for Cycle 1 
Procedures performed in the first cycle are specified in the Schedule of Activities 
(SoA). Patients receiving multiple cycles of treatment will not have blood drawn for PK 
and PD measurements after Cycle 1 unless additional PK and PD data are deemed 
necessary after initial analysis or the patient changes dose. 
10.3.1.1 
Visit 1 (Day -28 to -1); Screening 
The following procedures will be performed at Visit 1 (Screening): 
• Obtain written informed consent (before start of any study-related procedures 
that are not considered Standard of Care) including optional consents (Note: 
informed consent may be obtained up to -28 days to allow flexibility in 
scheduling of the screening procedures). 


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• Evaluate all inclusion and exclusion criteria to ensure that patients meet all 
inclusion criteria and none of the exclusion criteria. 
• Record demographic data including date of birth (DOB), age, gender, race, 
and ethnicity.  Where full DOB is collected, initials will not be used. 
• Review medical history including all previous cancer treatments, best 
response to those cancer treatments, and reason for stopping them. 
• Record prior and concomitant medications including start/stop dates, 
indication, dose, toxicities, and frequency taken within 30 days of Cycle 1, 
Day 1. 
• Measure and record height and weight. 
• Record vital signs. Measure body temperature, systolic / diastolic BP, and 
pulse rate. 
• Perform and record physical examination. 
• Assess and record performance status (ECOG) within 72 hours before start 
of treatment. 
• Perform and record ophthalmology examination (ulixertinib patients only). 
• Collect blood for a serum pregnancy test for female patients who are not 
postmenopausal or surgically sterile. If positive, repeat and confirm results 
prior to Visit 2. A second positive test will result in exclusion of the patient 
from the study. 
• Collect blood samples for blood chemistries, hematology, and calculated 
creatinine clearance (using Cockcroft-Gault) within 72 hours before start of 
treatment. Analyze, review, and report any clinically significant abnormalities 
to the medical monitor before dosing. 
• Collect urine samples for urinalysis within 72 hours before start of treatment. 
• Obtain a 12-lead electrocardiogram (ECG), and echocardiogram (ECHO) or 
multi-gated acquisition (MUGA) for left ventricular ejection fraction (LVEF). 
• Assess and record current disease status within 28 days. Tumor 
assessments will be made by CT/MRI/Physical Exam. 
• PART A only: Tissue biopsy within -28 days of Visit 1 (required unless 
investigator and medical monitor deems collection inadvisable). If a patient 
has undergone a biopsy within ≤ 6 months and has not received any 
anticancer treatment since undergoing the biopsy, archival tissue from this 
biopsy may be used to fulfill screening tissue requirements. 
• Complete Screening/Enrollment Form and submit to medical monitor for 
review prior to treatment of patient. 
• For Part B only, prior to Visit 2, obtain a randomization code as outlined in 
Section 8.3. 


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10.3.1.2 
Visit 2 (Day 1 ± 0); Baseline/Drug Dispensing/Initiation of 
Treatment 
The following procedures will be performed at Visit 2 (Baseline): 
• Review Screening/Enrollment Form to confirm consent to enroll was obtained 
from medical monitor or sponsor. 
• Review all inclusion and exclusion criteria to ensure that patients meet all 
inclusion criteria and none of the exclusion criteria. 
• Review medical history for any changes since Screening Visit.  
• Record medications including start/stop dates, indication, dose, toxicities, and 
frequency for any changes since Screening Visit. 
• Measure and record weight. 
• Record vital signs. Measure body temperature, systolic / diastolic BP, and 
pulse rate. 
• Assess and record performance status (ECOG), if not done during Screening 
Visit, within 72 hours of start of treatment. 
• ONLY if the screening pregnancy test was performed more than 1 day 
previously, collect blood for a repeat serum pregnancy test for female patients 
who are not postmenopausal or surgically sterile. 
• Collect pre-dose blood samples for blood chemistries, hematology and 
creatinine clearance if not done during Screening Visit within 72 hours of start 
of treatment. 
• Collect pre-dose urine samples for urinalysis. 
• PART A only: Collect pre-dose blood samples for pharmacodynamic (PD) and 
ctDNA analyses. 
• Administer first dose of ulixertinib. 
• PART A only: Collect 4-hour (± 10 minutes) post-dose blood samples for 
pharmacodynamic analyses.  
• Assess and record AEs. 
• Dispense study drug and instruct patients how to take study drug, daily every 
12 hours ± 2 hours with at least 8 ounces of water and food.  
• Inform patients of the potential photosensitizing effects of ulixertinib and 
instruct them to avoid sunlight and wear protective clothes, sunglasses, and 
apply sunblock when outside, including when driving a car. 
10.3.1.3 
Visit 3 (Day 8 ± 3) 
The following procedures will be performed at Visit 3: 
• Review medical history. 
• Record concomitant medications including start/stop dates, indication, dose, 
toxicities, and frequency taken after Visit 2. 


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• Measure and record weight. 
• Record vital signs. Measure body temperature, systolic / diastolic BP, and 
pulse rate. 
• Assess and record performance status (ECOG). 
• Collect blood samples for blood chemistries, hematology, and creatinine 
clearance. 
• Collect urine samples for urinalysis. 
• Assess and record AEs. 
• Obtain all unused study drug from patient. 
• Assess study drug compliance by pill count. 
• Dispense drug supply for self-dosing and remind patients of dosing 
instructions. 
10.3.1.4 
Visit 4 (Day 15 ± 3) 
The following procedures will be performed at Visit 4: 
• Review medical history. 
• Record concomitant medications including start/stop dates, indication, dose, 
toxicities, and frequency taken after Visit 3. 
• Measure and record weight. 
• Record vital signs. Measure body temperature, systolic / diastolic BP, and 
pulse rate. 
• Assess and record performance status (ECOG). 
• Collect blood samples for blood chemistries, hematology, and creatinine 
clearance. 
• PART A only: Collect pre-dose trough blood samples for pharmacokinetic 
(PK), pharmacodynamic (PD), and ctDNA analyses. These assessments 
should be collected when the patient reaches steady state. Steady state 
refers to patients who have received at least 5 days, or 10 consecutive doses, 
of investigational product. If patients are not at steady state, these 
assessments will be rescheduled and completed at the next visit in which 
steady state is achieved. 
• Administer first daily dose of ulixertinib. 
• PART A only: Collect 4-hour (± 10 minutes) post-dose blood samples for 
pharmacodynamic analyses. 
• Collect urine samples for urinalysis. 
• Assess and record AEs. 
• Obtain all unused study drug from patient. 
• Assess study drug compliance by pill count. 
• Dispense study drug supply for self-dosing. 


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10.3.2 
Description of Study Visits for Cycle 2 
10.3.2.1 
Visit 5 (Day 29 ± 3, first day of Cycle 2) 
The following procedures will be performed at Visit 5: 
• Review medical history. 
• Record concomitant medications including start/stop dates, indication, dose, 
toxicities, and frequency taken after Visit 4. 
• Measure and record weight. 
• Record vital signs.  Measure body temperature, systolic / diastolic BP, and 
pulse rate. 
• Assess and record performance status (ECOG). 
• PART A only: Tissue biopsy (required unless investigator and medical 
monitor deems collection inadvisable).   
• PART A only: Collect blood samples for ctDNA. 
• Collect blood samples for blood chemistries, hematology, and creatinine 
clearance. 
• Collect urine samples for urinalysis. 
• Perform urine pregnancy test for female patients who are not 
postmenopausal or surgically sterile.  If urine test is positive, collect blood for 
a serum pregnancy test.  If serum pregnancy test is positive, withdraw patient 
from study and contact the medical monitor. 
• Assess and record AEs. 
• Obtain all unused study drug from patient. 
• Assess study drug compliance by reviewing pill count. 
• Assess and record disease status (every 2 cycles).  
• Dispense study drug supply for self-dosing. Extra doses may be dispensed 
at the investigator’s discretion to ensure continuous dosing. 
10.3.2.2 
Visit 6 and 7 
Cycle 2 visits 6 and 7 procedures are similar to Cycle 1 visit 3, although no 
pharmacokinetic or pharmacodynamic measurements will be made unless 
specifically requested by investigator or the patient changes dose level. 
10.3.3 
Cycle 3 and Subsequent Cycles Visit (Day 1 ± 3 of each cycle) 
Cycle 3 and subsequent cycles have one scheduled visit per cycle. No 
pharmacokinetic or pharmacodynamic measurements will be made unless specifically 
requested by the investigator or the patient changes dose level. 
The following procedures will be performed at the Cycle 3 and Subsequent Cycles 
Visit: 


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• Review medical history. 
• Record concomitant medications including start/stop dates, indication, dose, 
toxicities, and frequency taken since previous visit. 
• Measure weight. 
• Record vital signs. Measure body temperature, systolic / diastolic BP, and 
pulse rate. 
• Assess and record performance status (ECOG). 
• Collect blood samples for blood chemistries, hematology, and creatinine 
clearance. 
• Collect urine samples for urinalysis. 
• Perform urine pregnancy test for female patients who are not 
postmenopausal or surgically sterile. If urine test positive, test, collect blood 
for a serum pregnancy test. 
• Assess and record disease status (every 2 cycles). 
• Assess and record AEs. 
• Obtain all unused study drug from patient. 
• Assess study drug compliance by reviewing pill count. 
• Dispense study drug supply for self-dosing. Extra doses may be dispensed 
at the investigator’s discretion to ensure continuous dosing. 
10.3.4 
Description of Study Visits for Patients Enrolled in Part B and 
Receiving Physician’s Choice of Treatment 
Study procedures for patients enrolled in Part B and randomized to physician’s choice 
of treatment will be the similar to those for patients receiving ulixertinib; however, no 
pharmacokinetic or pharmacodynamic samples will be collected in Part B, and an 
ophthalmology examination will be performed only for patients receiving ulixertinib. 
Appropriate SoC monitoring can be completed at the discretion of the investigator. If 
clinical experience gained in Part A requires significant deviations in Part B from the 
procedures in Part A, these changes will be addressed in a protocol amendment.  
10.3.5 
End of Treatment Visit 
At the time of study drug discontinuation, the End of Treatment (EOT) Visit should be 
completed for all patients within 14 ± 3 days after the last dose of study drug, and 
every effort should be made to perform the procedures required. The following 
procedures will be performed at EOT Visit: 
• Review medical history. 
• Record concomitant medications including start/stop dates, indication, dose, 
toxicities, and frequency taken since previous visit. 
• Measure and record weight. 


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• Record vital signs. Measure body temperature, systolic / diastolic BP, and 
pulse rate. 
• Assess and performance status (ECOG). 
• PART A only: Collect blood samples for ctDNA. 
• PART A only: Tissue biopsy, optional, but strongly encouraged. 
• Collect blood samples for blood chemistries, hematology and creatinine 
clearance. 
• Collect urine samples for urinalysis. 
• Perform urine pregnancy test for female patients who are not 
postmenopausal or surgically sterile. If urine test is positive, collect blood for 
a serum pregnancy test. 
• Assess and record disease status. 
• Assess and record AEs. 
• Obtain all unused study drug from patient. 
• Assess study drug compliance by reviewing pill count. 
• Complete end of treatment form. 
10.3.6 
Safety Follow-Up Assessment 
Patients will return to the clinic or will be contacted for a safety follow-up assessment 
30 days ± 3 days after the last dose of study drug was taken; or earlier if subsequent 
therapy for advanced malignancy is initiated prior to 30 days ± 3 days. Only 
information about AEs and SAEs will be collected at this visit. 
10.3.7 
Follow Up 
Patients will be followed for survival and the initiation of subsequent anticancer 
therapy for 18 months from the date of study therapy initiation, as outlined in 
Section 9.4. 
Patients that discontinue study treatment for any reason other than disease 
progression, must continue to have disease assessments every 8 weeks (± 7 days) 
until disease progression or the initiation of subsequent anticancer therapy. 
10.3.8 
Unscheduled Visits 
Additional visits can be performed as appropriate and at the discretion of the 
investigator. All unscheduled study visits, procedures, examinations, clinical 
laboratory evaluations etc., will be noted in the patient’s medical record and the eCRF 
including: 
• Reason for visit/procedure. 
• Follow-up. 


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• Recording of AEs and use of concomitant measures. 
10.4 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
10.4.1 
Definition of Adverse Events (AE) 
An AE is defined as any untoward medical occurrence in a patient administered a 
medicinal product that does not necessarily have a causal relationship with this 
treatment. An AE can, therefore, be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal (investigational) product, whether or not related to the study 
(investigational) product. This includes an exacerbation of pre-existing conditions or 
events, intercurrent illnesses, drug interaction, or the significant worsening of the 
indication under investigation that is not recorded elsewhere in the eCRF under 
specific efficacy assessments. Anticipated fluctuations of pre-existing conditions, 
including the disease under study that does not represent a clinically significant 
exacerbation or worsening, need not be considered AEs. 
It is the responsibility of the investigator to document all AEs that occur during the 
study. AE information will be elicited by asking the patient a non-leading question, for 
example, “Have you experienced any new or changed symptoms since we last 
asked/since your last visit?”. AEs should be reported on the appropriate page of the 
eCRF. 
10.4.2 
Definition of Serious Adverse Events (SAE) 
A Serious Adverse Event (SAE) is any untoward medical occurrence that occurs at 
any dose (including after the ICF is signed and prior to dosing) that: 
• Results in death 
• Is life-threatening (patient is at immediate risk of death from the event as it 
occurred) 
• Requires in-patient hospitalization (formal admission to a hospital for medical 
reasons) or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Results in a congenital anomaly/birth defect 
Important medical events that may not result in death, are not life-threatening, or do 
not require hospitalization may be considered SAEs when, based on appropriate 
medical judgment, they may jeopardize the patient and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. Examples 
of such events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in in-
patient hospitalization, or the development of drug dependency or drug abuse. 


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Hospitalizations for elective surgery or other medical procedures that are not related 
to a treatment-emergent AE are not considered SAEs. 
Progression of the malignancy under study (including signs and symptoms of 
progression) should not be reported as an SAE unless the outcome is fatal during the 
study or within the safety reporting period (see below). If the malignancy has a fatal 
outcome during the study or within the safety reporting period, then the event should 
be reported using the term “disease progression” with a CTCAE severity of Grade 5. 
10.4.3 
Classification of an Adverse Event 
10.4.3.1 
Severity of an Event 
The severity of the AE will be graded according to the NCI CTCAE Grading Scale 
Version 5.0 (see the NCI CTCAE web page at http://ctep.cancer.gov for details). For 
AEs not covered by NCI CTCAE, the severity will be characterized according to the 
following definitions: 
• Mild events are usually transient and do not interfere with the patient’s daily 
activities. 
• Moderate events introduce a low level of inconvenience or concern to the 
patient and may interfere with daily activities. 
• Severe events interrupt the patient’s usual daily activities. 
• Life-threatening events require urgent intervention. 
• Fatal events result in the patient’s death. 
10.4.3.2 
Relationship to Study Drug 
The investigator will make a judgment regarding whether or not the AE was related to 
study drug, as outlined below, and in accordance with FDA guidance of 2012. 
Unrelated 
The AE is unlikely to have been caused by study drug. 
Possibly related 
It is unclear whether the AE may have been caused by study 
drug, but there is at least a reasonable possibility of a 
relationship, or a relationship cannot be ruled out. 
Related 
The AE is likely to have been caused by study drug. 
10.4.3.3 
Expectedness 
The CRO DSPV group and CRO medical monitor will be responsible for determining 
whether an AE is expected or unexpected. An AE will be considered unexpected if the 
nature, severity, or frequency of the event is not consistent with the risk information 
previously described for the study drug, as documented within the most recent version 
of the Investigator’s Brochure. 


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10.4.4 
Time Period and Frequency for Event Assessment and Follow-up 
The occurrence of an AE or SAE may come to the attention of study personnel during 
study visits and interviews of a study patient presenting for medical care, or upon 
review by a study monitor. At each study visit, the investigator or their designee will 
inquire about the occurrence of AE/SAEs since the last visit. 
Any medical condition that is present at the time that the patient is screened will be 
considered as baseline and not reported as an AE. However, if the study patient’s 
condition deteriorates at any time during the study, it will be recorded as an AE. 
Changes in the severity of an AE will be documented to allow an assessment of the 
duration of the event at each level of severity to be performed. AEs characterized as 
intermittent require documentation of onset and duration of each episode. 
All reportable events will be recorded with start dates occurring any time after informed 
consent is obtained through and including 30 calendar days after the last 
administration of ulixertinib. Any SAE occurring after the reporting period must be 
promptly reported if a causal relationship to the study product is suspected. If the 
patient begins a new anti-cancer therapy, the safety reporting period ends at the time 
the new treatment is started, however, death must always be reported when it occurs 
during the 30-day reporting period irrespective of intervening treatment.  
All events will be followed for outcome information in accordance with good medical 
practice until they are resolved, stabilize, or judged no longer clinically significant or, 
if a chronic condition, until fully characterized. Any AEs that are considered drug-
related (possibly related, related) must be followed until resolution or until stabilization. 
10.4.4.1 
Post-Study Adverse Events and Serious Adverse Events 
All unresolved AEs will be followed by the investigator until the events are resolved 
(see Section 10.4.4), the patient is lost to follow-up, or the AE is otherwise explained.  
At the last scheduled visit, the investigator should instruct each patient to report any 
subsequent event(s) that the patient, or the patient’s personal physician, believes 
might reasonably be related to participation in this study. Prior to the conclusion of the 
study at the site, the investigator should notify the designated CRO safety team (see 
Section 10.4.6) of any death or AE occurring at any time after a patient has 
discontinued or terminated study participation that may reasonably be related to this 
study. After study conclusion the investigator should notify BioMed Valley Discoveries, 
Inc., or their CRO designee, of any death or AE they are aware of occurring at any 
time after a patient has discontinued or terminated study participation that may 
reasonably be related to this study. BioMed Valley Discoveries, Inc., should also be 
notified if the investigator should become aware of the development of cancer or of a 


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congenital anomaly in a subsequently conceived offspring of a person that has 
participated in this study. 
10.4.5 
Adverse Event Reporting 
All AEs, including local and systemic reactions, not meeting the criteria for SAEs will 
be captured on the appropriate eCRF. Information to be collected includes event 
description, time of onset, investigator’s assessment of severity, seriousness, 
relationship to the study product (assessed only by those with the training and 
authority to make a diagnosis), and time of resolution/stabilization of the event. In 
order to avoid vague, ambiguous, or colloquial expressions, the AE should be 
recorded in standard medical terminology rather than the patient’s own words.  
Whenever possible, the investigator should combine signs and symptoms that 
constitute a single diagnosis. The action taken and the outcome must also be 
recorded. All AEs occurring while on study must be documented appropriately 
regardless of relationship. All AEs will be followed to adequate resolution. 
10.4.6 
Serious Adverse Event Reporting 
All SAEs must be entered into the eCRF within 24 hours of first knowledge of the event 
by study personnel. It is important that the investigator provide their assessment of 
relationship to study drug at the time of the initial report. Follow-up information must 
also be reported within 24 hours of first knowledge. Entry of an SAE (or updated SAE 
information) into the eCRF will trigger an automatic alert to the designated CRO safety 
team. Timely notification of an event supersedes the requirement to have all 
information at the time of the initial report.   
If the EDC system is not available, the investigator must send a completed paper 
SAE Report Form to the CRO safety team via email or fax as follows, within 24 hours.  
If no acknowledgement is received within one working day, the report should be re-
submitted. 
Safety Report Email Address: sae@cmedresearch.com  
Safety Report Fax No.: 866.240.8830 (US) or +44 1403 330459 (international) 
The SAE data must be entered into the eCRF as soon as it becomes available. 
The following information must be reported on the eCRF SAE report form: 
• Protocol number 
• Site and/or Investigator number 
• Patient number 
• Demographic data 
• Brief description of the event 


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• Onset date and time 
• Resolution date and time, if the event resolved 
• Current status, if event not yet resolved 
• Any concomitant treatment and medication 
• Investigator’s assessment of whether the SAE was related to investigative 
product or not 
• Outcome of the event if available 
The CRO safety team will contact the site for clarification of data entered onto the 
eCRF, or to obtain missing information. In the event of questions regarding SAE 
reporting, the site may contact Cmed Drug Safety and Pharmacovigilance via email 
sae@cmedresearch.com.  
Unexpected serious suspected adverse reactions are subject to expedited reporting 
to FDA.  The CRO safety team is responsible for submitting reports of AEs associated 
with the use of the drug that are both serious and unexpected to the FDA and to 
investigators participating in ongoing clinical studies with the study medication, 
according to 21 CFR 312.32 and the applicable guidance documents.  All investigators 
participating in ongoing clinical studies with the study medication are responsible for 
prompt submission of these reports to their Institutional Review Board (IRB) or Ethics 
Committee (EC). 
10.4.7 
Overdose 
No information on treatment of overdose of ulixertinib is currently available. In the 
event of an overdose, within 24 hours of awareness, the overdose should be reported 
as an AE and the medical monitor should be notified. All overdose cases will be 
discussed by the sponsor and medical monitor on a case-by-case basis. 
10.4.8 
Reporting of Pregnancy 
Each pregnancy in a patient or partner of a patient on ulixertinib must be reported to 
the designated CRO safety team within 24 hours of learning of its occurrence, on a 
Pregnancy Notification Form and via the contact details noted in Section 10.4.6.  If a 
patient becomes pregnant, study drug administration must be discontinued 
immediately. The pregnancy should be followed up to determine outcome, including 
spontaneous or voluntary termination, details of the birth, and the presence or 
absence of any birth defects, congenital abnormalities, or maternal and/or newborn 
complications. Follow-up and documentation must occur even if the patient withdraws 
from the study or the study is completed. 
Pregnancy per se is not considered an AE unless there is cause to believe that the 
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Hospitalization for normal delivery of a healthy newborn should not be considered a 
SAE. Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, 
stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs and must be 
reported as such. 
The avoidance of pregnancy or fathering a child is suggested for 3 months following 
the discontinuation of ulixertinib therapy. No information is currently available 
regarding the effects of ulixertinib on fertility, gestation or subsequent child 
development. 
Any pregnancy within 3 months after the last study drug administration should be 
reported to the study investigator and to the CRO. 


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11 STATISTICAL CONSIDERATIONS 
11.1 STATISTICAL ANALYSIS PLAN 
A formal detailed statistical analysis plan (SAP), covering statistical analyses planned 
for Part A and Part B, will be developed and finalized prior to the main analysis of 
Part A data. This section is a summary of the planned statistical analyses at the time 
of protocol development. 
A separate analysis plan will be developed specifically for the safety reviews to be 
conducted by the SMC. 
11.2 SAMPLE SIZE DETERMINATION 
11.2.1 
Part A 
Approximately 38 patients will be recruited into each group in Part A. 
With 34 patients in a group and assuming the true ORR is 40%, there is approximately 
80% power to reject the null hypothesis that the true ORR is ≤ 20% in that group, with 
a 1-sided alpha of 5%. Assuming a 10% drop out rate, up to 38 patients will be 
recruited in each group. 
11.2.2 
Part B 
It is not possible to accurately calculate the required sample size until the histologies 
of interest have been confirmed. Once the histologies of interest have been confirmed 
these calculations will be repeated and the final sample size confirmed. 
Approximately 80-100 patients will be randomized, using a 2:1 ratio, for each histology 
group in Part B.  
Using a 2-sided, log-rank test with a 5% alpha, and assuming a median PFS of 1.7 to 
8.5 months (depending on histology) in the physician’s choice arm and twice as long 
on the ulixertinib arm, approximately 80 to 100 patients will be required in each group 
to achieve 80% power to show a statistically significant difference between the arms.  
This also assumes that each group will take approximately 24 months to accrue and 
the analysis is expected to be performed 18 months following the last patient accrued. 
The anticipated loss to follow-up is estimated to be 10%. 
11.3 RANDOMIZATION 
Part A of this study is open-label, and all patients enrolled in Part A will be treated with 
ulixertinib. 
Part B of this study is open-label, patients will be randomly assigned to receive either 
ulixertinib or the physician’s choice of treatment in a 2:1 ratio. Also see Section 8.3. 


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11.4 ANALYSIS SETS 
11.4.1 
Full Analysis Set 
The full analysis set (FAS) will consist of all patients who received at least one dose 
of study medication. This analysis set will be used for all efficacy analyses. 
For Part B, analyses performed on the FAS will allocate patients’ treatment group as 
randomized. 
11.4.2 
Safety Analysis Set 
The safety analysis set will consist of all patients who received at least one dose of 
study medication. This analysis set will be used for all safety analyses. 
For Part B, analyses performed on the safety population will allocate patients’ 
treatment group as actually received. 
11.4.3 
Per Protocol Analysis Set 
The per-protocol (PP) analysis set will consist of all patients of the FAS who completed 
the study without any major protocol deviations. 
11.5 DATA PRESENTATION 
Descriptive statistics for continuous variables will include the number of patients, 
mean, standard deviation, median, minimum, maximum; frequencies and percentages 
will be displayed for categorical data. 
Summary data will be provided separately for Part A and Part B, and by group/tumor 
histology. 
Data will be analyzed using the SAS system software version 9.4 (or later). 
11.5.1 
Demographic 
Demographic characteristics of patients will be summarized in appropriate tables and 
with descriptive statistics. 
The following characteristics will be summarized in the FAS, PP, and safety analysis 
sets: 
• Age 
• Gender 
• Race 
• Ethnicity 
• Advanced malignancy information including relapsed or refractory status 
• MEK or Atypical BRAF alteration 


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11.5.2 
Baseline Characteristics 
Baseline characteristics will be summarized in appropriate tables and with descriptive 
statistics. 
The following characteristics will be summarized in the FAS, PP, and safety analysis 
sets: 
• Body weight 
• Height 
• ECOG performance status 
• Previous cancer therapies 
11.5.3 
Medical History and Physical Examination 
Medical history and physical examination assessments will be summarized in 
appropriate tables and with descriptive statistics, in the FAS, PP, and safety analysis 
sets. 
11.5.4 
Concomitant Medications or Treatments 
The number and percentage of patients taking prior and concomitant medications will 
be summarized by therapeutic class and preferred term using descriptive statistics.  
All data will be recorded as follows: 
• Prior medication: ended before first day of study drug. 
• Concomitant medication: ongoing at first day of study drug or started after 
first day of study drug. 
11.5.5 
Efficacy Analysis 
All efficacy analyses will be performed using the FAS. 
11.5.5.1 
Part A 
The primary endpoint for Part A is the overall response rate (ORR) within a group. It 
will be defined as the percentage of patients achieving a BOR of confirmed CR and/or 
PR as assessed by the investigator. The ORR will be presented with its 95% 
confidence intervals (CIs). 
All response assessments will be presented using swimmer plots and will be listed by 
patient. 
Sensitivity analyses of the primary analysis will include similar analyses using PP 
analysis set. 
Analyses of secondary efficacy endpoints will include Kaplan-Meier estimates and 
curves, median DoR and respective 95% CIs for analysis of: 


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• Duration of response (DoR): time from first response to disease progression 
or death. Patients with no event will be censored at the last available tumor 
assessment. This analysis will be based on investigator assessment. 
• Progression-free survival over 18 months (PFS): time from first day of trial 
medication to disease progression or death. Patients with no event will be 
censored at the last available tumor assessment. This analysis will be based 
on investigator assessment. 
• Overall survival over 18 months (OS): time from first day of trial medication to 
death. Patients with no event will be censored at the last date the patient is 
known to be alive. 
11.5.5.2 
Part B 
The primary endpoint for Part B is the Progression-Free Survival over 18 months 
(PFS), defined as time from first day of trial medication to disease progression as 
adjudicated by the independent review committee or death. Patients with no event will 
be censored at the last available tumor assessment. PFS will be analyzed using 
Kaplan-Meier estimates and curves, median PFS and respective 95% CIs.  
For each histology, PFS curves will be compared between ulixertinib and physician’s 
choice of treatment using Log Rank Test. The hazard ratio including 95% CI will be 
calculated by Cox’s Proportional Hazards model. 
Sensitivity analyses of the primary analysis will include similar analyses based on 
investigator response assessment and using PP analysis set. 
Analyses of secondary efficacy endpoints will include analyses similar to PFS analysis 
for: 
• Overall survival over 18 months (OS): time from first day of trial medication to 
death. Patients with no event will be censored at the last date the patient is 
known to be alive. 
• Duration of response (DoR): time from first response to disease progression 
or death. Patients with no event will be censored at the last available tumor 
assessment. This analysis will be based on assessment as adjudicated by 
the independent review committee and replicated on investigator 
assessment. 
• Overall response rate (ORR), defined as the percentage of patients achieving 
a BOR of confirmed CR and/or PR, will be presented with its 95% CIs and 
compared between ulixertinib and physician’s choice of treatment using a Chi-
square test. This analysis will be based on assessment as adjudicated by the 
independent review committee and replicated on investigator assessment. 


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11.5.6 
Pharmacokinetic (PK) / Pharmacodynamic (PD) Data 
Pharmacokinetic parameters of ulixertinib (BVD-523) and selected metabolites will be 
measured on Visit 4 (Day 15) in Part A only, this will be a single time-point collection 
prior to taking study drug on this day (trough at steady state).    
Pharmacokinetic values will be presented in by-patient listings, sorted by site, patient 
identifier, and dose. 
In Part A only, the effects of ulixertinib on pharmacodynamic markers will be 
evaluated. Collections will include ctDNA, tissue biopsies and/or blood to assess 
biomarkers. Assays include, but are not limited to, phosphorylation of RSK from whole 
blood, Reverse Phase Protein Arrays (RPPA) to assess protein levels, e.g. DUSP 4/6, 
plus Nanostring and/or RNA-exome to assess mRNA expression in tissue pre- and 
post-ulixertinib treatment. Biomarkers will be explored and listed as appropriate. 
11.5.7 
Safety Analysis 
All safety summaries will be provided for the safety analysis set. 
11.5.7.1 
Adverse Events (AE) 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA).  
System Organ Class, High-Level Group Term, High Level Term, Preferred Term, and 
Lower-Level Term will be attached to the clinical database. 
AEs will be summarized based on the date of onset for the event. Summaries (number 
and percentage of patients) of treatment-emergent AEs will be provided by System 
Organ Class and Preferred Term, by group/tumor histology and overall. 
Treatment-emergent adverse event (TEAE) is defined as any AE that emerges during 
treatment having been absent pre-treatment or worsens relative to the pre-treatment 
state. 
Events that are considered study drug-related, deaths, SAEs, and AEs resulting in 
study drug discontinuation will also be tabulated by System Organ Class and 
Preferred Term. 
A tabulation will also be provided that summarizes treatment-emergent AEs by 
maximum severity (i.e., CTCAE grade).  
All AEs, including treatment-emergent and non-treatment-emergent AEs, will be listed 
in patient data listings. 
11.5.7.2 
Laboratory Evaluations 
The parameters associated with the clinical laboratory tests (hematology, clinical 
chemistry, and urinalysis) will be summarized with descriptive statistics by visit and 


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for the change from baseline to each planned post-baseline visit, by group/tumor 
histology and overall. Listings of all laboratory results and reference ranges will be 
provided.  
Graded laboratory abnormalities will be defined using the grading scheme based on 
NCI CTCAE (v5.0) and summarized by group/tumor histology and overall. Shift tables 
will also be produced for gradable parameters based on the baseline CTCAE grade 
and the maximum CTCAE grade. 
11.5.7.3 
Other Safety Evaluations 
Changes in the patient’s ECOG status and vital sign parameters will be summarized 
by group/tumor histology and overall, and any abnormal values will be tabulated.  
Listings of all data related to the patient’s ECOG status, physical examination findings, 
vital signs and ECG will be provided. 
11.6 INTERIM ANALYSIS 
No formal interim analyses are planned. 
The data from Part A will be analyzed at the end of Part A, and the data from Part B 
will be analyzed at the end of Part B. 
11.7 CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED 
ANALYSIS 
Any change or addition to the protocol can only be made in a written protocol 
amendment that must be approved by the sponsor, the IRB/EC, and the Health 
Authorities.  
Changes to the statistical analyses will be documented in a SAP change log and in 
the clinical study report. 


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12 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
12.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS 
12.1.1 
Informed Consent Process 
12.1.1.1 
Consent and Other Informational Documents Provided to 
Patients 
Consent forms describing in detail the study drug, study procedures, and risks are 
given to the patient and written documentation of informed consent is required prior to 
performing any study-related assessment which isn’t standard of care. Consent forms 
will be reviewed and approved by the appropriate IRB/EC prior to being given to 
potential participants. 
12.1.1.2 
Consent Procedures and Documentation 
Informed consent is a process that is initiated prior to the patient agreeing to 
participate in the study and continues throughout the patient’s study participation. 
Consent forms will be approved by an Institutional Review Board (IRB) and the patient 
will be asked to read and review the document. The investigator or designee will 
explain the research study to the patient and answer any questions that may arise. A 
verbal explanation will be provided in terms suited to the patient’s comprehension of 
the purposes, procedures, and potential risks of the study and of their rights as a 
research participant. The patient will have the opportunity to carefully review the 
written consent form and ask questions prior to signing. The patient should have the 
opportunity to discuss the study with their family or surrogates and think about it prior 
to agreeing to participate. The patient will sign the informed consent document prior 
to any procedures being done specifically for the study. The patient must be informed 
that participation is voluntary and that they may withdraw from the study at any time, 
without prejudice. A copy of the informed consent document will be given to the patient 
for their records. The informed consent process will be conducted and documented in 
the source document (including the date), and the form signed, before the patient 
undergoes any study-specific procedures. The rights and welfare of the patient will be 
protected by emphasizing to them that the quality of their medical care will not be 
adversely affected if they decline to participate in the study. 
12.1.2 
Study Discontinuation and Closure 
It is agreed that for reasonable cause, either the investigator or the sponsor may 
temporarily suspend or prematurely terminate this study or the investigator’s 
participation in this study, provided a written notice is submitted at a reasonable time 


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in advance of intended suspension or termination. If discontinuation is by the 
investigator, notice is to be submitted to BioMed Valley Discoveries, Inc. If 
discontinuation is by the sponsor, notice will be provided to each investigator. If the 
study is suspended or prematurely terminated, the investigator will promptly inform 
the study patients, IRB, and the sponsor will provide the reason(s) for the suspension 
or termination. Study patients will be contacted, as applicable, and be informed of 
changes to the study visit schedule. 
If a severe local reaction or drug-related SAE occurs at any time during the study, the 
Safety Monitoring Committee will review the case immediately. 
If one or more patients at any dose level develop any of the following adverse events 
deemed to be possibly, probably or definitely related to ulixertinib by the investigator 
and/or medical monitor, based upon close temporal relationship or other factors, the 
study will be immediately suspended and no additional ulixertinib doses will be 
administered pending review and discussion of all appropriate study data by the SMC: 
• Death 
• Anaphylaxis (angioedema, hypotension, shock, bronchospasm, hypoxia, or 
respiratory distress) 
The study will not be restarted until all parties have agreed to the course of action to 
be taken and the Institutional Review Boards/Ethic Committees (IRBs/ECs) have been 
notified. 
12.1.3 
Confidentiality and Privacy 
Patient confidentiality and privacy is strictly held in trust by the participating 
investigators, their staff, and the sponsor and their interventions. This confidentiality 
is extended to cover testing of biological samples and genetic tests in addition to the 
clinical information relating to patients. Therefore, the study protocol, documentation, 
data, and all other information generated will be held in strict confidence. No 
information concerning the study or the data will be released to any unauthorized third 
party without prior written approval of the sponsor. 
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the sponsor, representatives 
of the IRB, or regulatory agencies may inspect all documents and records required to 
be maintained by the investigator, including but not limited to, medical records and 
pharmacy records for the patients in this study. The clinical study site will permit 
access to such records. 
The study patient’s contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will continue to be 


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kept in a secure location for as long a period as dictated by the reviewing IRB, 
Institutional policies, or sponsor requirements. 
Patient’s data collected on eCRFs during the trial will be documented in a deidentified 
fashion and the patient will only be identified by the patient number, and/or by the 
patient’s initials, if also required. The study data entry and study management 
systems used will be secured and password protected. If, as an exception, it is 
necessary for safety or regulatory reasons to identify the patient, all parties are bound 
to keep this information confidential. 
The investigator will guarantee that all persons involved will respect the confidentiality 
of any information concerning the trial patients. All parties involved in the study will 
maintain strict confidentiality to assure that neither the person nor the family privacy 
of a patient participating in the trial is violated. Likewise, the appropriate measures 
shall be taken to prevent access of non-authorized persons to the trial data. 
12.1.4 
Future Use of Stored Specimens and Data 
With the patient’s approval and as approved by local IRBs, de-identified biological 
samples will be stored for future analysis as warranted by the rapidly-advancing 
understanding in this field. During the conduct of the study, an individual patient can 
choose to withdraw consent to have biological specimens stored for future research. 
However, withdrawal of consent with regard to biological specimens’ storage may not 
be possible after the study is completed. 
Collected samples may be transferred for analysis to the sponsor, or to other 
laboratories working for the sponsor. 
Biological samples will be stored for the time established by regulatory requirements 
or destroyed after the final clinical study report has been finalized if storage is not 
required. There might be a new request for these samples to be used for purposes 
related to the quality assurance of the laboratory tests described in this protocol, in 
which case they will be used for this purpose. This may include the assessment of the 
quality of current tests, the maintenance or improvement of these tests, the 
development of new test methods for the markers described in this protocol, as well 
as making sure that new tests are comparable to previous methods and work reliably. 
If study results suggest that further investigations using stored biological samples are 
warranted, these tests might be carried out on an exploratory basis. In addition, 
biological samples may be used by the sponsor or their research partners for further 
research that is not related to the disease or the product under study. This testing will 
be done on anonymized samples (meaning that any identification linking the patient 
to the sample is destroyed). Patients will be asked to sign an additional, separate 


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consent form for this optional testing and refusal of consent will not affect their 
possibility of participating in the study. 
12.1.5 
Key Roles and Study Governance 
12.1.5.1 
Safety Oversight 
An internal Safety Monitoring Committee (SMC) will be set up to review the safety of 
ulixertinib as the study progresses. The SMC will consist of clinical investigators, the 
CRO medical monitor, and sponsor representatives. The SMC will review any AEs 
and SAEs that occur during the study and will examine the safety of ulixertinib, 
including toleration of the starting dose, dose interruptions, dose reductions, and 
toxicities that may occur in later cycles of treatment. 
The safety review will be performed at regular intervals, at least semi-annually to 
access safety and efficacy data. 
The entire study or treatment of individual patients may be stopped under defined 
circumstances as outlined in Section 9. 
12.1.5.2 
Independent Imaging Review  
In Part B only, a central imaging vendor selected by the sponsor will review 
radiological findings and determine response assessments (in accordance with 
RECIST 1.1). 
12.1.5.3 
Clinical Monitoring 
Site monitoring is conducted to ensure that the rights and well-being of trial patients 
are protected, that the reported trial data are accurate, complete, and verifiable, and 
that the conduct of the trial is in compliance with the currently approved 
protocol/amendment(s), with ICH GCP, and with applicable regulatory requirements. 
Monitoring standards require full verification for the presence of informed consent, 
adherence to the inclusion/exclusion criteria, documentation of SAEs, and the 
recording of primary efficacy and safety variables. Additional checks of the 
consistency of the source data with the eCRFs are performed according to the study-
specific monitoring plan. 
A clinical monitoring plan (CMP) will be developed by the sponsor’s CRO. 
During the course of the study, a site monitor will conduct routine site visits to review 
protocol compliance, compare eCRF entries with individual patient’s original source 
documents (accessed by the investigator), assess product accountability and ensure 
the study is conducted according to applicable regulatory requirements. The review of 


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the patient’s original medical records shall be performed in a manner which ensures 
patient confidentiality is maintained. 
The investigator shall permit the site monitor to review study data as frequently as 
deemed necessary to ensure that data are recorded in an adequate manner and that 
protocol adherence is satisfactory. 
The investigator may not enroll patients into the study until such time that an initiation 
visit, or with the agreement of the sponsor, attendance at the investigator meeting, 
has been performed by the site monitor to conduct a detailed training of the protocol 
and eCRF. 
12.1.5.4 
Quality Assurance and Quality Control 
Each clinical site will perform internal quality management of study conduct, data and 
biological specimen collection, documentation and completion. 
Quality control (QC) procedures will be implemented beginning with the data entry 
system and data QC checks that will be run on the database will be generated. Any 
missing data or data anomalies will be communicated to the site(s) for 
clarification/resolution. 
Following written SOPs, the monitors will verify that the clinical trial is conducted, data 
are generated, biological specimens are collected, documented (recorded), and 
reported in compliance with the protocol, ICH GCP, and applicable regulatory 
requirements.  
The investigational site will provide direct access to all trial related sites, source 
data/documents, and reports for the purpose of monitoring and auditing by the 
sponsor/sponsor’s designee, and inspection by local and regulatory authorities. Key 
trial personnel must be available to assist monitors during visits. 
12.1.6 
Auditing Procedure 
In addition to the routine monitoring procedures, the sponsor or the regulatory 
authority can conduct an audit or an inspection (during the study or after its 
completion) to evaluate compliance with the protocol and the principles of GCP. 
The investigator agrees that representatives of the sponsor and regulatory authorities 
will have direct access, both during and after the course of this study, to audit and 
review all study-relevant medical records. 


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12.1.7 
Data Handling and Record Keeping 
12.1.7.1 
Data Collection and Management Responsibilities 
Data collection is the responsibility of the clinical trial staff at the site under the 
supervision of the investigator. The investigator is responsible for ensuring the 
accuracy, completeness, legibility, and timeliness of the data reported. 
All source documents should be completed in a neat, legible manner to ensure 
accurate interpretation of data. 
Hardcopies of the study visit worksheets will be provided for use as source document 
worksheets for recording data for each patient enrolled in the study. Data recorded in 
the eCRF derived from source documents should be consistent with the data recorded 
on the source documents. All information on eCRFs must be traceable to source 
documents in the patient's file. Data without a written or electronic record will be 
defined before trial start and will be recorded directly on the eCRFs, which will be 
documented as being the source data. All data requested on the eCRF must be 
entered and all missing data must be accounted for. 
Clinical data and clinical laboratory data will be entered into a 21 CFR Part 11 
compliant electronic data capture system. The data system includes password 
protection and internal quality checks to identify data that appear inconsistent, 
incomplete, or inaccurate. Clinical data will be entered directly from the source 
documents. 
12.1.7.2 
Study Records Retention 
Study documents should be retained for a minimum of 2 years after the last approval 
of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or until at least 2 years have 
elapsed since the formal discontinuation of clinical development of the study drug. 
These documents should be retained for a longer period, however, if required by local 
regulations. No records will be destroyed without the written consent of the sponsor, 
if applicable. It is the responsibility of the sponsor to inform the investigator when these 
documents no longer need to be retained.  
Study documents include:  
• IRB/EC approvals for the study protocol and all amendments 
• All source documents and laboratory records 
• CRF copies (electronic copies on a CD-ROM) 
• Patients' informed consent forms (with study number and title of trial) 
• FDA form 1572 
• Any other pertinent study document 


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12.1.8 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, ICH GCP, or 
study manual requirements. The noncompliance may be either on the part of the 
patient, investigator, or the study site staff. As a result of deviations, corrective actions 
are to be developed by the site and implemented promptly. 
It is the responsibility of the investigator to use continuous vigilance to identify and 
report deviations. All deviations must be addressed in study source documents. 
Protocol deviations must be sent to the reviewing IRB per their policies. The 
investigator is responsible for knowing and adhering to the review IRB requirements. 
Further details about the handling of protocol deviations will be included in the study 
manual. 
12.1.9 
Publication and Data Sharing Policy 
An ICH-compliant integrated clinical and statistical report will be prepared upon 
completion of the study and data analysis. The results of the study may be published 
in a relevant peer-reviewed journal, with authorship status and ranking designated 
according to the acknowledged contributions of participating investigators, institutions, 
and the sponsor. 
All information provided to the investigator by BioMed Valley Discoveries, Inc., or their 
designee, will be kept strictly confidential. No disclosure shall be made except in 
accordance with a right of publication granted to the investigator. 
No information about this study or its progress will be provided to anyone not involved 
in the study other than by BioMed Valley Discoveries, Inc., or its authorized 
representatives, or in confidence to the IRB, or similar committee, except if required 
by law. 
12.1.10 Conflict of Interest Policy 
The independence of this study from any actual or perceived influence is critical. 
Therefore, any actual conflict of interest of person who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and 
managed. Furthermore, person who have a perceived conflict of interest will be 
required to have such conflicts managed in such a way that is appropriate to their 
participation in the design and conduct of this trial. 
12.1.11 Insurance 
The sponsor has established an insurance policy for the total anticipated duration of 
the study, covering the patients with respect to the risks involved in taking part in this 
study in accordance with this protocol. In the case of injury or disability deriving from 


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participation in the study, patients are requested to inform the investigator or their staff 
responsible for the study at the institution without delay. 
12.2 PROTOCOL AMENDMENT HISTORY 
Version 
Date 
Description of 
Change 
Brief Rationale 
 
 
 
 
 
 
 
 


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13 REFERENCES 
 
1. 
Dahlman et al, 2012. BRAFL597 Mutations in Melanoma Are Associated with Sensitivity to MEK 
Inhibitors. Cancer Discov September 1 2012 (2) (9) 791-797; DOI: 10.1158/2159-8290.CD-12-
0097. 
2. 
Dankner et al, 2018. Classifying BRAF alterations in cancer: new rational therapeutic strategies 
for actionable mutations. Oncogene 37, 3183–3199; DOI: 10.1038/s41388-018-0171-x. 
3. 
Dankner et al, 2018. Dual MAPK Inhibition Is an Effective Therapeutic Strategy for a Subset of 
Class II BRAF Mutant Melanomas. Clin Cancer Res December 15 2018 (24) (24) 6483-6494; 
DOI: 10.1158/1078-0432.CCR-17-3384. 
4. 
Davies et al, 2002. Mutations of the BRAF gene in human cancer. Nature, Jun 
27;417(6892):949-54. Epub 2002 Jun 9. DOI: 10.1038/nature00766. 
5. 
Emery et al, 2017. BRAF-inhibitor Associated MEK Mutations Increase RAF-Dependent and -
Independent Enzymatic Activity. Mol Cancer Res. Oct;15(10):1431-1444. DOI: 10.1158/1541-
7786.MCR-17-0211. 
6. 
Gao et al, 2018. Allele-specific mechanisms of activation of MEK1 mutants determine their 
properties. Cancer Discov. May;8(5):648-661. Epub 2018 Feb 26. DOI 10.1158/2159-8290.CD-
17-1452.  
7. 
Germann et al, 2017. Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical 
Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib). Mol Cancer Ther. 2017 
Nov;16(11):2351-2363. Epub 2017 Sep 22. DOI: 10.1158/1535-7163.MCT-17-0456. 
8. 
Houben et al, 2004. Constitutive activation of the Ras-Raf signaling pathway in metastatic 
melanoma is associated with poor prognosis. J Carcinog. 2004; 3: 6. Epub 2004 Mar 26. DOI: 
10.1186/1477-3163-3-6. 
9. 
Ikenoue et al, 2004. Different Effects of Point Mutations within the B-Raf Glycine-Rich Loop in 
Colorectal Tumors on Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase 
Kinase/Extracellular Signal-Regulated Kinase and Nuclear Factor κB Pathway and Cellular 
Transformation. Cancer Res May 15 2004 (64) (10) 3428-3435; DOI: 10.1158/0008-5472.CAN-
03-3591. 
10. Jones et al, 2017. Non-V600BRAF Mutations Define a Clinically Distinct Molecular Subtype of 
Metastatic Colorectal Cancer. JCO 35, no. 23 (August 10, 2017) 2624-2630. DOI: 
10.1200/JCO.2016.71.4394 
11. Mendzelevski et al, 2018. Effect of ulixertinib, a novel ERK1/2 inhibitor, on the QT/QTc interval 
in patients with advanced solid tumor malignancies. Cancer Chemother Pharmacol. 81(6):1129-
1141. 
12. Menzer et al, 2019. Targeted Therapy in Advanced Melanoma with Rare BRAF Mutations. JCO 
37, no. 33 (November 20, 2019) 3142-3151. DOI: 10.1200/JCO.19.00489. 
13. Santarpia et al, 2009. Detection and molecular characterization of a novel BRAF activated 
domain mutation in follicular variant of papillary thyroid carcinoma. Human Pathology, 40(6);827-
833. DOI: 10.1016/j.humpath.2008.11.003. 
14. Smalley et al, 2009. CRAF inhibition induces apoptosis in melanoma cells with non-V600E 
BRAF mutations. Oncogene, Jan 8;28(1):85-94. Epub 2008 Sep 15. DOI: 
10.1038/onc.2008.362. 
15. Sullivan et al, 2018. First-in-class ERK1/2 inhibitor ulixertinib (BVD-523) in patients with MAPK 
mutant advanced solid tumors: Results of a phase I dose-escalation and expansion 
study. Cancer Discov. 2018;8(2):184-195.  


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16. Wan et al, 2004.  Mechanism of activation of the RAF-ERK signaling pathway by oncogenic 
mutations of B-RAF. Cell, Mar 19;116(6):855-67. DOI: 10.1016/s0092-8674(04)00215-6. 
17. Yaeger et al, 2019.  Targeting Alterations in the RAF−MEK Pathway. Cancer Discov 
2019;9:329-341. Epub 2019 Feb 15. DOI: 10.1158/2159-8290.CD-18-1321. 
18. Yao et al, 2015. BRAF Mutants Evade ERK-Dependent Feedback by Different Mechanisms that 
Determine Their Sensitivity to Pharmacologic Inhibition. Cancer Cell, 2015. 28(3): p. 370-83. 
19. Yao et al, 2017. Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated 
RAS. Nature 548(7666): p. 234-238. 
 
 
 


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Appendix 1 
Non-Permitted Concomitant Medications 
 
1Ritonavir is usually given in combination with other anti-HIV or anti-HCV drugs in clinical practice. 
Caution should be used when extrapolating the observed effect of ritonavir alone to the effect of 
combination regimens on CYP3A activities. 
Strong inhibitors: ≥ 5-fold increase in AUC 
Strong inducers: ≥ 80% decrease in AUC 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-
substrates-inhibitors-and-inducers; Table 3.2 (inhibitors) and Table 3.3 (inducers), dated 12.03.19; 
Accessed 02.24.20 
 
 
INHIBITORS 
INHIBITORS 
INHIBITORS 
CYP1A2 
CYP2D6 
CYP3A 
ciprofloxacin 
bupropion 
boceprevir 
enoxacin 
fluoxetine 
clarithromycin 
fluvoxamine 
paroxetine 
cobicistat 
 
quinidine 
danoprevir/ritonavir1 
 
terbinafine 
elvitegravir/ritonavir1 
 
 
grapefruit juice 
INDUCERS 
 
idelalisib 
CYP3A 
 
indinavir/ritonavir1 
apalutamide 
 
itraconazole 
carbamazepine 
 
ketoconazole 
enzalutamide 
 
lopinavir/ritonavir1 
mitotane 
 
nefazodone 
phenytoin 
 
nelfinavir 
rifampin 
 
paritaprevir/ritonavir1 
St. John’s Wort 
 
posaconazole 
 
 
ritonavir 
 
 
saquinavir/ritonavir1 
 
 
telaprevir 
 
 
telithromycin 
 
 
tipranavir/ritonavir1 
 
 
troleandomycin 
 
 
voriconazole 


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Appendix 2 
List of Accepted Atypical BRAF Type II Alterations for 
Group 2  
BRAF Alteration 
Evidence of Pathway Activation 
(Reference Number) 
P367L/S 
17 
R462I 
2, 9, 16 
I463S 
2, 8, 15 
G464V/E/R 
2, 3, 4, 8, 9, 10, 16, 17, 18, 19 
F468C 
9 
N486_A489delinsK 
17 
N486_P490del 
17 
E586K 
2, 3, 4, 16, 17 
A598V 
2, 10, 13 
T599I/K/dup 
2, 15, 16, 17 
K601_S602delinsNT 
17 
K601E/N/T 
1, 2, 3, 10, 12, 16, 17, 18, 19  
A728V 
2, 16 
BRAF kinase duplication 
17 
BRAF fusions 
2, 3, 12, 17, 18, 19 
 
 
 
 


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Appendix 3 
ECOG Performance Status  
ECOG Performance Status 
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 house work, 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, confined 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 
 

SAP_001.pdf: 
 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 Final / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 1 of 44 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
 
SPONSOR: 
 
BioMed Valley Discoveries  
 
 
PROTOCOL NUMBER: 
 
BVD-523-ABC  
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
 
Author: 
David Manteigas  
Version: 
2.0 
Date: 
09-Jun-2023 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 Final / 09-Jun-2023 
 
Template Author: Andra Rusu 
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BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
1 Cover and signature pages 
 
Sponsor: 
BioMed Valley Discoveries 
Protocol Number: 
BVD-523-ABC 
Study Title: 
A Two-Part, Phase II, Multi-center Study of the ERK Inhibitor 
Ulixertinib (BVD-523) for Patients with Advanced Malignancies 
Harboring MEK or Atypical BRAF Alterations 
Document Version No 
2.0 
 
We, the undersigned, confirm that we have read, understood and agree to the content of this 
document and hereby authorise its approval. 
Statistician 
Name and Date are not required if electronic signatures are used. Do not resize boxes.  
Name 
Title 
[text box when using 
eSignatures]: 
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Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 Final / 09-Jun-2023 
 
Template Author: Andra Rusu 
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BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
Client Representative 
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eSignatures]: 
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Senior Scientist
President


 
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2 Table of Contents 
 
1 
Cover and signature pages ...................................................................................................... 2 
2 
Table of Contents .................................................................................................................... 4 
3 
List of Abbreviations ................................................................................................................ 6 
4 
Introduction ............................................................................................................................. 8 
5 
Study Objectives ...................................................................................................................... 8 
6 
Study Design .......................................................................................................................... 10 
6.1 
STUDY DESIGN AND POPULATION ................................................................................ 10 
6.2 
STUDY TREATMENTS AND ASSESSMENTS ..................................................................... 12 
6.3 
RANDOMIZATION AND BLINDING ................................................................................. 13 
6.4 
SAMPLE SIZE JUSTIFICATION ......................................................................................... 13 
7 
Statistical Considerations ...................................................................................................... 14 
7.1 
STUDY TREATMENT ....................................................................................................... 14 
7.2 
PLANNING OF ANALYSES ............................................................................................... 14 
7.3 
STUDY AND ANALYSIS PERIODS ..................................................................................... 15 
7.4 
SOFTWARE ..................................................................................................................... 15 
7.5 
MISSING DATA HANDLING ............................................................................................ 15 
7.6 
PARTIAL DATE IMPUTATION .......................................................................................... 16 
7.7 
VISIT WINDOWING ........................................................................................................ 17 
7.8 
REPORTING GUIDELINES ................................................................................................ 18 
8 
Analysis Sets .......................................................................................................................... 21 
9 
Methods of Analyses and Presentations ............................................................................... 22 
9.1 
PATIENT DISPOSITION ................................................................................................... 22 
9.2 
PROTOCOL DEVIATIONS AND/OR VIOLATIONS ............................................................. 22 
9.3 
DEMOGRAPHIC AND BASELINE CHARACTERISTICS ....................................................... 23 
9.4 
MEDICAL HISTORY AND CONCOMITANT DISEASES ....................................................... 24 
9.5 
PRIOR THERAPIES .......................................................................................................... 24 
9.6 
STUDY DRUG EXPOSURE AND/OR COMPLIANCE .......................................................... 26 
9.7 
PHARMACOKINETIC/ PHARMACODYNAMIC ENDPOINTS AND ANALYSES .................... 27 
9.7.1 
Pharmacokinetic Data ........................................................................................... 27 
9.7.2 
Pharmacodynamic Data ........................................................................................ 27 
9.8 
EFFICACY DATA ENDPOINTS AND ANALYSES ................................................................ 27 
9.8.1 
Overall Response Rate (ORR) / Best Overall Response (BOR) ................................ 27 
9.8.2 
Duration of Response (DOR) .................................................................................. 30 
9.8.3 
Progression-free Survival (PFS) .............................................................................. 31 
9.8.4 
Overall Survival (OS) .............................................................................................. 31 
9.9 
SAFETY DATA ENDPOINTS AND ANALYSES .................................................................... 32 
9.9.1 
Adverse Events (AEs) .............................................................................................. 32 
9.9.2 
Clinical Safety Laboratory Evaluation .................................................................... 34 
9.9.3 
Other Safety data .................................................................................................. 34 
10 
Interim Analyses ................................................................................................................ 36 


 
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11 
Changes to Planned Analyses ............................................................................................ 36 
12 
Document History.............................................................................................................. 37 
13 
References ......................................................................................................................... 37 
14 
Appendices ........................................................................................................................ 38 
14.1 
Schedule of events ........................................................................................................ 38 
14.2 
CTCAE v5.0 Grading for Laboratory Values ................................................................... 43 
 


 
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3 List of Abbreviations  
AE 
Adverse Event 
ATC 
Anatomical Therapeutic Chemical Classification 
BOR 
Best Overall Response 
BRAF 
V-raf murine sarcoma viral oncogene homolog B1 
BVD 
BioMed Valley Discoveries 
CI 
Confidence interval 
CM 
Concomitant medications 
CR 
Complete Response 
CRA 
Clinical Research Associates 
CRC 
Colorectal cancer 
CRO 
Clinical Research Organization 
DBP 
Diastolic blood pressure 
DOR     
Duration of response 
EAS 
Evaluable Analysis Set 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Form 
ERK 
Extracellular signal-regulated kinase 
FAS 
Full Analysis Set 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IRB 
Institutional Review Boards 
IxRS 
Interactive Voice/Web Response System 
MedDRA 
Medical Dictionary for Regulatory Activities 
MEK 
Mitogen-activated protein kinase/extracellular signal-related kinase 
mRNA 
Messenger ribonucleic acid 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
ORR 
Overall Response Rate 
OS 
Overall survival 
PD 
Pharmacodynamic 
PDCF 
Protocol Deviation Criteria Form 


 
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PFS 
Progression Free Survival 
PK 
Pharmacokinetic 
PP 
Per-protocol analysis set 
PR 
Partial Response 
PT 
Preferred Term 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SBP 
Systolic blood pressure 
SMC 
Safety Monitoring Committee 
SOC 
System Organ Class 
TEAE 
Treatment Emergent Adverse Event 
TFLs 
Tables, listings and figures 
WHO 
World Health Organization 


 
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4 Introduction 
The purpose of this document is to describe the statistical methods, data derivations and data 
summaries to be employed in the analysis of the Phase II study titled “A Two-Part, Phase II, Multi-
center Study of the ERK Inhibitor Ulixertinib (BVD-523) for Patients with Advanced Malignancies 
Harboring MEK or Atypical BRAF Alterations”. This study, set up by BioMed Valley Discoveries, 
aims at evaluating the safety and clinical benefit of ulixertinib as measured by the overall response 
rate (ORR) in patients receiving ulixertinib that have advanced malignancies harboring a MEK or 
atypical BRAF alteration. The study has two parts, Part A, aiming at assessing the clinical benefit 
of ulixertinib, followed by Part B, in patients with selected tumor types. The study will also include 
an initial assessment of the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of 
ulixertinib in patients.  
This statistical analysis plan (SAP) covers the final analysis for both Part A and Part B of the study. 
Given that Part B is dependent upon Part A results, this version of the SAP will focus mostly on 
Part A analysis and a new version will be prepared to further detail Part B analysis once Part A 
analysis is complete. The list of tables, figures and listings (TFLs) to be developed for each analysis, 
as well as the shells for each TFL, are described in a separate document. 
The preparation of this SAP is based on study Protocol version 1.0 from 01JUN2021, the most up 
to date electronic Case Report Form (eCRF) version and on the International Conference on 
Harmonization (ICH) E3 and E9 Guidelines. 
 
5 Study Objectives 
The primary, secondary, and exploratory objectives along with the associated endpoints as per 
the study protocol are presented as follows: 
Part A – Tumor Histology Agnostic 
Primary Objective 
 
To assess the clinical benefit of ulixertinib as measured by the overall response rate (ORR) 
in patients receiving ulixertinib that have advanced malignancies harboring a MEK or 
atypical BRAF alteration. 
Primary Endpoint 
 
ORR will be defined as the percentage of patients achieving a Best Overall Response (BOR) 
of confirmed Complete Response (CR) and/or Partial Response (PR), according to RECIST 
1.1. 
Secondary Objectives 


 
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 
To evaluate the safety profile of ulixertinib. 
 
To assess the duration of response (DOR). 
 
To assess the progression free survival (PFS) and overall survival (OS) over 18 months. 
 
To measure the blood levels of ulixertinib and selected metabolites. 
Secondary Endpoints 
 
Safety profile, including term, incidence, severity, and duration of AEs, as per CTCAE v5.0. 
 
DOR according to RECIST 1.1. 
 
PFS time according to RECIST 1.1. 
 
OS time. 
 
Pharmacokinetic profile of ulixertinib (BVD-523) and selected metabolites. 
Exploratory Objectives 
 
To evaluate the effects of ulixertinib on pharmacodynamic markers. 
Exploratory Endpoint 
 
ctDNA, tissue biopsies, and/or blood to access biomarkers. Assays include, but are not 
limited to, phosphorylation of RSK from whole blood, RPPA to assess protein levels, e.g. 
DUSP 4/6, plus Nanostring and/or RNA-exome to assess mRNA expression in tissue pre- 
and post-ulixertinib treatment. 
 
 
Part B – Tumor Histology Specific 
Primary Objective 
 
To assess PFS in patients receiving ulixertinib in defined tumor histologies (up to three 
histologies to be selected) compared to physician’s choice of treatment. Patient’s tumors 
must harbor a specified MEK or atypical BRAF alteration. 
Primary Endpoint 
 
PFS will be defined as the time from first day of trial medication to disease progression 
according to RECIST 1.1, or death. 
Secondary Objectives 
 
To evaluate the safety profile of ulixertinib. 
 
To assess OS over 18 months in patients receiving ulixertinib with a defined tumor 
histology and specified MEK or atypical BRAF alteration, compared to physician’s choice 
of treatment. 


 
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 
To determine the ORR and DOR in patients receiving ulixertinib with a defined tumor 
histology and a MEK or atypical BRAF alteration, according to RECIST 1.1, compared to 
physician’s choice of treatment. 
Secondary Endpoints 
 
Safety profile, including term, incidence, severity, and duration of AEs, as per CTCAE v5.0. 
 
OS time. 
 
ORR and DOR according to RECIST 1.1. 
 
6 Study Design 
6.1 
STUDY DESIGN AND POPULATION 
This is a two-part, phase II, multicenter study of the ERK inhibitor ulixertinib (BVD-523) with an 
open-label, tumor histology agnostic part (Part A) and a tumor histology specific part (Part B). 
 
Part A: Tumor Histology Agnostic 
 
Part A of the study will be open label and enroll patients to one of six groups based on their tumor 
alteration: 
 
 
Group 1: Patients with tumors, other than colorectal cancer (CRC), having a BRAF 
alteration that results in an amino acid change at positions G469, L485, or L597. 
 
Group 2: Patients with tumors, other than CRC, having a defined Class 2 BRAF alteration. 
 
Group 3: Patients with tumors, other than CRC, having an atypical BRAF alteration (non 
V600) that is not specified in Group 1 or Group 2. 
 
Group 4: Patients with CRC having any atypical BRAF alteration. 
 
Group 5: Patients with tumors, other than CRC, harboring alterations in MEK1/2. 
 
Group 6: Patients with CRC harboring alterations in MEK1/2. 
 
Part B: Tumor Histology Specific 
Part B of the study will randomly enroll patients with one of up to three specified tumor 
histologies to receive either ulixertinib or the physician’s choice of treatment in a 2:1 ratio. 
Tumors must harbor a specified MEK or atypical BRAF alteration. If a patient progresses on 
physician’s choice of treatment, crossover to the ulixertinib arm is permitted.   
An overview of the study design is presented in  Figure 1 below. 
 


 
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Figure 1. Study Design 
 
 
 
 
 
 
 
 
 
 
 
Group 1 (n=38)
•
Alterations at BRAF-G469, -
L485, or -L597
•
Any histology (excluding CRC)
Group 2 (n=38)
•
Defined class II BRAF 
alterations (see appendix 2)  
•
Any histology (excluding CRC)
Group 3 (n=38)
•
Any other atypical BRAF 
alteration
•
Any histology (excluding CRC)
Group 4 (n=38)
•
Any atypical BRAF alteration
•
CRC patients only
Group 5 (n=38)
•
MEK1/2 alteration
•
Any histology (excluding CRC)
Group 6 (n=38)
•
MEK1/2 alteration
•
CRC patients only
PART A
Ulixertinib 600 mg BID
PART B
Defined histology and alterations determined by Part A 
Randomized: Ulixertinib 600 mg BID or Physician's choice
1: Defined histology and alterations
Ulixertinib 600 mg BID
Physician’s choice
2: Defined histology and alterations
Ulixertinib 600 mg BID
Physician’s choice
3: Defined histology and alterations 
Ulixertinib 600 mg BID
Physician’s choice
2:1
2:1
2:1


 
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Ongoing data from Part A will also be used to prioritize one or more tumor histologies that warrant 
study in Part B. The specific histologies and alterations to be included in Part B will be selected 
based on available data from Part A and discussion with the clinical investigators, the medical 
monitor, and the sponsor. 
Part A of the study will enroll approximately 228 patients with 38 patients per group. Additional 
patients may be enrolled as appropriate. Part B of the study will enroll 80-100 patients per 
histology, with up to three histologies included, additional patients may also be enrolled. 
The estimated duration of accrual is 21 months. The total duration of the study will be 
approximately 38 months. 
Patients are considered to have completed the study if they have completed all phases of the 
study including the last visit or the last scheduled procedure.  
Patients will continue on study therapy until documented disease progression, intolerable toxicity, 
study closure, or until other treatment discontinuation criteria is met. Patients who discontinue 
study therapy prior to disease progression, will continue to be followed for progression, survival 
or initiation of subsequent anticancer therapy for 18 months from the date of study therapy 
initiation. It is estimated that participants will be on study for up to 30 months.  
Screen failures are defined as patients who consent to participate in the clinical trial but do not 
meet the criteria required for participation in the trial during the screening procedures. Patients 
who do not meet the inclusion criteria may be rescreened and will be assigned a new subject 
identification number. 
 
6.2 
STUDY TREATMENTS AND ASSESSMENTS  
Patients will receive 600 mg oral doses of ulixertinib, which is to be taken twice daily (b.i.d.) orally 
for 28 days, at 12-hour ± 2 hours intervals, approximately the same time each day with food and 
at least 8 ounces of water. Patients will be provided the study drug for a full cycle to self-
administer at home. 
Patients experiencing unacceptable toxicity will have their treatment interrupted until the toxicity 
returns to ≤ Grade 1 or pre-treatment baseline. Dose adjustments will be done in consultation 
with the investigators and medical monitor of the study. If a non-treatment related adverse event 
(AE) or toxicity-related dose delay lasts for > 21 days, treatment will be discontinued permanently, 
and the patient will be removed from study treatment. 
 


 
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6.3 
RANDOMIZATION AND BLINDING 
Part A is designed as an open-label study. All patients in Part A will receive treatment with orally 
administered ulixertinib. Patients in Part B will receive either treatment with orally administered 
ulixertinib or the physician’s choice of treatment in a 2:1 ratio. In Part B, if a patient progresses 
on the physician’s choice of treatment then they may crossover to the ulixertinib arm. 
Part B randomization will be performed as total enrollment rather than on a site basis.  
Randomization/enrollment in both parts will be performed by using Interactive Voice/Web 
Response System (IxRS). In Part B, the IxRS will randomly assign the patient to one of the two 
treatment arms (ulixertinib or the physician’s choice of treatment). In both parts, the IxRS will 
assign the patient a unique patient identification number. This patient identification number will 
then be reported on all eCRF pages and in any study documents. 
 
6.4 
SAMPLE SIZE JUSTIFICATION 
Part A 
Approximately 38 patients will be recruited into each group in Part A. 
With 34 patients in a group and assuming the true ORR is 40%, there is approximately 80% power 
to reject the null hypothesis that the true ORR is ≤ 20% in that group, with a 1-sided alpha of 5%. 
Assuming a 10% drop out rate, up to 38 patients will be recruited in each group. 
Part B 
Part B sample size estimation may be updated after Part A results are available. 
Approximately 80-100 patients will be randomized, using a 2:1 ratio, for each histology group in 
Part B.  
Using a 2-sided, log-rank test with a 5% alpha, and assuming a median PFS of 1.7 to 8.5 months 
(depending on histology) in the physician’s choice arm and twice as long on the ulixertinib arm, 
approximately 80 to 100 patients will be required in each group to achieve 80% power to show a 
statistically significant difference between the arms. This also assumes that each group will take 
approximately 24 months to accrue, and the analysis is expected to be performed 18 months 
following the last patient accrued. The anticipated loss to follow-up is estimated to be 10%. 
 


 
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7 Statistical Considerations 
7.1 
STUDY TREATMENT 
The study drug is ulixertinib (BVD-523). The study treatment refers to treatment with ulixertinib 
(BVD-523). For Part B, the physician’s choice treatment will be provided to patients in the 
comparator arm. 
 
7.2 
PLANNING OF ANALYSES 
This SAP covers final analysis for Part A and Part B, although the analysis for Part B will be further 
described once Part A results are available in an updated SAP version. The planned timing of 
analysis for Part A is 18 months after the last patient enrolled starts treatment. Since Part B 
depends on Part A results it is not possible to estimate by when Part B analysis will occur. The SAP 
will be updated after Part A results are available and the Protocol is amended. 
Given that the study was early terminated during Part A, an abbreviated CSR focusing on safety 
will be prepared. Therefore not all Tables, Listings and Figures planned in SAP version 1 will be 
required. The Shells table of contents will have an additional column to indicate which outputs 
will be delivered for the final analysis of Part A. 
 
 
 


 
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7.3 
STUDY AND ANALYSIS PERIODS 
Study periods are summarized in Table 1 below. Analysis periods will mirror these periods and are 
summarized in Table 2 below. 
Table 1. Study periods 
Period 
Visit 
Planned days  
Part A and Part B 
SCREENING 
Screening (up to 4 weeks 
before Baseline) 
Day -28 to Day -1 
TREATMENT 
  
  
  
  
Cycle 1 
Baseline 
Day 8 ± 3   
Day 15 ± 3 
Cycle 2  
Day 29 ± 3 
Day 36 ± 3 
Day 43 ± 3 
Cycle 3 – Cycle n 
Day 57 ± 3 – Day n ± 3 
FOLLOW-UP 
End of Treatment (EOT) Visit 
≤14 ± 3 days after last dose 
Safety Follow-Up 
30 ± 3 days after last dose 
Follow-Up 
Every three months (± 7 days) until death, end of the study, 
or patient withdrawal of consent, whichever comes first. 
 
Table 2. Analysis periods 
Phase  
Period 
Definition 
Part A and 
Part B 
PRE-TREATMENT 
From informed consent form (ICF) signature to the day before first dose of 
study treatment. 
ON-TREATMENT 
From the day of first dose of study treatment to ≤14 ± 3 days after last dose 
of study treatment (date of EOT visit), or the earliest date of subsequent 
anti-cancer drug therapy – 1 day, whichever occurs first. 
FOLLOW-UP 
From day ≤14 ± 3 after last dose of study treatment, or the earliest date of 
subsequent anti-cancer drug therapy, whichever occurs first, to end of 
study. End of study is date of completion / discontinuation from the study 
as collected in the CRF or the last recorded assessment in the database if 
the patient has not completed/discontinued the study at the time of the 
analysis. 
 
7.4 
SOFTWARE 
The SAS Viya version 3.5 (or higher), will be used for all analysis, unless otherwise specified. 
 
7.5 
MISSING DATA HANDLING 
No imputation for missing data will be carried out other than to complete partial dates using 
standard imputation techniques as described below in Section 7.6. 


 
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7.6 
PARTIAL DATE IMPUTATION 
Detailed rules for partial date imputation are described below.  
A permanent new date variable should be created if there is a requirement to be used in 
determining flags (such as on-treatment flags), sort orders and other derived variables needed for 
a table, listing, or figure. Imputed date variable names will be defined in the derived dataset 
specifications. 
Original (raw) date variables must not be overwritten. Imputed dates will not be displayed in the 
listings. 
General rules for Adverse events (AE) and prior and concomitant medications (CM) 
In case of partial dates with missing day:  
For AE and CM, any partial start date during the month of first dosing will be imputed to be the 
date of first dose, taking the worst-case scenario.  
For any AE and CM starting after the month of first dosing, the start date will be imputed to be 
the first day of the month.  
For any AE and CM starting before the month of first dosing, the start date will be imputed to be 
the last day of the month.  
Partial AE and CM end dates will be imputed to be the last day of the month or at the date of 
study discontinuation/completion, whichever occurs first.  
In case of partial dates with missing day and missing month:  
For AE and CM, any partial start date during the year of first dosing will be imputed to be the date 
of first dose, taking the worst-case scenario.  
For any AE and CM starting after the year of first dosing, the start date will be imputed to be the 
first day of the year (i.e. 01 January).   
For any AE and CM started before the year of first dosing, the start date will be imputed to be the 
last day of the year (i.e. 31 December).  
Partial AE and CM end dates will be imputed to be the last day of year (i.e. 31 December) or at 
the date of study discontinuation/completion, whichever occurs first.    
Some examples are given below (DDMMMYYYY).  


 
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In most cases, start dates are imputed as first day of the month or first of January.  
Table 3: Examples of missing dates imputation 
Data Type 
Start 
Date 
Imputed 
Start Date 
First Dose 
date 
End Date 
Imputed End 
Date 
Adverse Event, 
Prior/Concomitant Meds 
JAN2017 
31JAN2017 
11NOV2017 
MAR2017 
31MAR2017 
Adverse Event, 
Prior/Concomitant Meds 
MAR2017 
01MAR2017 
27JAN2017 
MAR2017 
31MAR2017 
Adverse Event, 
Prior/Concomitant Meds 
2017 
27JAN2017 
27JAN2017 
2017 
16MAR2017£ 
Adverse Event, 
Prior/Concomitant Meds 
MAR2017 
01MAR2017 
27JAN2017 
MAR2017 
01MAR2017* 
Adverse Event, 
Prior/Concomitant Meds 
JAN2017 
31JAN2017 
27FEB2017 
2017 
31DEC2017 
£ Patient discontinued on 16MAR2017; * Patient discontinued on 01MAR2017. 
Rules for other partial dates 
Partial dates are not expected for death. However, should a partial date be present for death, the 
date will be imputed to be the day after the last visit/assessment date when the patient was 
known to be alive, if there is at least one visit/assessment during the month of the corresponding 
partial death date. If there is no visit/assessment performed during the month of the 
corresponding partial death date, then the partial death date would be imputed as the first day 
of the month. A similar approach will be followed for partial date for death in which only year is 
known. 
If partial date is present for dates related to disease history, the same rules as for AE and CM will 
be applied. 
 
7.7 
VISIT WINDOWING 
Planned assessments will not be re-assigned to any planned visits using statistical programming 
based on assessment date. All the data will be analysed according to the planned visit as collected 
in the eCRF. Data obtained at unscheduled and repeat assessments will be considered for the 
derivation of baseline, worst on-treatment result for safety analyses (clinical safety laboratory 
evaluation, other safety data), and time to event analyses. 
 


 
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7.8 
REPORTING GUIDELINES 
Visit labels  
The visit labels displayed in Table 4 will be used to display results in the TFLs. Following Cycle 2, 
any subsequent Cycle will consider Day 1 as start of Cycle and not the days since first study dose 
as for Cycle 2. 
Table 4. Visit Labels 
Period 
Visit  
TFLs Label 
Part A and Part B 
Screening: Day -28 to Day -1 
Screening Day -28 to Day -1 
Screening 
Cycle 1 
Cycle 1 Day 1  
Baseline 
Cycle 1 Day 8  
C1D8  
Cycle 1 Day 15 
C1D15 
Cycle 2 
Cycle 2 Day 29 
C2D29 
Cycle 2 Day 36 
C2D36 
Cycle 2 Day 43 
C2D43 
Cycle 3 
Cycle 3 Day 1 
C3D1 
… 
… 
… 
Cycle n 
Cycle n Day 1 
CnD1 
End of Treatment: ≤14 ± 3 days after last dose of 
study treatment. 
End of Treatment Visit 
EOT 
Safety Follow-Up: 30 ± 3 days after last dose of 
study treatment. 
Safety Follow-Up 
SFU 
Follow-Up: every three months (± 7 days) until 
death, end of the study, or patient withdrawal of 
consent, whichever comes first. 
Follow-Up 
FUn 
Summaries of baseline and change from baseline 
Baseline and change from baseline will be calculated for all assessments, including additional 
assessments (if applicable), as follows: 
 
Baseline is defined as the last available assessment prior to first dose of study treatment, 
including additional assessments (where applicable). Assessments that occurred on the 
same day as first dose, when time of assessment is not available, will be assumed to be 
prior to first dose (unless the assessment is planned after first dose in the protocol).  
 
Change from baseline will be calculated as the difference between the post-baseline 
assessment value and the baseline value. 


 
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Whenever applicable, percent change from baseline will be calculated as the difference between 
the post-baseline assessment value and baseline value divided by the baseline value multiplied 
by 100. 
Unscheduled visit / Repeat assessments 
Data obtained at unscheduled and repeat assessments will be considered for the derivation of 
baseline, worst on-treatment result for safety analyses (clinical safety laboratory evaluation, 
other safety data), and time to event analyses.  
All other data from unscheduled or repeat assessments will not be included in summaries and will 
only be presented in data listings, if not otherwise specified. 
N 
N will be the number of patients in the specified population and group. 
Summary presentation  
For Part A all outputs will be presented by molecular alteration group as defined in SAP section 
6.1 and overall if not otherwise specified. For Part B, all outputs will be presented by the selected 
histology groups, physicians choice of treatment (pooling all treatments under just one group) 
and overall. 
Continuous data  
Continuous data will be summarized using number of patients (n), mean, standard deviation, 
median, first and third quartiles (Q1 and Q3), minimum value, and maximum value.  
Categorical data  
Categorical data will be summarized using n and percentage.   
 
All categories will be presented, even if no patients are counted in a particular category, 
unless otherwise stated. 
 
A Missing category will be displayed in all tables for categories where at least one missing 
value exists, unless otherwise specified. 
 
Counts of zero in any category will be presented without percentage.  
 
All summary percentages will be calculated using N, unless otherwise stated in a footnote. 
 
For AEs, medical history, prior and concomitant medications, the counts are based on 
single counts of patients with multiple events/treatments under the same category, while 
the percentages are calculated using N. Counts will be displayed by descending order of 
frequency for the overall group by dictionary hierarchy. 
 


 
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Precision of summary statistics 
 
Integer – Sample size (n, N) and number of missing data (if displayed). 
 
One additional decimal place than reported/collected – Mean, median, other percentile, 
confidence interval. 
 
Two additional decimal places than reported/collected – Standard deviation. 
 
Same number of decimal places as reported/collected – Minimum, maximum. 
 
Percentages – One decimal place.  
Study day  
Study day will be calculated as (assessment date – date of first study treatment dose) for pre-
baseline assessments and [(assessment date – date of first study treatment dose) + 1] for post-
baseline assessments, i.e. there will be no study day 0 and study day 1 will correspond to the first 
study treatment dose. 
Ordering  
Data will be presented in listings in order of group, patient ID, visit, assessment date/time, and 
assessment type/parameters chronological order unless otherwise specified. In case of clinical 
laboratory results, the listings will be presented in order of group, patient ID, parameter, 
assessment date/time, visit. 
Date format 
Dates will be presented in format DDMMMYYYY. 
Dictionaries 
Latest version of Medical Dictionary for Regulatory Activities (MedDRA) will be used for the 
relevant outputs.  
Latest version of World Health Organization (WHO) Drug Global B3 will be used for the relevant 
outputs.  
NCI-CTCAE v5.0 will be used for the relevant outputs.  
The version will be documented in the footnote of the corresponding TFLs. 
File naming  
Each TFL output file will be named with a t, l, or f added before the TFL number to denote the 
output type and then according to its table numbering in the following way: Table 14.2-1.1 would 
be t14_2_1_1, Table 14.2-11 would be t14_2_11, Listing 16.2.7-1.1 would be l16_2_7_1_1, and 
Figure 14.2-2.1 would be f14_2_2_1. 


 
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Reporting guidelines 
 
Page Orientation: Landscape. 
 
Tables and listings: will be created in .rtf.  
 
Figures: will be generated directly in .rtf. 
 
Font: Courier New font with minimum of 8-point font size. 
 
Margins: Left: 3.8 cm, Right: 2 cm, Top: 3 cm, Bottom: 2 cm, on letter paper. 
 
Columns header will be left aligned for listings. 
8 Analysis Sets 
All Patients Analysis Set 
All Patients Set will include all patients who were enrolled (signed informed consent) regardless 
of whether they received the study drug or not. 
Full Analysis Set 
The full analysis set (FAS) will consist of all patients who received at least one dose of study drug. 
This analysis set will be used for all efficacy analyses. 
For Part B, analyses performed on the FAS will allocate patients’ treatment group as randomized. 
Safety Analysis Set 
The safety analysis set will consist of all patients who received at least one dose of study drug. 
This analysis set will be used for all safety analyses. 
For Part B, analyses performed on the safety population will allocate patients’ treatment group 
as actually received. 
Per Protocol Analysis Set 
The per-protocol analysis set (PP) will consist of all patients of the FAS who completed the study 
without any important protocol deviations. Prior to any analysis, all patients with important 
protocol deviations will be reviewed and a decision can be made to include a patient in PP even 
when there is at least one important protocol deviation. Those cases, if any, will be properly 
documented in the study report. 
Evaluable Analysis Set 
The Evaluable Analysis Set (EAS) will consist of patients from FAS who had the first efficacy 
evaluation on Study Day 29+3. Prior to any analysis, all patients data will be reviewed and 
additional criteria for exclusion from EAS may be added (e.g. occurrence of one or more important 
protocol deviations). Those cases, if any, will be properly documented in the study report. 


 
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For Part A the Full Analysis Set and the Safety Full Analysis Set will be the same. Given that the 
study was early terminated and an abbreviated CSR focusing mostly on safety data will be 
prepared, EAS and PP will not be used in any analysis. 
 
9 Methods of Analyses and Presentations 
9.1 
PATIENT DISPOSITION  
The patient disposition data will be presented by group and overall, for both Part A and Part B on 
the All Patients Analysis Set. The number and percentage of patients belonging to the following 
disposition modalities will be presented along with the reason for discontinuation: patients 
enrolled, patients eligible for inclusion in the study, patients completed/discontinued screening, 
patients completed/discontinued treatment, patients completed/discontinued study. 
The number and percentage of patients in each analysis set will also be presented. 
A consort diagram with disposition information will also be provided. 
In addition, information on analysis sets, study completion and discontinuation, informed consent 
and failed inclusion and exclusion criteria will be listed. 
For Part B, a listing of randomization will be presented.  
 
9.2 
PROTOCOL DEVIATIONS AND/OR VIOLATIONS 
ICH E3 Q&A R1 defines a protocol deviation as “any change, divergence, or departure from the 
study design or procedures defined in the protocol”, and important protocol deviations as “a 
subset of protocol deviations that may significantly impact the completeness, accuracy, and/or 
reliability of the study data or that may significantly affect a patient's rights, safety, or well-being”. 
The non-compliance may be either on the part of the patient, the investigator, or the study site 
staff. The list of potential protocol deviations, including classification (Important/Non-important) 
for each protocol deviation, will be pre-defined in the Protocol Deviation Criteria Form (PDCF). 
Protocol deviations identified during the trial by the Clinical Research Associates (CRAs), Medical 
Monitors, or Data Managers will be tracked throughout the study using a protocol deviation 
tracker and classified as Important/Non-important. All protocol deviations will be read into SAS® 
prior to reporting. 
Prior to data lock for the primary and final analyses, a review classification meeting will be held 
to review protocol deviations and classifications, and to agree on the final analysis sets. 


 
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Important protocol deviations will be summarized (frequencies and percentages) by deviation 
category and summary term for both Part A and Part B on FAS. 
A listing of all protocol deviations will be provided for all patients. 
 
9.3 
DEMOGRAPHIC AND BASELINE CHARACTERISTICS 
The following demographic and baseline characteristics will be summarized using descriptive 
statistics and presented by group and overall, for both Part A and Part B, on the FAS: 
 
Age at screening (years), as derived in the eCRF - continuous and categorical using 
EudraCT categorization (18-64, 65-84, ≥ 85) 
 
Gender 
 
Childbearing/Reproductive potential 
 
Ethnicity 
 
Race 
 
Height at screening (cm) 
 
Weight at screening (kg) 
 
BMI at screening (kg/m^2)  
 
ECOG performance status at screening 
 
Smoking history  
 
Gene (BRAF, MEK1/MAP2K1, MEK2/MAP2K2)  
 
Codon as reported in the eCRF 
 
Amino acid change as reported in the eCRF 
 
NGS Vendors 
The following disease history characteristics will be summarized using descriptive statistics and 
presented by group and overall, for both Part A and Part B, on the FAS: 
 
Cancer Diagnosis (only reported diagnosis will be displayed, not all categories displayed 
in the CRF) 
 
Time since initial diagnosis (in months) 
 
Disease stage at initial diagnosis (from 1 to 4) 
 
Disease stage at enrollment (from 1 to 4) 
 
Method of diagnosis (cytological/histological) 
 
Prior Cancer Therapies/Regimens (Yes/No) 
 
Prior BRAF/MEK Inhibitor Therapies (Yes/No) 
 
Prior Radiation Therapies (Yes/No) 
Time since initial diagnosis will be calculated as [(date of first dose of study treatment - date of 
diagnosis) / 30.4375]. 
In addition, listings of the above data will be produced for all patients. 


 
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A by-patient, detailed listing of smoking history will be also presented. 
 
9.4 
MEDICAL HISTORY AND CONCOMITANT DISEASES 
Medical history and concomitant diseases will be coded using MedDRA. 
Medical histories are defined as events reported on the Medical History and Disease History eCRF 
pages, which started before the first study treatment date and were not ongoing at the first study 
treatment date.  
Concomitant diseases are defined as diseases which started before the first study treatment date 
but were ongoing at the first study treatment date. 
The number and percentage of patients with a medical history will be tabulated by group and 
overall, for both Part A and Part B, by system organ class (SOC) and preferred term (PT) on the 
Safety Analysis Set. A by-patient listing will be produced. 
The number and percentage of patients with a concomitant disease will be tabulated by group 
and overall, for both Part A and Part B, for each SOC and PT using the FAS. A by-patient listing will 
be produced. 
 
9.5 
PRIOR THERAPIES 
The following summaries will be created by group and overall, for both Part A and Part B, on the 
FAS: 
Prior radiotherapy:  
 
Received at least one prior radiotherapy 
 
Site of prior radiotherapies (only reported sites will be displayed, not all categories 
displayed in the eCRF) 
 
Most recent therapy received before study treatment start: duration of therapy (months) 
and site 
For prior radiotherapy, duration in months will be calculated as [(end date of therapy – start date 
of therapy) + 1] / 30.4375. 
Prior Anti-Cancer Therapies:  
 
Received at least one prior anti-cancer therapy 
 
Lines of prior anti-cancer therapies 
 
Most recent therapy received before study treatment start: regimen name, BOR, duration 


 
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of therapy (months), time since BOR, time since relapse/progression, and reason for 
discontinuation. 
Prior BRAF/MEK inhibitor therapies:  
 
Received at least one prior BRAF/MEK inhibitor therapy 
 
Most recent therapy received before study treatment start: treatment name, BOR, 
duration of BOR, duration of therapy (months), and reason for discontinuation. 
For prior anti-cancer therapies, duration in months will be calculated as [(end date of therapy - 
start date of therapy) + 1] / 30.4375. 
Time since BOR (months) will be calculated as [(date of first study treatment - date of BOR)+1] / 
30.4375.  
Time since relapse/progression (months) will be calculated as [(date of first study treatment - date 
of Relapse/Progression) + 1] / 30.4375. 
For prior BRAF/MEK inhibitor therapies, duration in months will be calculated as [(end date of 
therapy - start date of therapy) + 1] / 30.4375.  
Prior and Concomitant Medication:  
Medications other than the study treatment will be coded using the WHO Drug Global dictionary. 
The version of the dictionary will be provided in the corresponding TFLs footnotes.   
Medications will be defined as follows: 
 
Prior Medication: any medications whose end date is before the first study treatment 
date.  
 
Concomitant Medication: any medications whose start or end date is either the same or 
after the first dose of study treatment and up to the end of the on-treatment period. 
- 
Any medication with a missing medication end date will be assumed to be 
concomitant medication.  
- 
Ongoing medications are considered as concomitant medications. 
The number and percentage of patients with prior and concomitant medications will be tabulated 
by group and overall, for both Part A and Part B, by Anatomical Therapeutic Chemical 
Classification (ATC) and preferred term (PT) on the FAS. A by-patient listing will be produced for 
prior and concomitant medications as well as for all prior therapies. 
On treatment Radiation, Surgery and Medical Procedures, and Blood Transfusions: 
On treatment Radiation, Surgery and Medical Procedures, and Blood Transfusions will be listed 
on the FAS. 


 
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9.6 
STUDY DRUG EXPOSURE AND/OR COMPLIANCE 
Duration on treatment and cumulative dose received will be calculated for ulixertinib as defined 
below. 
Part A  
 
Number of cycles received = 
Number of cycles where the patient received at least one dose. 
 
 
Duration of exposure (months) =  
[(Date of last known treatment dosing with ulixertinib – date of initial dosing with 
ulixertinib) + 1] / 30.4375 
 
 
Planned cumulative dose (mg) =  
Number of cycles received x 28 x 2 x 600. 
 
 
Actual cumulative dose received (mg) =  
Sum of [(number of capsules dispensed – number of capsules returned) x 150]. 
 
 
Relative dose intensity =  
100 x Actual dose intensity / Planned dose intensity, with: 
o Actual dose intensity (mg/day) = Actual cumulative dose received (mg) / Duration 
of exposure (days). 
o Planned dose intensity (mg/day) = Planned cumulative dose (mg) / Duration of 
exposure (days). 
Summary statistics will be presented for the number of cycles received, duration of exposure, 
actual cumulative dose, and relative dose intensity, by group and overall for Part A on the FAS. 
The number and percentage of patients having at least one dosing interruption or adjustment will 
be tabulated with the corresponding reason by group and overall for Part A on the FAS. A by-
patient listing will be produced. 
Part B study drug exposure and compliance will be further described in an updated SAP version 
once Part A results are available.  
 


 
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9.7 
PHARMACOKINETIC/ PHARMACODYNAMIC ENDPOINTS AND ANALYSES 
9.7.1 Pharmacokinetic Data 
Blood samples will be collected when the patient is at steady state (patients who have received 
at least 5 days, or 10 consecutive doses, of investigational product) to measure ulixertinib and 
selected metabolites plasma concentrations. Plasma concentration will be listed and summarized 
by analyte and visit including the Geometric mean and Coefficient of Variation. All data will be 
listed but tables will only include data that was collected when ulixertinib was at steady state as 
required by protocol. 
9.7.2 Pharmacodynamic Data 
Blood samples will be collected pre-dose and 4 hours +/- 10 minutes post-dose on cycle 1 day 1, 
and cycle 1 day 15 to measure phosphorylation of ERK1/2 target RSK (pRSK). Percent inhibition of 
pRSK  compared to baseline will be listed and summarized.   
 
9.8 
 EFFICACY DATA ENDPOINTS AND ANALYSES  
All efficacy analyses will be performed on the FAS and replicated on PP and EAS as supportive 
analysis for Part B. For Part A only FAS and EAS will be used for efficacy analysis. 
All efficacy data will be presented by group and overall, for both Part A and Part B, unless 
otherwise specified in the specific section. 
 
9.8.1 Overall Response Rate (ORR) / Best Overall Response (BOR) 
Tumor response will be assessed by the Investigator using RECIST 1.1 criteria1.  
The decision for body areas to be scanned will depend on the extent of disease. Tumor 
assessments must include all known or suspected disease sites. Imaging will be performed on the 
abdomen, chest, pelvis, and the site of the primary tumor if elsewhere. Tumor measurements 
based on physical examination will occur at baseline and on the first day of each treatment cycle. 
Tumor assessments will be made by CT/MRI/Physical Exam prior to dose initiation, at the 1st 
protocol-specified tumor measurement evaluation at the beginning of Cycle 2 and then every 2 
cycles, and at End of Treatment. Patients that discontinue study treatment for any reason other 
than disease progression, must continue to have disease assessments every 8 weeks (± 7 days) 
until disease progression or the initiation of subsequent anticancer therapy. The schedule of 
tumor assessments should be fixed according to the calendar, starting with cycle one day one, 
regardless of treatment delays or interruptions due to toxicity. The same imaging technique used 
to characterize each identified and reported lesion at baseline will be employed in the following 
tumor assessments. 


 
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Anatomical measurements (target lesions) will be documented during screening and each 
subsequent evaluation. Objective assessments will be performed during screening and before the 
first study drug dose of every other cycle, starting with cycle 2.  
The table below provides a summary of the overall response status determination at each time 
point. 
  Table 5. Evaluation of Overall Response 
Target lesions 
Non-target lesions 
New lesions 
Overall response 
CR 
CR (or no non-target lesions) 
No 
CR 
No target lesion a 
CR 
No 
CR 
CR 
NE b 
No 
PR 
CR 
Non-CR/non-PD 
No 
PR 
PR 
Non-PD and NE (or no non-target lesions) b 
No 
PR 
SD 
Non-PD and NE (or no non-target lesions) b 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
No target lesion a 
Not all evaluated 
No  
NE 
No target lesion a 
Non-CR/non-PD 
No 
Non-CR/non-PD 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
No target lesion a 
Unequivocal PD 
Yes or No 
PD 
No target lesion a 
Any 
Yes 
PD 
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease, and NE = not 
evaluable. 
a Defined as no target lesion at baseline. 
b Not evaluable is defined as when either no or only a subset of lesion measurements is made at an assessment. 
The ORR is defined as the percentage of patients having a confirmed response of either CR or PR. 
ORR will be calculated with the 95% confidence intervals (CIs). The 95% CIs will be estimated using 
the Clopper-Pearson method. 
For Part B, ORR will be compared between ulixertinib and physician’s choice of treatment using a 
Chi square test or Fisher’s exact test as applicable. 
Complete and partial response must be confirmed by a repeat assessment performed at > or = 4 
weeks after the criteria for response are first met. Date of confirmed CR/PR will be the date of the 
first CR/PR that qualifies for confirmation. Additionally, patients with no post-baseline efficacy 
measurement due to reasons accountable for disease progression, will be assessed as non-
evaluable and will count in the denominator of the ORR. 
BOR will be assessed based on the tumor response at different evaluation time points from 
baseline until the first documented disease progression for RECIST or the last response 
assessment if there is no document disease progression at the time of the analysis. The order 
used to determine BOR is CR>PR>SD>PD, ignoring visits with missing tumor assessments. For SD 
to qualify for BOR, the SD assessment should be at least 6 weeks after first ulixertinib dose. BOR 


 
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date in this case will be the date of the first SD/PR/CR documented after 6 weeks. 
The following table, based on Table 3 from the RECIST 1.1 guidelines1, summarizes the algorithm 
describing how confirmed response and BOR are determined from the overall tumor assessments.  
Table 6. Evaluation of Confirmed BOR 
Case 
Overall 
response 
first timepoint 
Overall response 
subsequent 
timepoint 
Confirmed response/BOR 
1 
CR 
CR 
CR (if assessments at least 28 days apart). (note: sequence of CR – 
NE – CR would be considered as confirmed CR) 
2 
CR 
PR 
SD, PD, or PR 
 
If CR truly met at first timepoint, any subsequent assessment 
of PR should make the disease PD at that point. That is, 
neither a PR nor SD may follow CR. 
 
Therefore, SD, if CR assessment >=6 weeks (42 days after date 
of first treatment), otherwise PD. 
 
However, BOR may be PR if subsequent scans suggest small 
lesions were still present at first assessment (in which case 
first assessment of CR should be changed to PR) 
3 
CR 
SD 
SD or PD 
 
SD, if CR or SD assessment >=6 weeks (42 days) after date of 
first treatment,  
otherwise PD 
4 
CR 
PD 
SD or PD 
 
SD, if CR assessment >=6 weeks (42 days after date of first 
treatment),  
otherwise PD 
5 
CR 
NE 
SD or NE 
 
SD, if CR assessment >=6 weeks (42 days after date of first 
treatment 
otherwise NE  
6 
PR 
CR 
PR (if assessments at least 28 days apart). 
7 
PR 
PR 
PR (if assessments at least 28 days apart). (note: sequence of PR – 
NE – PR would be considered as confirmed PR) 
Where there are cases of more than one SD assessment between 
two PR assessments, then this should be discussed. 
8 
PR 
SD 
SD 
9 
PR 
PD 
SD or PD 
 
SD, if PR assessment >=6 weeks (42 days after date of first 
treatment),  
otherwise PD 
10 
PR 
NE 
SD or NE 
 
SD, if PR assessment >=6 weeks (42 days after date of first 
treatment),  
otherwise NE 
11 
SD 
SD, PR, CR 
SD 
12 
SD 
PD 
SD or PD 
 
SD, if SD assessment >=6 weeks (42 days after date of first 
treatment),  
otherwise PD 


 
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Case 
Overall 
response 
first timepoint 
Overall response 
subsequent 
timepoint 
Confirmed response/BOR 
13 
SD 
NE 
SD or NE 
 
SD, if SD assessment >=6 weeks (42 days after date of first 
treatment),  
otherwise NE 
14 
NE, - 
SD 
SD 
15 
CR, PR, SD 
- 
SD or NE 
 
SD, if assessment >=6 weeks (42 days after date of first 
treatment) and does not qualify for CR or PR,  
otherwise NE. 
16 
PD 
 
PD. Ignore all assessments after initial overall response of PD.  
17 
NE 
NE 
NE 
Where all assessments are Not evaluable 
For changes in target tumor size, spider and waterfall plots will be presented. For all response 
assessments, swimmer plots will be presented. Target and Non-Target Lesions response 
assessments and incidence of new lesions will be summarized by visit and listed. All response 
assessments will be listed. 
9.8.2 Duration of Response (DOR) 
The duration of response (in months) is defined as the period from the date of initial confirmed 
PR or CR until the date of first radiographically documented progressive disease or death from 
any cause. Only patients with BOR of CR or PR (i.e. responders) will be included in the analysis of 
duration of response. 
DOR = [(Date of first PD/death – Date of first recorded confirmed CR/PR) + 1] / 30.4375 
Patients with no documented progression or death after CR or PR will be censored at the last 
available tumor assessment (last assessment that is CR, PR, or SD): 
       DOR = [(Date of last assessment – Date of first recorded CR/PR) + 1] / 30.4375 
The analysis of DOR will be performed with a Kaplan-Meier method (product-limit estimates) and 
a summary of associated statistics will be presented including corresponding two-sided 95% CI. 
The CI for the median will be calculated according to Brookmeyer and Crowley and CI for the 
survival function estimates at Month 3, 6, 9, 12, and 18 will be derived using the log-log 
transformation (SAS PROC LIFETEST CONFTYPE=LOGLOG), only if there are sufficient data for 
responders. However, the final choice of timepoints may be updated dependent upon the data. 
Part B, DOR will be compared between ulixertinib and physician’s choice of treatment using a Log 
Rank test or other appropriate test if the proportional hazards assumption does not hold. 
 


 
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9.8.3 Progression-free Survival (PFS)  
The PFS (in months) is defined as the time from the first ulixertinib dose until the first 
radiographically documented progression of disease or death from any cause, whichever occurs 
first. 
       PFS = [(Date of first PD/death – Date of first study treatment) + 1] / 30.4375 
Patients with no documented progression or death will be censored at the last available tumor 
assessment (last assessment that is CR, PR or SD): 
        PFS = [(Date of last assessment where patient is PD free – Date of first study treatment) + 1] 
/ 30.4375 
For patients with no post baseline tumor assessment a censored PFS at day 1 will be considered. 
        PFS = (Date of first study treatment – Date of first study treatment) + 1 
The analysis of PFS will be performed with a Kaplan-Meier method (product-limit estimates) and 
a summary of associated statistics will be presented including corresponding two-sided 95% CI. 
The CI for the median will be calculated according to Brookmeyer and Crowley and CI for the 
survival function estimates at Month 3, 6, 9, 12, and 18 will be derived using the log-log 
transformation (SAS PROC LIFETEST CONFTYPE=LOGLOG). However, the final choice of timepoints 
may be updated dependent upon the data. 
For Part B, for each histology, PFS curves will be compared between ulixertinib and physician’s 
choice of treatment using Log Rank Test or other appropriate test if the proportional hazards 
assumption does not hold.  
 
9.8.4 Overall Survival (OS)  
 
The OS (in months) is defined as the time from first treatment to death. Patients who did not die 
during the study will be censored at the last known alive date. 
 
                  OS = [(Date of death – Date of first study treatment) + 1] / 30.4375 
 
For censored patients: 
 
                 OS = [(Last known alive date – Date of first study treatment) + 1] / 30.4375 


 
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The last known alive date will be determined among study treatment administrations, any visits 
where at least one assessment has been completed, or any follow-up assessment where the 
patient has been confirmed to be alive. 
OS will be analyzed using the same Kaplan-Meier method used to analyze the DOR. 
Part B, OS will be compared between ulixertinib and physician’s choice of treatment using a Log 
Rank Test or other appropriate test if the proportional hazards assumption does not hold. 
 
9.9 
SAFETY DATA ENDPOINTS AND ANALYSES 
All safety analyses will be performed on the Safety Analysis Set using descriptive statistics.  
All safety data will be presented by group and overall, for both Part A and Part B, unless otherwise 
specified in the specific section. 
9.9.1 Adverse Events (AEs) 
The following definitions will be used: 
 
Treatment-emergent AEs (TEAEs): Treatment-emergent adverse event (TEAE) is defined 
as any AE that emerges during on-treatment period, after the 1st dose of the study agent. 
 
Related AEs: AEs suspected by the Investigator and/or Sponsor to have a relationship to 
study treatment (as recorded on the AE eCRF page, Causality = Related, Possibly Related, 
or missing). 
 
Serious Adverse Events (SAE): serious AEs (as recorded on the AE eCRF page, Does AE 
Meet the Definition of an SAE = Yes).  
 
AEs leading to treatment discontinuation: AEs leading to permanent discontinuation of 
study treatment (as recorded on the AE eCRF page, Action taken with study treatment = 
Drug withdrawn).  
 
AEs leading to dose reduction: AEs leading to dose reduction of study treatment (as 
recorded on the AE eCRF page, Action taken with study treatment = Dose Reduced).  
 
AEs leading to treatment interruption: AEs leading to treatment interruption of study 
treatment (as recorded on the AE eCRF page, Action taken with study treatment = Drug 
Interrupted).  
 
AEs leading to Death: adverse event leading to death (as recorded on the AE eCRF page, 
Results in death, or Outcome = Fatal, or Grade = 5).  
An overview summary table will present the number and percentage of patients with a TEAE, 
including: 
 
TEAEs / TEAEs related to study treatment 


 
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 
SAEs / SAEs related to study treatment  
 
TEAEs leading to treatment discontinuation / TEAEs related to study treatment leading to 
treatment discontinuation 
 
TEAEs leading to treatment discontinuation within 1 cycle / TEAEs related to study 
treatment leading to treatment discontinuation within 1 cycle 
 
TEAEs leading to treatment discontinuation following 1 cycle / TEAEs related to study 
treatment leading to treatment discontinuation following 1 cycle 
 
TEAEs leading to treatment interruption / TEAEs related to study treatment leading to 
treatment interruption 
 
TEAEs leading to treatment interruption within 1 cycle / TEAEs related to study treatment 
leading to treatment interruption within 1 cycle 
 
TEAEs leading to treatment interruption following 1 cycle / TEAEs related to study 
treatment leading to treatment interruption following 1 cycle 
 
TEAEs leading to dose reduction / TEAEs related to study treatment leading to dose 
reduction  
 
TEAEs leading to dose reduction within 1 cycle / TEAEs related to study treatment leading 
to dose reduction within cycle 1 
 
TEAEs leading to dose reduction following 1 cycle / TEAEs related to study treatment 
leading to dose reduction following cycle 1 
 
TEAEs leading to death / TEAEs related to study treatment leading to death 
 
TEAEs with grade ≥ 3 / TEAEs related to study treatment with grade ≥ 3 
In addition, the following tables will be produced by SOC and PT: 
 
TEAEs / TEAEs related to study treatment 
 
Serious TEAEs / Serious TEAEs related to study treatment 
 
TEAEs and maximum CTCAE grade / TEAEs related to study treatment and maximum 
CTCAE grade 
 
TEAEs leading to treatment within/following discontinuation / TEAEs related to study 
treatment leading to treatment discontinuation 
 
TEAEs leading to treatment within/following interruption / TEAEs related to study 
treatment leading to treatment interruption 
 
TEAEs leading to dose reduction within/following cycle 1 / TEAEs related to study 
treatment leading to dose reduction within/following cycle 1 
 
TEAEs leading to death / TEAEs related to study treatment leading to death 
The following tables will be produced by PT: 
 
TEAEs / TEAEs related to study treatment 
 
Serious TEAEs / Serious TEAEs related to study treatment 
A patient with multiple occurrences of an AE will be counted only once in the AE category. SOCs 
will be sorted by descending order of frequency for the overall group, PTs will be sorted by 
descending order of frequency for the overall group within each SOC. 


 
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All deaths will be summarized and listed with the corresponding reasons, split by overall deaths, 
and deaths occurring after the first dose of ulixertinib. 
The following listings will be provided: 
 
All AEs 
 
TEAEs 
 
SAEs 
 
Deaths 
 
9.9.2 
Clinical Safety Laboratory Evaluation 
All haematology, biochemistry, and urinalysis laboratory tests collected will be reported.  
The numerical measurements and change from baseline of all haematology, biochemistry, and 
urinalysis laboratory tests will be summarized using descriptive summary statistics for each visit. 
For laboratory tests covered by the NCI-CTCAE (version 5), laboratory data will be graded 
accordingly. ‘Normal’ will be assigned for all non-missing values not graded as 1 or higher. For 
laboratory tests where grades are not defined by NCI-CTCAE, results will be graded by the 
low/normal/high classifications based on laboratory normal ranges as collected in the CRF. 
Separate tables will be created for Gradable and Non-gradable laboratory values. 
Haematology and biochemistry laboratory tests will be summarized by: 
 
Tables (Gradable and Non-gradable) to describe the worst on-treatment value by cycle. 
 
Shift tables (Gradable and Non-gradable) to compare baseline to the worst on-treatment 
value. 
Listings of all laboratory data with values flagged to show the corresponding NCI-CTCAE grades 
and the classifications relative to the laboratory normal ranges will also be provided. Also results 
of serum pregnancy tests will be listed. 
9.9.3 Other Safety data 
9.9.3.1  Vital signs 
Vital signs include the following parameters: systolic blood pressure (SBP) (mmHg), diastolic blood 
pressure (DBP) (mmHg), pulse (beats/min), and temperature (°C). 
The numerical measurements and change from baseline of all vital signs parameters will be 
summarized using descriptive summary statistics for each visit. 


 
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Shift tables of baseline to worst on-treatment result (low, normal, high, very high) will be 
presented. 
Table 7. Thresholds for classification of vital signs test results 
Vital Sign 
Criteria 
Flag 
Temperature 
< 36.4°C 
Low 
36.4°C – 37.7°C 
Normal 
> 37.7°C 
High 
Pulse 
< 55 bpm 
Low 
55-100 bpm 
Normal 
101-150 bpm 
High 
> 150 bpm 
Very High 
Systolic Blood 
Pressure 
< 90 mmHg 
Low 
90-130 mmHg 
Normal 
131-160 mmHg 
High 
≥ 161 mmHg 
Very High 
Diastolic Blood 
Pressure 
< 60 mmHg 
Low 
60-85 mmHg 
Normal 
86-100 mmHg 
High 
≥ 101 mmHg 
Very High 
All Vital Signs will be Listed. 
 
9.9.3.2 Electrocardiogram (ECG) 
ECG includes the following parameters: Heart Rate (beats/min), PR Interval (msec), QRS Duration 
(msec), RR Interval (msec), QT Interval (msec), and QT interval corrected for heart rate by the 
Fridericia’s formula (QTcF) Interval (msec). 
The numerical measurements at baseline of all ECG parameters will be summarized using 
descriptive summary statistics. 
A listing of ECG evaluations will be created. 
 
9.9.3.3 ECHO/MUGA 
ECHO/MUGA assessments at baseline will be summarized using descriptive summary statistics. 
A listing of ECHO/MUGA evaluations will be created. 
 
 


 
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9.9.3.4 Physical Examination  
Physical Examination includes the following parameters: HEENT, Thorax, Abdomen, Skin and 
Mucosae, Neurological, Extremities, Urogenital, General Appearance, Heart, Back, and Lymph 
Nodes. 
All physical examination assessments at baseline will be summarized using descriptive summary 
statistics. 
A listing of physical examination evaluations will be created. 
 
9.9.3.5 Ophthalmology exam 
A listing of ophthalmological examination assessments will be created. 
 
9.9.3.6 ECOG Performance status 
The number and percentages of patients will be tabulated for ECOG performance score categories 
at each visit.  
 
A listing of all ECOG Performance status at all visits will be presented. 
 
10 Interim Analyses 
No interim analysis is planned. The outputs provided for the regular SMC data reviews are covered 
in a separate SAP. 
 
11 Changes to Planned Analyses 
No major changes to analyses planned in the protocol are expected.  
A new analysis population was defined to further investigate efficacy. Although the SAP will be 
signed and finalized prior to the first study analysis, this new analysis population is for exploratory 
purposes only. 
Demographic and baseline data was planned in the Protocol to be reported for all analysis 
populations. However, at least for Part A, this will only be reported on FAS. For Part B, this may 


 
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be revised and additional tables may be added for each analysis set. 
 
12 Document History 
Date 
Version 
Modified by 
Brief details of changes made to template 
20Dec2021 
1.0 
David Manteigas 
First SAP Version. 
09Jun2023 
2.0 
David Manteigas 
Updated version of the SAP to cover for the 
dry-run comments and to account for the 
required updates due to the study being 
early terminated. 
 
13 References 
1. Eisenhauer EA, Therasse P, Bogaerts J, et al. (2009), New response evaluation criteria in 
solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer; 45:228-47. 
 


 
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14 Appendices 
14.1 
Schedule of events 


 
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Table 14.1 
Part A and B: Schedule of Activities 
 
 
Cycle 1 
Day 1 through 28 
Cycle 2 
Day 29 through 56 
Cycle 3-X 
28-day cycles, visit on 
1st day of cycle 
Post Treatment Period 
Visit 
1 
Screening 
2 
Baseline 
3 
Tx 
4 
Tx 
5 
Tx 
6 
Tx 
7 
Tx 
8 
 -X Tx 
End of Treatment 
(EOT) Visit 
Safety Follow-
Upa 
Follow-
Upb 
Visit Day 
-28 to -1 
1 ± 0 
8 ± 3 
15 ± 3 
29 ± 3 
36 ± 3 
43 ± 3 
57 ± 3 
<14 ± 3 days 
after last dose 
30 ± 3 days 
after last dose 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
Medical historyc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Cancer historyd 
X 
 
 
 
 
 
 
 
 
 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Measure height  
X 
 
 
 
 
 
 
 
 
 
 
Measure weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Physical examinatione 
X 
 
 
 
 
 
 
 
 
 
 
ECOG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Ophthalmology examf 
X 
 
 
 
 
 
 
 
 
 
 
Pregnancy testg,h 
X 
Xg 
 
 
Xh 
 
 
Xh 
Xh 
 
 
Clinical lab testsi, j 
X 
Xi 
X 
X 
X 
X 
X 
Xj 
X 
 
 
Electrocardiogram (ECG)k 
X 
 
 
 
 
 
 
 
 
 
 
ECHO cardiogram or MUGA 
X 
 
 
 
 
 
 
 
 
 
 


 
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Table 14.1 
Part A and B: Schedule of Activities 
 
 
Cycle 1 
Day 1 through 28 
Cycle 2 
Day 29 through 56 
Cycle 3-X 
28-day cycles, visit on 
1st day of cycle 
Post Treatment Period 
Visit 
1 
Screening 
2 
Baseline 
3 
Tx 
4 
Tx 
5 
Tx 
6 
Tx 
7 
Tx 
8 
 -X Tx 
End of Treatment 
(EOT) Visit 
Safety Follow-
Upa 
Follow-
Upb 
Assess current disease 
statusl 
X 
 
 
 
X 
 
 
X 
X 
 
Xm 
Study drug administrationn 
 
X 
 
X 
 
 
 
 
 
 
 
Adverse events (AEs) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Obtain unused drug 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Compliance by pill count 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Study drug dispensed 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Part A Only 
Tissue biopsy, if indicatedo,p 
Xo 
 
 
 
X 
 
 
 
Xp 
 
 
Pharmacodynamic blood 
samplesq 
 
X 
 
X 
 
 
 
 
 
 
 
ctDNAr 
 
X 
 
X 
X 
 
 
 
X 
 
 
Pharmacokinetic sampless 
 
 
 
Xs 
 
 
 
 
 
 
 
Part B Only 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
Table footnotes: 
a 
Patients will return to the clinic or will be contacted for a safety follow-up assessment 30 days ± 3 days after the last dose of study drug was 
taken; or earlier if subsequent therapy for advanced malignancy is initiated prior to 30 days ± 3 days.   
 


 
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b 
Patients or their legally authorized representatives will be contacted every three months (± 7 days) until death, end of the study, or patient 
withdrawal of consent, whichever comes first. Survival and subsequent treatment status may be collected by public records, medical 
records, or by contacting the patient or their legally authorized representative by phone. 
c 
Full medical history at screening, only review/update of history at subsequent visits. 
d 
Oncologic history of the malignancy under study including prior regimens (duration of therapy, best response on therapy, date of 
discontinuation, and reason for discontinuation), surgery, and radiation therapy. 
e 
Physical examinations should be symptom driven after the Screening Visit. 
f 
Ophthalmological examinations will be performed by an ophthalmologist at screening, and whenever clinically indicated. In Part B, only 
patients in the ulixertinib arm need an ophthalmological exam. See section 10.1.5 for a full description of tests.  
g 
ONLY if the screening serum pregnancy test was performed more than 1 day previously. 
h 
After screening and baseline, if urine pregnancy test is positive, confirm with serum test. 
i 
Visit 2 clinical lab samples should be collected pre-dose if not done during Screening Visit within 72 hours of start of treatment. 
j 
Chemistry, hematology, and urinalysis. After Cycle 2, clinical labs to be performed prior to starting each new cycle or more frequently when 
clinically indicated at the investigator’s discretion. See section 10.1.6 for a full description of test.  
k 
Patients with a normal ECG in Cycle 1 do not need to have repeat ECGs in subsequent cycles. Patients should be supine for 5 minutes prior to 
the ECG. 
l 
Tumor assessments will be made prior to dose initiation, at Visit 5, and then every 2 cycles. Patients who discontinue treatment for reasons 
other than progression will have assessments at the EOT visit (unless their previous assessment was performed within 28 days). The same 
imaging modality used for an individual patient (i.e. CT or MRI) at Screening should be maintained throughout the study. 
m 
Patients that discontinue study treatment for any reason other than disease progression, must continue to have disease assessments every 8 
weeks (± 7 days) until disease progression or the initiation of subsequent anticancer therapy. 
n 
Study drug to be taken twice daily. The first dose should be taken in the clinic on days when PD sampling occurs i.e., Cycle 1/Visit 2 (Day 1) 
and Cycle 1/Visit 4 (Day 15), remaining doses on all other days to be self-administered by patient. 
o 
Tissue biopsy for Part A only. If a patient has undergone a biopsy within ≤ 6 months and has not received any anticancer treatment since 
undergoing the biopsy, archival tissue from this biopsy may be used to fulfill screening tissue requirements. 
p 
Tissue biopsy at final study visit/at progression is optional, but strongly encouraged to help elucidate mechanism of resistance. 
q 
Collect pre-dose and 4 hour +/- 10 mins post-dose blood samples for PD. 


 
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r 
Collect plasma for ctDNA.  
s 
Sample for PK should be collected pre-dose trough at steady state (patients who have received at least 5 days, or 10 consecutive doses, of 
study drug). 


 
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14.2 
CTCAE v5.0 Grading for Laboratory Values 
Table 8.  Hematology Tests 
Parameter 
CTCAE Gradable† 
SOC 
CTCAE v5.0 Term 
Hematocrit 
No 
 
 
Hemoglobin 
Yes 
Blood and lymphatic 
system disorders 
Anemia 
 
 
Investigations 
Hemoglobin increased 
Platelets 
Yes 
Investigations 
Platelet count decreased 
White blood cells 
Yes 
Investigations 
White blood cell decreased 
Blood and lymphatic 
system disorders 
Leukocytosis 
Red blood cell count 
No 
 
 
Neutrophils absolute 
Yes 
Investigations 
Neutrophil count decreased 
Lymphocytes absolute 
Yes 
Investigations 
Lymphocyte count decreased 
Lymphocyte count increased 
Monocytes absolute 
No 
 
 
Eosinophils absolute 
No 
 
 
Basophils absolute 
No 
 
 
† For laboratory tests where grades are not defined by NCI-CTCAE, results will be graded by the low/normal/high classification based 
on laboratory normal ranges. 
Table 9.  Serum Chemistry Tests 
Parameter 
CTCAE Gradable† 
SOC 
CTCAE v5.0 Term 
Albumin 
Yes 
Metabolism and 
nutrition disorders 
Hypoalbuminemia 
Alkaline phosphatase 
Yes 
Investigations 
Alkaline phosphatase increased 
ALT 
Yes 
Investigations 
Alanine aminotransferase 
increased 
AST 
Yes 
Investigations 
Aspartate aminotransferase 
increased 
Blood urea nitrogen 
No 
 
 
Uric acid 
No 
 
 
Chloride 
No 
 
 
Cholesterol 
Yes 
Metabolism and 
nutrition disorders 
Hypercholesterolemia 
Hypocholesterolemia 
Calcium 
Yes 
Metabolism and 
nutrition disorders 
Hypocalcemia  
Hypocalcemia  
Creatinine 
Yes 
Investigations 
Creatinine increased 
Lactate Dehydrogenase 
Yes 
Investigations 
Lactate Dehydrogenase increased 
Glucose 
Yes 
Metabolism and 
nutrition disorders 
Hyperglycemia 
Hypoglycemia 
Potassium 
Yes 
Hyperkalemia 


 
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Parameter 
CTCAE Gradable† 
SOC 
CTCAE v5.0 Term 
Metabolism and 
nutrition disorders 
 
Hypokalemia 
Sodium 
Yes 
Metabolism and 
nutrition disorders 
 
Hypernatremia 
Hyponatremia 
Inorganic Phosphorus 
No 
 
 
Total bilirubin 
Yes 
Investigations 
Blood bilirubin increased 
Triglycerides 
Yes 
Metabolism and 
nutrition disorders 
 
Direct bilirubin 
No 
 
 
Total protein 
No 
 
 
† For laboratory tests where grades are not defined by NCI-CTCAE, results will be graded by the low/normal/high classification based 
on laboratory normal ranges. 
Table 20.  Urinalysis Tests 
Parameter 
CTCAE Gradable† 
SOC 
CTCAE v5.0 Term 
Dipstick Evaluation Of 
Bilirubin 
No 
 
 
Dipstick Evaluation Of 
Blood 
No 
 
 
Dipstick Evaluation Of 
Glucose 
No 
 
 
Dipstick Evaluation Of 
Ketones 
No 
 
 
Dipstick Evaluation Of 
Leukocytes 
No 
 
 
Dipstick Evaluation Of 
Protein 
No 
 
 
Microscopic 
Examination Of Casts 
No 
 
 
Microscopic 
Examination Of Rbc 
No 
 
 
Microscopic 
Examination Of Wbc 
No 
 
 
pH 
No 
 
 
Specific Gravity 
No 
 
 
† For laboratory tests where grades are not defined by NCI-CTCAE, results will be graded by the low/normal/high classification based 
on laboratory normal ranges. 
 


 
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SPONSOR: 
 
BioMed Valley Discoveries  
 
 
PROTOCOL NUMBER: 
 
BVD-523-ABC  
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
TFL SHELLS 
 
 
 
Author: 
David Manteigas  
Version: 
2.0 
Date: 
01-Jun-2023 


 
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1 Cover and signature pages 
 
Sponsor: 
BioMed Valley Discoveries 
Protocol Number: 
BVD-523-ABC 
Study Title: 
A Two-Part, Phase II, Multi-center Study of the ERK Inhibitor 
Ulixertinib (BVD-523) for Patients with Advanced Malignancies 
Harboring MEK or Atypical BRAF Alterations 
Document Version No 
2.0 
 
We, the undersigned, confirm that we have read, understood and agree to the content of this 
document and hereby authorize its approval. 
Statistician 
Name and Date are not required if electronic signatures are used. Do not resize boxes.  
Name 
Title 
[text box when using 
eSignatures]: 
Date 
Signature 
 
 
 
 
 
 
 
 
 
 


 
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Client Representative 
Name and Date are not required if electronic signatures are used. Do not resize boxes.  
Name 
Title 
[text box when using 
eSignatures]: 
Date 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Senior Scientist
President


 
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2 Document History 
 
Date 
Version 
Modified by 
Brief details of changes made to 
template 
20Dec2021 
1.0 
David Manteigas 
First SAP version 
09Jun2023 
2.0 
David Manteigas 
Updated version to include dry-run 
comments and the required changes 
for the final analysis after the study 
was early terminated. 
 
3 List of Tables, Figures and Listings 
 
Part 
TFL 
Type 
TFL 
Number 
Title 
Population 
Included in 
Final 
Analysis 
 
14.1 
Demographic Data 
 
 
A & B 
Table 
14.1-1.1 
Patient Disposition 
All Patients Set 
Y 
A & B 
Table 
14.1-1.2 
Number of Patients in the Analysis Sets 
All Patients Set 
Y 
A & B 
Table 
14.1-1.3 
Summary of Important Protocol Deviations 
Full Analysis Set 
Y 
A & B 
Table 
14.1-2.1 
Demographics and Baseline Characteristics 
Full Analysis Set 
Y 
A & B 
Table 
14.1-2.2 
Disease History  
Full Analysis Set 
Y 
A & B 
Table 
14.1-2.3 
Summary of Medical History 
Full Analysis Set 
Y 
A & B 
Table 
14.1-2.4 
Summary of Concomitant Diseases 
Full Analysis Set 
Y 
A & B 
Table 
14.1-3.1 
Prior Radiotherapies 
Full Analysis Set 
Y 
A & B 
Table 
14.1-3.2 
Prior Anti-Cancer Therapies  
Full Analysis Set 
Y 
A & B 
Table 
14.1-3.3 
Prior BRAF/MEK inhibitor therapies 
Full Analysis Set 
Y 
A & B 
Table 
14.1-3.4 
Prior Medications 
Full Analysis Set 
Y 
A & B 
Table 
14.1-3.5 
Concomitant Medications 
Full Analysis Set 
Y 
A & B 
Table 
14.1-4.1 
Treatment Exposure 
Full Analysis Set 
Y 
A & B 
Table 
14.1-4.2 
Dosing Interruptions and Adjustments 
Full Analysis Set 
Y 
 
14.2 
Efficacy Data 
 
 
A & B 
Table 
14.2-1.1.1 
Best Overall Response and Overall Response 
Rate 
Full Analysis Set 
Y 
A & B 
Table 
14.2-1.1.2 
Best Overall Response and Overall Response 
Rate 
Per Protocol Set 
 
A & B 
Table 
14.2-1.1.3 
Best Overall Response and Overall Response 
Rate 
Evaluable 
Analysis Set 
 
A & B 
Table 
14.2-1.2.1 
Overall, Target and Non-Target Lesion 
Response 
Full Analysis Set 
Y 
A & B 
Table 
14.2-1.2.2 
Overall, Target and Non-Target Lesion 
Response 
Per Protocol Set 
 
A & B 
Table 
14.2-1.2.3 
Overall, Target and Non-Target Lesion 
Response 
Evaluable 
Analysis Set 
 
A & B 
Table 
14.2-1.3.1 
Incidence of New Lesions 
Full Analysis Set 
Y 
A & B 
Table 
14.2-1.3.2 
Incidence of New Lesions 
Per Protocol Set 
 


 
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A & B 
Table 
14.2-1.3.3 
Incidence of New Lesions 
Evaluable 
Analysis Set 
 
A & B 
Table 
14.2-1.4.1 
Duration of Response (DOR) 
Full Analysis Set 
 
A & B 
Table 
14.2-1.4.2 
Duration of Response (DOR) 
Per Protocol Set 
 
A & B 
Table 
14.2-1.4.3 
Duration of Response (DOR) 
Evaluable 
Analysis Set 
 
A & B 
Table 
14.2-1.5.1 
Progression-free Survival (PFS) 
Full Analysis Set 
Y 
A & B 
Table 
14.2-1.5.2 
Progression-free Survival (PFS) 
Per Protocol Set 
 
A & B 
Table 
14.2-1.5.3 
Progression-free Survival (PFS) 
Evaluable 
Analysis Set 
 
A & B 
Table 
14.2-1.6.1 
Overall Survival (OS) 
Full Analysis Set 
Y 
A & B 
Table 
14.2-1.6.2 
Overall Survival (OS) 
Per Protocol Set 
 
A & B 
Table 
14.2-1.6.3 
Overall Survival (OS) 
Evaluable 
Analysis Set 
 
 
14.3 
Safety Data 
 
 
A & B 
Table 
14.3-1.1 
Overview Summary of Treatment-Emergent 
Adverse Events 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.2 
Summary of Treatment-Emergent Adverse 
Events by System Organ Class and Preferred 
Term 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.3 
Summary of Related Treatment-Emergent 
Adverse Events by System Organ Class and 
Preferred Term  
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.4 
Summary of Serious Treatment-Emergent 
Adverse Events by System Organ Class and 
Preferred Term 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.5 
Summary of Related Serious Treatment-
Emergent Adverse Events by System Organ 
Class and Preferred Term  
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.6 
Summary of Treatment-Emergent Adverse 
Events by Preferred Term 
Safety 
Analysis 
Set 
 
A & B 
Table 
14.3-1.7 
Summary of Related Treatment-emergent 
Adverse Events by Preferred Term 
Safety 
Analysis 
Set 
 
A & B 
Table 
14.3-1.8 
Summary of Serious Treatment-emergent 
Adverse Events by Preferred Term 
Safety 
Analysis 
Set 
 
A & B 
Table 
14.3-1.9 
Summary of Related Serious Treatment-
emergent Adverse Events by Preferred Term 
Safety 
Analysis 
Set 
 
A & B 
Table 
14.3-1.10 
Summary of Treatment-Emergent Adverse 
Events by System Organ Class and Preferred 
Term for Maximum CTCAE grade 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.11 
Summary of Related Treatment-Emergent 
Adverse Events by System Organ Class and 
Preferred Term for Maximum CTCAE grade  
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.12 
Summary of Treatment-emergent Adverse 
Events by System Organ Class and Preferred 
Term Leading to Treatment Discontinuation 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.13 
Summary of Related Treatment-emergent 
Adverse Events by System Organ Class and 
Preferred Term Leading to Treatment 
Discontinuation 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.14 
Summary of Treatment-emergent Adverse 
Events by System Organ Class and Preferred 
Safety 
Analysis 
Set 
Y 


 
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Term Leading to Treatment Discontinuation 
within Cycle 1 
A & B 
Table 
14.3-1.15 
Summary of Related Treatment-emergent 
Adverse Events by System Organ Class and 
Preferred Term Leading to Treatment 
Discontinuation within Cycle 1 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.16 
Summary of Treatment-emergent Adverse 
Events by System Organ Class and Preferred 
Term Leading to Treatment Discontinuation 
following Cycle 1 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.17 
Summary of Related Treatment-emergent 
Adverse Events by System Organ Class and 
Preferred Term Leading to Treatment 
Discontinuation following Cycle 1 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.18 
Summary of Treatment-emergent Adverse 
Events by System Organ Class and Preferred 
Term Leading to Treatment Interruption 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.19 
Summary of Related Treatment-emergent 
Adverse Events by System Organ Class and 
Preferred Term Leading to Treatment 
Interruption 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.20 
Summary of Treatment-emergent Adverse 
Events by System Organ Class and Preferred 
Term Leading to Treatment Interruption 
within Cycle 1 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.21 
Summary of Related Treatment-emergent 
Adverse Events by System Organ Class and 
Preferred Term Leading to Treatment 
Interruption within Cycle 1 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.22 
Summary of Treatment-emergent Adverse 
Events by System Organ Class and Preferred 
Term Leading to Treatment Interruption 
following Cycle 1 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.23 
Summary of Related Treatment-emergent 
Adverse Events by System Organ Class and 
Preferred Term Leading to Treatment 
Interruption following Cycle 1 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.24 
Summary of Treatment-emergent Adverse 
Events by System Organ Class and Preferred 
Term Leading to Dose Reduction 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.25 
Summary of Related Treatment-emergent 
Adverse Events by System Organ Class and 
Preferred Term Leading to Dose Reduction 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.26 
Summary of Treatment-Emergent Adverse 
Events Leading to Dose Reduction within 
Cycle 1 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.27 
Summary of Related Treatment-Emergent 
Adverse Events Leading to Dose Reduction 
within Cycle 1 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.28 
Summary of Treatment-Emergent Adverse 
Events Leading to Dose Reduction following 
Cycle 1 
Safety 
Analysis 
Set 
Y 


 
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A & B 
Table 
14.3-1.29 
Summary of Related Treatment-Emergent 
Adverse Events Leading to Dose Reduction 
following Cycle 1 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.30 
Summary of Treatment-emergent Adverse 
Events by System Organ Class and Preferred 
Term Leading to Death 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.31 
Summary of Related Treatment-emergent 
Adverse Events by System Organ Class and 
Preferred Term Leading to Death  
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-1.32 
Summary of Deaths 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-2.1 
Summary and Change from Baseline in 
Hematology Laboratory Results by Visit 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-2.2.1 
Gradable Hematology Laboratory Results – 
Worst On-treatment Value by Cycle 
Safety 
Analysis 
Set 
 
A & B 
Table 
14.3-2.2.2 
Non-gradable Hematology Laboratory 
Results – Worst On-treatment Value by 
Cycle 
Safety 
Analysis 
Set 
 
A & B 
Table 
14.3-2.3.1 
Shift Table of Gradable Hematology 
Laboratory Results – Baseline vs Worst On-
treatment Value 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-2.3.2 
Shift Table of Non-gradable Hematology 
Laboratory Results – Baseline vs Worst On-
treatment Value 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-2.4 
Summary and Change from Baseline in 
Biochemistry Laboratory Results by Visit 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-2.5.1 
Gradable Biochemistry Laboratory Results – 
Worst On-treatment Value by Cycle 
Safety 
Analysis 
Set 
 
A & B 
Table 
14.3-2.5.2 
Non-gradable Biochemistry Laboratory 
Results – Worst On-treatment Value by 
Cycle 
Safety 
Analysis 
Set 
 
A & B 
Table 
14.3-2.6.1 
Shift Table of Gradable Biochemistry 
Laboratory Results – Baseline vs Worst On-
treatment Value 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-2.6.2 
Shift Table of Non-gradable Biochemistry 
Laboratory Results – Baseline vs Worst On-
treatment Value 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-2.7 
Summary and Change from Baseline in 
Urinalysis Laboratory Results by Visit 
Safety 
Analysis 
Set 
 
A & B 
Table 
14.3-3.1 
Summary and Change from Baseline in Vital 
Signs by Visit 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-3.2 
Shift table of Vital Signs – Baseline vs worst 
on-treatment value 
Safety 
Analysis 
Set 
Y 
A & B 
Table 
14.3-3.3 
Summary of ECG at Baseline 
Safety 
Analysis 
Set 
 
A & B 
Table 
14.3-3.4 
Summary of ECHO/MUGA at Baseline 
Safety 
Analysis 
Set 
 
A & B 
Table 
14.3-3.5 
Summary of Physical Examination at 
Baseline 
Safety 
Analysis 
Set 
 
A & B 
Table 
14.3-3.6 
Summary of ECOG Performance Status by 
Visit 
Safety 
Analysis 
Set 
 
 
14.4 
Other Efficacy Data 
 
 


 
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14.5 
Pharmacokinetic Data 
 
 
A 
Table 
14.5-1.1 
Pharmacokinetic Data 
Full Analysis Set 
Y 
A 
Table 
14.5-1.2 
Pharmacokinetic Data 
Per Protocol Set 
 
A 
Table 
14.5-1.3 
Pharmacokinetic Data 
Evaluable 
Analysis Set 
 
 
14.6 
Blood Pharmacodynamic Data 
 
 
A 
Table 
14.6-1.1 
Blood Pharmacodynamic Data 
Full Analysis Set 
Y 
 
14.2 
Figures 
 
 
A & B 
Figure 
14.2-1.1 
Consort Diagram  
Full Analysis Set 
Y 
A & B 
Figure 
14.2-1.2.1 
Spider plot of Percentage Change from 
Baseline in Sum of Longest Diameter 
Full Analysis Set 
Y 
A & B 
Figure 
14.2-1.2.2 
Spider plot of Percentage Change from 
Baseline in Sum of Longest Diameter 
Per Protocol Set 
 
A & B 
Figure 
14.2-1.2.3 
Spider plot of Percentage Change from 
Baseline in Sum of Longest Diameter 
Evaluable 
Analysis Set 
 
A & B 
Figure 
14.2-1.3.1 
Waterfall plot of Maximum Percentage 
Decrease from Baseline in Sum of Longest 
Diameter 
Full Analysis Set 
Y 
A & B 
Figure 
14.2-1.3.2 
Waterfall plot of Maximum Percentage 
Decrease from Baseline in Sum of Longest 
Diameter 
Per Protocol Set 
 
A & B 
Figure 
14.2-1.3.3 
Waterfall plot of Maximum Percentage 
Decrease from Baseline in Sum of Longest 
Diameter 
Evaluable 
Analysis Set 
 
A & B 
Figure 
14.2-1.4.1 
Swimmer Plot of Response Assessments  
Full Analysis Set 
Y 
A & B 
Figure 
14.2-1.4.2 
Swimmer Plot of Response Assessments  
Per Protocol Set 
 
A & B 
Figure 
14.2-1.4.3 
Swimmer Plot of Response Assessments  
Evaluable 
Analysis Set 
 
A & B 
Figure 
14.2-1.5.1 
Kaplan-Meier Estimate for Duration of 
Response (DOR) 
Full Analysis Set 
 
A & B 
Figure 
14.2-1.5.2 
Kaplan-Meier Estimate for Duration of 
Response (DOR) 
Per Protocol Set 
 
A & B 
Figure 
14.2-1.5.3 
Kaplan-Meier Estimate for Duration of 
Response (DOR) 
Evaluable 
Analysis Set 
 
A & B 
Figure 
14.2-1.6.1 
Kaplan-Meier Estimate for Progression-free 
Survival (PFS) 
Full Analysis Set 
Y 
A & B 
Figure 
14.2-1.6.2 
Kaplan-Meier Estimate for Progression-free 
Survival (PFS) 
Per Protocol Set 
 
A & B 
Figure 
14.2-1.6.3 
Kaplan-Meier Estimate for Progression-free 
Survival (PFS) 
Evaluable 
Analysis Set 
 
A & B 
Figure 
14.2-1.7.1 
Kaplan-Meier Estimate for Overall Survival 
(OS) 
Full Analysis Set 
Y 
A & B 
Figure 
14.2-1.7.2 
Kaplan-Meier Estimate for Overall Survival 
(OS) 
Per Protocol Set 
 
A & B 
Figure 
14.2-1.7.3 
Kaplan-Meier Estimate for Overall Survival 
(OS) 
Evaluable 
Analysis Set 
 
 
16.2 
Patient Data Listings 
 
 
 
16.2.1 
Patient Disposition 
 
 
A & B 
Listing 
16.2.1-1 
Patient Informed Consent 
All Patients Set 
Y 
A & B 
Listing 
16.2.1-2 
Failed Inclusion and Exclusion Criteria 
All Patients Set 
Y 
A & B 
Listing 
16.2.1-3 
Patient Disposition 
All Patients Set 
Y 
Part B 
Listing 
16.2.1-4 
Randomization 
Full Analysis Set 
 


 
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16.2.2 
Analysis Sets   
 
 
A & B 
Listing 
16.2.2-1 
Analysis Sets   
All Patients Set 
 
 
16.2.3 
Protocol Deviations 
 
 
A & B 
Listing 
16.2.3-1 
Protocol Deviations 
Full Analysis Set 
Y 
 
16.2.4 
Demographic Data 
 
 
A & B 
Listing 
16.2.4-1 
Demographics and Baseline Characteristics 
Full Analysis Set 
Y 
A & B 
Listing 
16.2.4-2 
Smoking History 
Full Analysis Set 
 
A & B 
Listing 
16.2.4-3 
Disease History 
Full Analysis Set 
Y 
A & B 
Listing 
16.2.4-4 
Medical History and Concomitant Diseases 
Full Analysis Set 
Y 
A & B 
Listing 
16.2.4-5 
Prior Anti-Cancer Therapies 
Full Analysis Set 
Y 
A & B 
Listing 
16.2.4-6 
Prior BRAF/MEK inhibitor therapies 
Full Analysis Set 
Y 
A & B 
Listing 
16.2.4-7 
Prior Radiotherapies 
Full Analysis Set 
Y 
A & B 
Listing 
16.2.4-8 
Prior and Concomitant Medications  
Full Analysis Set 
Y 
A & B 
Listing 
16.2.4-9 
On Treatment Radiation 
Full Analysis Set 
 
A & B 
Listing 
16.2.4-10 
On Treatment Surgery and Medical 
Procedures 
Full Analysis Set 
 
A & B 
Listing 
16.2.4-11 
On Treatment Blood Transfusions 
Full Analysis Set 
 
A 
Listing 
16.2.4-12 
NGS Data 
Full Analysis Set 
Y 
 
16.2.5 
Compliance and/or Drug Concentration 
Data 
 
 
A & B 
Listing 
16.2.5-1 
Drug Administration 
Full Analysis Set 
Y 
A & B 
Listing 
16.2.5-2 
Dosing Interruptions and Adjustments 
Full Analysis Set 
Y 
A & B 
Listing 
16.2.5-3 
Drug Exposure  
Full Analysis Set 
Y 
A & B 
Listing 
16.2.5-3 
Study Drug Dispensed 
Full Analysis Set 
 
A & B 
Listing 
16.2.5-4 
Study Drug Returned 
Full Analysis Set 
 
 
16.2.6 
Individual Efficacy Response data 
 
 
A & B 
Listing 
16.2.6-1 
Target Lesions 
Full Analysis Set 
Y 
A & B 
Listing 
16.2.6-2 
Non-Target Lesions 
Full Analysis Set 
Y 
A & B 
Listing 
16.2.6-3 
New Lesions 
Full Analysis Set 
Y 
A & B 
Listing 
16.2.6-4 
Overall Response 
Full Analysis Set 
Y 
A & B 
Listing 
16.2.6-5 
Duration of Response (DOR) 
Full Analysis Set 
 
A & B 
Listing 
16.2.6-6 
Progression-Free Survival (PFS) 
Full Analysis Set 
Y 
A & B 
Listing 
16.2.6-7 
Survival Status 
Full Analysis Set 
Y 
 
16.2.7 
Adverse Events 
Full Analysis Set 
 
A & B 
Listing 
16.2.7-1 
Adverse Events 
All Patients Set 
Y 
A & B 
Listing 
16.2.7-2 
Treatment Emergent Adverse Events 
Safety 
Analysis 
Set 
Y 
A & B 
Listing 
16.2.7-3 
Serious Adverse Events 
Safety 
Analysis 
Set 
Y 
A & B 
Listing 
16.2.7-4 
Deaths 
Safety 
Analysis 
Set 
Y 
 
16.2.8 
Laboratory Data 
 
 
A & B 
Listing 
16.2.8-1 
Hematology  
Safety 
Analysis 
Set 
Y 
A & B 
Listing 
16.2.8-2 
Biochemistry 
Safety 
Analysis 
Set 
Y 
A & B 
Listing 
16.2.8-3 
Urinalysis 
Safety 
Analysis 
Set 
Y 
A & B 
Listing 
16.2.8-4 
Pregnancy  
Safety 
Analysis 
Set 
 
 
16.2.9 
Other Safety Data 
 
 


 
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A & B 
Listing 
16.2.9-1 
Vital Signs 
Safety 
Analysis 
Set 
Y 
A & B 
Listing 
16.2.9-2 
Electrocardiogram 
Safety 
Analysis 
Set 
Y 
A & B 
Listing 
16.2.9-3 
ECHO/MUGA 
Safety 
Analysis 
Set 
Y 
A & B 
Listing 
16.2.9-4 
Physical Examination 
Safety 
Analysis 
Set 
Y 
A & B 
Listing 
16.2.9-5 
Ophthalmology exam 
Safety 
Analysis 
Set 
Y 
A & B 
Listing 
16.2.9-6 
Meals 
Safety 
Analysis 
Set 
 
A & B 
Listing 
16.2.9-7 
ECOG Performance Status 
Safety 
Analysis 
Set 
Y 
A 
16.2.10 
Pharmacodynamic Data 
 
 
A 
Listing 
16.2.10-1 
Blood Pharmacodynamic Data 
Full Analysis Set 
Y 
A 
16.2.11 
Pharmacokinetic Data 
 
 
A 
Listing 
16.2.11-1 
Pharmacokinetic Data 
Full Analysis Set 
Y 
Y = Output that will be included in the final analysis 
  
 
 


 
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4 General programming notes 
 
For Part A, all tables will be reported by molecular alteration group. For Part B, all tables will be 
reported by selected tumor histology group and treatment group. Tables for All Patients Set will 
include a column for Screen Failures. 
An ‘Overall’ column will be included in all tables. 
All tables marked as Part A & Part B in the TFLs list will be replicated, just changing the columns 
and page headers, as indicated in the table below. Shells will be created using Part A headers. 
 
Table 
Column headers 
Phase in Page 
Header 
Part A 
Group 1 
Group 2 
Group 3 
Group 4 
Group 5 
Group 6 
Overall 
Part A 
 
Part B 
Group 1 
Group 2 
Comparator 
Overall 
Part B 
 
 
The full-page header to be included for each delivery is indicated in the table below: 
Delivery 
Type 
Page Header 
Dry run 
Dry run 
Dry-run – Part A/B 
Final analysis 
Draft 
Draft – Part A/B 
Final 
Final – Part A/B 
 
For the listings, all cases where 'Other’ is present, please present the respective ‘Other’ 
specification. 
All Listings will be sorted by Group and patient ID. A programming note will be added to each 
Listing when another variable is needed to make the sorting meaningful (e.g., assessment date).


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y   
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-1.1 – Patient Disposition 
All Patients Set 
 
 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Screen 
Failures 
N=XX 
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
 
Patients enrolled [a] 
XX  
XX  
XX  
XX  
XX  
XX  
XX  
XX  
 
 
 
 
 
 
 
 
 
Patients completed screening [b] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Discontinued from screening [b] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Primary reason for discontinuation [c] 
 
 
 
 
 
 
 
 
     Adverse Event  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Death 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Pregnancy 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Screen Failure 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Study Terminated by Sponsor 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Lost to Follow-up 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Technical Problems 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Physician Decision 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Withdrawal by Patient 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
Patients rescreened [b] 
 
 
 
 
 
 
 
 
  Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
Patients eligible for inclusion in the study [b] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
Patients treated with study drug [b] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
[a] Patients who signed the informed consent.  
[b] Percentages are calculated from the number of patients enrolled. 
[c] Percentages are calculated from the number of patients who discontinued from screening. 
[d] Percentages are calculated from the number of patients who were treated with study drug. 
[e] Percentages are calculated from the number of patients who discontinued from treatment. 
[f] Percentages are calculated from the number of patients who discontinued from study. 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 


 
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BioMed Valley Discoveries                                                                                                Page 2 of Y   
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
 
Table 14.1-1.1 – Patient Disposition 
All Patients Set 
 
 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Screen 
Failures 
N=XX 
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
 
Patients completed treatment [d] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Discontinued from treatment [d] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Primary reason for discontinuation [e] 
 
 
 
 
 
 
 
 
     Death 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Progressive Disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Adverse Event 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Pregnancy 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Withdrawal by Patient     
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Protocol Violation 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Lost to Follow-up 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Physician Decision 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Study Terminated by Sponsor 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
[a] Patients who signed the informed consent.  
[b] Percentages are calculated from the number of patients enrolled. 
[c] Percentages are calculated from the number of patients who discontinued from screening. 
[d] Percentages are calculated from the number of patients who were treated with study drug. 
[e] Percentages are calculated from the number of patients who discontinued from treatment. 
[f] Percentages are calculated from the number of patients who discontinued from study. 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 14 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 3 of Y   
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-1.1 – Patient Disposition 
All Patients Set 
 
 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Screen 
Failures 
N=XX 
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
 
      
 
 
 
 
 
 
 
 
Discontinued from study [b] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Primary reason for discontinuation [f] 
 
 
 
 
 
 
 
 
     Completed study 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Adverse Event 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Progressive Disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Death 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Withdrawal by Patient 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Physician Decision 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Lost to Follow-up 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Pregnancy 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Protocol Violation 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Sponsor Request 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Protocol-Specified Withdrawal Criterion Met 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
     Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
[a] Patients who signed the informed consent.  
[b] Percentages are calculated from the number of patients enrolled. 
[c] Percentages are calculated from the number of patients who discontinued from screening. 
[d] Percentages are calculated from the number of patients who were treated with study drug. 
[e] Percentages are calculated from the number of patients who discontinued from treatment. 
[f] Percentages are calculated from the number of patients who discontinued from study. 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Display all possible reasons, either reported for at least one subject or not. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 15 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y   
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-1.2 – Number of Patients in the Analysis Sets 
All Patients Set 
 
 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Screen 
Failures 
N=XX 
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
 
All Patients Set [a] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Full Analysis Set [b] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Safety Analysis Set [c]  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Per Protocol Analysis Set [d] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Evaluable Analysis Set [e] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
[a] Patients who were enrolled regardless of whether they received the study drug or not. 
[b] Patients who received at least 1 dose of the study drug. 
[c] Patients who received at least 1 dose of the study drug. 
[d] All patients from FAS who completed the study without any important protocol deviations. 
[e] All patients from FAS who had the first efficacy evaluation on Study Day 29±3 and completed the study without any important protocol 
deviations. 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 16 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y   
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-1.3 – Summary of Important Protocol Deviations 
Full Analysis Set 
 
 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
Number of patients with at least  
one important protocol deviation 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Deviation category 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Summary term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Summary term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Deviation category 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Summary term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Summary term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Note: A patient with multiple occurences of a protocol deviation is counted only once in this deviation category/summary term. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Categories / Summary terms to match the PDCF.  
 
Present only important protocol deviations with at least one occurrence (where classification=Important). 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 17 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y   
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-2.1 – Demographics and Baseline Characteristics 
Full Analysis Set 
 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
Age (Years) 
 
 
 
 
 
 
 
 n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 Mean (SD) 
XX.XX (XX.XX) XX.XX (XX.XX) XX.XX (XX.XXX) XX.XX (XX.XX) XX.XX (XX.XX) XX.XX (XX.XX) XX.XX (XX.XX) 
 Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 Min; Max 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
 
 
 
 
 
 
 
 
Age category (Years) n (%) 
 
 
 
 
 
 
 
 18 - 64 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 65 - 84 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 >=85 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Gender – n (%) 
 
 
 
 
 
 
 
 Female 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Childbearing potential n (%) [a]  
 
 
 
 
 
 
      Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
      No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 Male 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Reproductive potential n (%) [a]  
 
 
 
 
 
 
      Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
      No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
[a] Percentages are calculated from the number of patients within gender. 
[b] Last non-missing value prior to first dose of study treatment. 
[c] Body Mass Index (BMI)=Weight (kg)/ Height(m)^2. 
[d] 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; 2=Ambulatory and capable of all self-care 
but unable to carry out any work activities.       
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.doc) 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 18 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 2 of Y     
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-2.1 - Demographics and Baseline Characteristics 
Full Analysis Set 
 
  
  
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
Race – n (%) 
 
 
 
 
 
 
 
  American Indian or  
  Alaska Native 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Asian  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Black or African American 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Native Hawaiian or Other    
  Pacific Islander 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  White 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Ethnicity – n (%) 
 
 
 
 
 
 
 
  Hispanic or Latino 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Not Hispanic or Latino 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Unknown 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Weight (kg) [b] 
 
 
 
 
 
 
 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
[a] Percentages are calculated from the number of patients within gender. 
[b] Last non-missing value prior to first dose of study treatment. 
[c] Body Mass Index (BMI)=Weight (kg)/ Height(m)^2. 
[d] 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; 2=Ambulatory and capable of all self-care 
but unable to carry out any work activities.       
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.doc) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 19 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 3 of Y     
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-2.1 - Demographics and Baseline Characteristics 
Full Analysis Set 
 
  
  
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
Height (cm) [b] 
 
 
 
 
 
 
 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
BMI at Baseline(kg/m^2) [c] 
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
ECOG performance at Baseline – n 
(%) [d] 
 
 
 
 
 
 
 
  0  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  2  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Smoking History – n (%) 
 
 
 
 
 
 
 
  Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Current 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Former 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
[a] Percentages are calculated from the number of patients within gender. 
[b] Last non-missing value prior to first dose of study treatment. 
[c] Body Mass Index (BMI)=Weight (kg)/ Height(m)^2. 
[d] 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; 2=Ambulatory and capable of all self-care 
but unable to carry out any work activities.       
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.doc) 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 20 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 4 of Y   
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
 
Table 14.1-2.1 - Demographics and Baseline Characteristics 
Full Analysis Set 
 
  
  
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
Gene 
 
 
 
 
 
 
 
   BRAF  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   MEK1/MAP2K1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   MEK2/MAP2K2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Codon 
 
 
 
 
 
 
 
   G469 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   … 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Amino acid change 
 
 
 
 
 
 
 
   Alanine A 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Arginine R 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   … 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Other: xxxx 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[a] Percentages are calculated from the number of patients within gender. 
[b] Last non-missing value prior to first dose of study treatment. 
[c] Body Mass Index (BMI)=Weight (kg)/ Height(m)^2. 
[d] 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; 2=Ambulatory and capable of all self-care 
but unable to carry out any work activities.       
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.doc) 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 21 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 5 of Y   
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
 
Table 14.1-2.1 - Demographics and Baseline Characteristics 
Full Analysis Set 
 
  
  
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
NGS Vendor 
 
 
 
 
 
 
 
   STRATA 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   FOUNDATION MEDICINE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   GUARDANT 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   CARIS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   TEMPUS 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   OTHER 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
[a] Last non-missing value prior to first dose of study treatment. 
[b] Body Mass Index (BMI)=Weight (kg)/ Height(m)^2. 
[c] 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; 2=Ambulatory and capable of all self-care 
but unable to carry out any work activities.       
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.doc) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 22 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y   
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-2.2 – Disease History 
Full Analysis Set 
 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
Cancer Diagnosis– n (%) 
 
 
 
 
 
 
 
  Adenoid Cystic 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Anal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Appendiceal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Basal Cell Carcinoma 
  of the Skin 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
 
 
 
 
 
 
 
  Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Time since initial diagnosis 
(months) [a] 
 
 
 
 
 
 
 
  n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
  Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX)
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
Disease stage at initial  
diagnosis – n (%) 
 
 
 
 
 
 
 
  1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[a] Calculated as (date of first dose of study treatment - date of diagnosis) / 30.4375.  
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 23 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 2 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-2.2 – Disease History 
Full Analysis Set 
 
 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
Disease stage at enrollment – n (%) 
 
 
 
 
 
 
 
   1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Method of diagnosis – n (%) 
 
 
 
 
 
 
 
   Cytological 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Histological 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Prior Cancer Therapies/Regimens – n (%) 
 
 
 
 
 
 
 
   Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Prior BRAF/MEK Inhibitor Therapies – n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior Radiation Therapies – n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[a] Calculated as (date of first dose of study treatment - date of diagnosis) / 30.4375.  
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 24 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-2.3 – Summary of Medical History 
Full Analysis Set 
 
System Organ Class 
  Preferred Term 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
Any relevant medical history 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
System organ class 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
System organ class 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Note: MedDRA <vx.x>. 
If there is more than one medical history within a system organ class (SOC), the patient is counted only once under that SOC. If there 
is more than one medical history within a SOC and preferred term (PT), the patient is counted only once in that SOC and PT. 
Primary SOCs are presented by descending order of frequency for the overall group, PTs are sorted by descending order of frequency for 
the overall group within primary SOC. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 25 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-2.4 – Summary of Concomitant Diseases 
Full Analysis Set 
 
System Organ Class 
  Preferred Term 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
Any relevant concomitant disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
System organ class 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
System organ class 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Note: MedDRA <vx.x>. 
If there is more than one concomitant disease within a system organ class (SOC), the patient is counted only once under that SOC. If 
there is more than one concomitant disease within a SOC and preferred term (PT), the patient is counted only once in that SOC and PT. 
Primary SOCs are presented by descending order of frequency for the overall group, PTs are sorted by descending order of frequency for 
the overall group within primary SOC. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 26 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-3.1 – Prior Radiotherapies 
Full Analysis Set 
 
 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
Received at least one prior  
radiotherapy - n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Total number of prior radiotherapies - n (%) 
 
 
 
 
 
 
 
1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Total number of prior radiotherapies by group 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
Site of prior radiotherapy - n (%) [a] [b] 
 
 
 
 
 
 
 
    Abdominal Cavity 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Adrenal Gland 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    ………… 
 
 
 
 
 
 
 
    Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Most recent prior radiotherapy before study 
treatment start 
 
 
 
 
 
 
 
  Site of prior radiotherapy - n (%) 
 
 
 
 
 
 
 
    Abdominal Cavity 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    ………… 
 
 
 
 
 
 
 
    Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
  Duration of therapy (months) [c] 
 
 
 
 
 
 
 
    n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    Mean (SD) 
XX.X 
(XX.XX) 
XX.X 
(XX.XX) 
XX.X 
(XX.XX) 
XX.X 
(XX.XX) 
XX.X 
(XX.XX) 
XX.X 
(XX.XX) 
XX.X 
(XX.XX) 
    Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
    Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[a] Patients can have more than 1 site of prior radiotherapy if they had multiple prior radiotherapies.  
[b] Percentages calculated from the total number of radiotherapies 
[c] Calculated as [(end date of therapy - start date of therapy)+1] / 30.4375. 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 27 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                       Filename: (Specify file name.rtf) 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-3.2 – Prior Anti-Cancer Therapies 
Full Analysis Set 
 
 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
Received at least one prior anti-cancer  
Therapy - n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Lines of prior anti-cancer therapies - n (%) 
 
 
 
 
 
 
 
  1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  …  
 
 
 
 
 
 
 
  Mean (SD) 
XX.X 
(XX.XX) 
XX.X 
(XX.XX) 
XX.X 
(XX.XX) 
XX.X 
(XX.XX) 
XX.X 
(XX.XX) 
XX.X 
(XX.XX) 
XX.X 
(XX.XX) 
  Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
  Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
Most recent therapy before study treatment start 
 
 
 
 
 
 
 
  Regimen name - n (%) 
 
 
 
 
 
 
 
    xxxxxxxx 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    xxxxxxxx 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    xxxxxxxx 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Note: Regimen name sorted by decreasing frequency in the overall column.  
[a] Calculated as [(end date of therapy - start date of therapy)+1] / 30.4375.  
[b] Calculated as [(date of first study treatment - date of BOR)+1] / 30.4375.  
[c] Calculated as [(date of first study treatment - date of Relapse/Progression)+1] / 30.4375. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                      Filename: (Specify file name.rtf) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 28 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 2 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-3.2 – Prior Anti-Cancer Therapies 
Full Analysis Set 
 
 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
  Best Response - n (%) 
 
 
 
 
 
 
 
    Complete Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Partial Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Stable Disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Progressive Disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Not Evaluable 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Not Done 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
  Duration of therapy (months) [a] 
 
 
 
 
 
 
 
    n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) XX.X (XX.XX) 
    Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
    Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
  Time since Best Overall Response 
   (months) [b] 
 
 
 
 
 
 
 
    n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) XX.X (XX.XX) 
    Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
    Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
[a] Calculated as [(end date of therapy - start date of therapy)+1] / 30.4375.  
[b] Calculated as [(date of first study treatment - date of BOR)+1] / 30.4375.  
[c] Calculated as [(date of first study treatment - date of Relapse/Progression)+1] / 30.4375. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                         Filename: (Specify file name.rtf) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 29 of 144 
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Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 3 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-3.2 – Prior Anti-Cancer Therapies 
Full Analysis Set 
 
 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
   Time since Relapse/Progression 
   (months) [c] 
 
 
 
 
 
 
 
    n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) XX.X (XX.XX) 
    Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
    Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
   Reason for discontinuation – n (%) 
 
 
 
 
 
 
 
    Intolerance 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Lack of Efficacy (incl. PD) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Completed Therapy 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
[a] Calculated as [(end date of therapy - start date of therapy)+1] / 30.4375.  
[b] Calculated as [(date of first study treatment - date of BOR)+1] / 30.4375.  
[c] Calculated as [(date of first study treatment - date of Relapse/Progression)+1] / 30.4375. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                         Filename: (Specify file name.rtf) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 30 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-3.3 – Prior BRAF/MEK inhibitor therapies 
Full Analysis Set 
 
 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
Received at least one prior BRAF/MEK inhibitor 
therapy - n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Prior BRAF/MEK inhibitor therapies - n (%) 
 
 
 
 
 
 
 
  Vemurafenib 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Dabrafenib 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Encorafenib 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Trametinib 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  …  
 
 
 
 
 
 
 
  Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Most recent therapy before study treatment start 
 
 
 
 
 
 
 
  BRAF/MEK inhibitor therapies - n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Vemurafenib 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Dabrafenib 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Encorafenib 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  …  
 
 
 
 
 
 
 
  Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Note: Based on tumor alteration groups, only patients from Groups 5 and 6 are expected to have prior BRAF/MEK inhibitor therapies.  
[a] Calculated as [(end date of therapy - start date of therapy)+1] / 30.4375.  
[b] As collected from the CRF page: Prior BRAF/MEK inhibitor therapies. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 31 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 2 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-3.3 – Prior BRAF/MEK inhibitor therapies 
Full Analysis Set 
 
 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
  Best Response - n (%) 
 
 
 
 
 
 
 
    Complete Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Partial Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Stable Disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Progressive Disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Not Evaluable 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Not Done 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
  Duration of therapy (months) [a] 
 
 
 
 
 
 
 
    n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) XX.X (XX.XX) 
    Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
    Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
  Duration of Response (months) [b] 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
    Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) XX.X (XX.XX) 
    Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
    Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
  Reason for discontinuation – n (%) 
 
 
 
 
 
 
 
    Intolerance 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Lack of Efficacy (incl. PD) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Completed Therapy 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Note: Based on tumor alteration groups, only patients from Groups 5 and 6 are expected to have prior BRAF/MEK inhibitor therapies.  
[a] Calculated as [(end date of therapy - start date of therapy)+1] / 30.4375.  
[b] As collected from the CRF page: Prior BRAF/MEK inhibitor therapies. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                        Filename: (Specify file name.rtf) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 32 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-3.4 – Prior Medications 
Full Analysis Set 
 
ATC Class 
  Preferred Term 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Any Prior Medications 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
ATC class 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
ATC class 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: WHOHD-B3 <vx.x>. ATC=Anatomical Therapeutic Chemical. 
If there is more than one medication within an ATC class, the patient is counted only once under that ATC class. If there is more than one 
medication within an ATC class and preferred term (PT), the patient is counted only once in that ATC class and PT.  
ATC classes are presented by descending order of frequency for the overall group, PTs are sorted by descending order of frequency for the 
overall group within ATC class. 
Prior medication is defined as any medications whose end date is before the first study treatment date. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 33 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
Table 14.1-3.5 – Concomitant Medications 
Full Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.1-3.4 
 
Present concomitant medications. 
 
Replace footnote ‘Prior medication is defined as…’  with the following footnote: 
‘Concomitant medication is defined as any medication ongoing at first day of study drug or started after first day of study drug up to the end of the on-
treatment period.’ 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 34 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-4.1 – Treatment exposure  
Full Analysis Set 
 
 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
Number of cycles received 
[a] - n (%) 
 
 
 
 
 
 
 
   1  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   … 
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
   Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Min; Max 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
 
 
 
 
 
 
 
 
Duration of exposure to  
ulixertinib (months) [b] – n 
(%) 
 
 
 
 
 
 
 
   < 1 month 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   1-2 months 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   2-3 months 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   … 
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
   Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Min; Max 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[a] Number of cycles received = Number of cycles where the patient received at least one dose. 
[b] Duration of exposure (months) = [(Date of last known treatment dosing with ulixertinib – date of initial dosing with ulixertinib) + 1] 
/ 30.4375. 
[c] Actual cumulative dose received (mg) = Sum of [(number of capsules dispensed – number of capsules returned) x 150. 
[d] Relative dose intensity = 100 x Actual dose intensity / Planned dose intensity. Actual dose intensity (mg/day) is defined as Actual 
cumulative dose received (mg) / Duration of exposure (days). Planned dose intensity (mg/day) is defined as Planned cumulative dose (mg) / 
Duration of exposure (days). 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 35 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 2 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-4.1 – Treatment exposure  
Full Analysis Set 
 
 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
Actual cumulative dose on  
ulixertinib (mg) [c] 
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
   Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Min; Max 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
 
 
 
 
 
 
 
 
Relative dose intensity [d] 
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
   Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Min; Max 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[a] Number of cycles received = Number of cycles where the patient received at least one dose. 
[b] Duration of exposure (days) = (Date of last known treatment dosing with ulixertinib – date of initial dosing with ULIXERTINIB) + 1. 
[c] Actual cumulative dose received (mg) = Sum of [(number of capsules dispensed – number of capsules returned) x 150. 
[d] Relative dose intensity = 100 x Actual dose intensity / Planned dose intensity. Actual dose intensity (mg/day) is defined as Actual cumulative 
dose received (mg) / Duration of exposure (days). Planned dose intensity (mg/day) is defined as Planned cumulative dose (mg) / Duration of exposure 
(days). 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                           Filename: (Specify file name.rtf) 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 36 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.1-4.2 – Dosing Interruptions and Adjustments 
Full Analysis Set 
 
 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
At least one dose change – n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Reason dose changed – n (%) [a] 
 
 
 
 
 
 
 
   Adverse event 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Parental/Guardian decision 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Consent withdrawal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   … 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Other 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dose changed to – n (%) [b] 
 
 
 
 
 
 
 
  150mg BID 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  300mg BID 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  450mg BID 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  600mg BID 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
At least one dose interruption – n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Reason dose interrupted [a] 
 
 
 
 
 
 
 
  Adverse Event  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Dispensing Error 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Investigator Decision 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Consent Withdrawal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Patient Decision 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
[a] A patient can be counted under several reasons if they had multiple different dose changes/interruptions. 
[b] A patient can be counted under more than one dose level if they had multiple different dose changes. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                       Filename: (Specify file name.rtf) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                  Page 1 of Y  
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.2-1.1.1 – Best Overall Response and Overall Response Rate  
Full Analysis Set 
 
 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
Best overall response – n (%) [a] 
 
 
 
 
 
 
 
  Complete response (CR) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Partial response (PR) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Stable disease (SD) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Progressive disease (PD) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Not evaluable (NE) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Overall response rate (CR+PR) – n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
95 % CI for Overall response rate 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) (XX.X, XX.X) 
 
 
 
 
 
 
 
 
Disease Control Rate (CR+PR+SD) – n 
(%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
95 % CI for Overall response rate 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) (XX.X, XX.X) 
 
 
 
 
 
 
 
 
Non responders (SD+PD+NE) – n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: CI=Confidence Interval. 
95% CI is estimated using the Clopper-Pearson method. 
[a] Confirmed Best overall response as per RECIST 1.1 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                         Filename: (Specify file name.rtf) 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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Version 5.0 25Jun2020 
 
 
 
 
Table 14.2-1.1.2 – Best Overall Response and Overall Response Rate 
Per Protocol Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.2-1.1.1 
 
Present data on Per Protocol Set. 
 
For Part B only 
 
Table 14.2-1.1.3 – Best Overall Response and Overall Response Rate 
Evaluable Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.2-1.1.1 
 
Present data on Evaluable Analysis Set. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 39 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                  Page 1 of Y  
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.2-1.2.1 – Overall, Target and Non-Target Lesion Response  
Full Analysis Set 
 
 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
C1D28 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Target Lesion Response – n (%) 
 
 
 
 
 
 
 
  Complete response (CR) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Partial response (PR) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Stable disease (SD) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Progressive disease (PD) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Not evaluable (NE) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Non-Target Lesion Response – n (%) 
 
 
 
 
 
 
 
  Complete response (CR) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Non-Complete Response/Non   
Progressive Disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Progressive disease (PD) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Not Applicable 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Overall Response – n (%) 
 
 
 
 
 
 
 
  Complete response (CR) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Partial Response (PR) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Stable Disease (SD) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Progressive disease (PD) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Not Evaluable (NE) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Programming Note: Repeat for all 
available assessments 
 
 
 
 
 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                         Filename: (Specify file name.rtf) 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 40 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
Table 14.2-1.2.2 – Overall, Target and Non-Target Lesion Response 
Per Protocol Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.2-1.2.1 
 
Present data on Per Protocol Set. 
 
For Part B only 
 
Table 14.2-1.2.3 – Overall, Target and Non-Target Lesion Response 
Evaluable Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.2-1.2.1 
 
Present data on Evaluable Analysis Set. 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 41 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                  Page 1 of Y  
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.2-1.3.1 – Incidence of New Lesions  
Full Analysis Set 
 
 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
C1D28 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
New Lesions – n (%) 
 
 
 
 
 
 
 
  Yes  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Number of New Lesions – n (%) 
 
 
 
 
 
 
 
1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
… 
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
XX.XX (XX.XX) 
   Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
   Min; Max 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programming Note: Repeat for 
all available assessments 
 
 
 
 
 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                         Filename: (Specify file name.rtf) 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 42 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
Table 14.2-1.3.2 – Incidence of New Lesions 
Per Protocol Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.2-1.3.1 
 
Present data on Per Protocol Set. 
 
For Part B only 
 
Table 14.2-1.3.3 – Incidence of New Lesions 
Evaluable Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.2-1.3.1 
 
Present data on Evaluable Analysis Set. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 43 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.2-1.4.1 – Duration of Response  
Full Analysis Set 
 
 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
Patients with response (CR+PR) – n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Patients with events – n (%) [a] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Patients censored – n (%) [a] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Duration of response (months) [b] 
 
 
 
 
 
 
 
  Median (95% CI)  
XX 
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
  Min, Max 
XX, XX* 
XX, XX  
XX, XX  
XX, XX*  
XX, XX  
XX, XX*  
XX, XX  
 
 
 
 
 
 
 
 
KM probability estimates for duration 
of response (95% CI) [c] 
 
 
 
 
 
 
 
  3 Months 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
  6 Months 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
  9 Months 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
 12 Months 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
 18 Months 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
 
 
 
 
 
 
 
 
Note: CI=Confidence Interval, CR=Complete Response, PR=Partial Response. 
Duration of response is the period from the date of initial PR or CR until the date of first radiographically documented progressive disease or 
death from any cause.  
[a] Percentage calculated on patients with response. Events are death or disease progression.  
[b] Product-limit (Kaplan-Meier) estimates. 95% CI for median calculated using the Brookmeyer and Crowley method. 
[c] Based upon Kaplan-Meier (KM) estimates and 95% CI use the log-log transformation. 
* Censored observation at maximum value. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                         Filename: (Specify file name.rtf) 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 44 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
Table 14.2-1.4.2 – Duration of Response  
Per Protocol Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.2-1.4.1 
 
Present data on Per Protocol Set. 
 
For Part B only 
 
Table 14.2-1.4.3 – Duration of Response  
Evaluable Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.2-1.4.1 
 
Present data on Evaluable Analysis Set. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 45 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.2-1.5.1 – Progression-Free Survival (PFS) 
Full Analysis Set 
 
 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
Patients with events – n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Patients censored – n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
PFS (months) [a] 
 
 
 
 
 
 
 
  Median (95% CI)  
XX (X.X, 
X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
  Min, Max 
XX, XX* 
XX, XX  
XX, XX  
XX, XX*  
XX, XX  
XX, XX*  
XX, XX  
 
 
 
 
 
 
 
 
KM probability estimates for PFS (95% CI) 
[b] 
 
 
 
 
 
 
 
  3 Months 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
  6 Months 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
  9 Months 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
 12 Months 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
 18 Months 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: CI=Confidence Interval. 
Progression-Free Survival (PFS) is the time from the first ulixertinibdose until the first radiographically documented progression of disease or 
death from any cause, whichever occurs first. 
[a] Product-limit (Kaplan-Meier) estimates. 95% CI for median calculated using the Brookmeyer and Crowley method. 
[b] Based upon Kaplan-Meier (KM) estimates and 95% CI use the log-log transformation. 
* Censored observation at maximum value. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                         Filename: (Specify file name.rtf) 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 46 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
Table 14.2-1.5.2 – Progression-Free Survival (PFS) 
Per Protocol Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.2-1.5.1 
 
Present data on Per Protocol Set. 
 
For Part B only 
Table 14.2-1.5.3 – Progression-Free Survival (PFS) 
Evaluable Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.2-1.5.1 
 
Present data on Evaluable Analysis Set. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 47 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X  
Data extraction date: DDMMMYYYY 
Table 14.2-1.6.1 – Overall Survival (OS) 
Full Analysis Set 
 
 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
Patients with events – n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Patients censored – n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
OS (months) [a] 
 
 
 
 
 
 
 
  Median (95% CI)  
XX (X.X, 
X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
  Min, Max 
XX, XX* 
XX, XX  
XX, XX  
XX, XX*  
XX, XX  
XX, XX*  
XX, XX  
 
 
 
 
 
 
 
 
KM probability estimates for PFS (95% CI) 
[b] 
 
 
 
 
 
 
 
  3 Months 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
  6 Months 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
  9 Months 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
 12 Months 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
 18 Months 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
XX  
(X.X, X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: CI=Confidence Interval. 
Overall Survival (OS) is the time from the first ulixertinib dose until death from any cause. 
[a] Product-limit (Kaplan-Meier) estimates. 95% CI for median calculated using the Brookmeyer and Crowley method. 
[b] Based upon Kaplan-Meier (KM) estimates and 95% CI use the log-log transformation. 
* Censored observation at maximum value. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                         Filename: (Specify file name.rtf) 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 48 of 144 
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Table 14.2-1.6.2 – Overall Survival (OS) 
Per Protocol Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.2-1.6.1 
 
Present data on Per Protocol Set. 
 
For Part B only 
Table 14.2-1.6.3 – Overall Survival (OS) 
Evaluable Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.2-1.6.1 
 
Present data on Evaluable Analysis Set. 
 
 


 
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Statistical Analysis Plan:  
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-1.1 – Overview Summary of Treatment-Emergent Adverse Events 
Safety Analysis Set 
 
 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
Number of patients with: 
 
 
 
 
 
 
 
Any TEAE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any Related TEAE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any SAE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any Related SAE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any TEAE leading to treatment discontinuation 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any Related TEAE leading to treatment discontinuation 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any TEAE leading to treatment discontinuation within 1 
cycle 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any Related TEAE leading to treatment discontinuation 
within 1 cycle 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any TEAE leading to treatment discontinuation 
following 1 cycle 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any Related TEAE leading to treatment discontinuation 
following 1 cycle 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any TEAE leading to treatment interruption 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any Related TEAE leading to treatment interruption 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any TEAE leading to treatment interruption within 1 
cycle 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any Related TEAE leading to treatment interruption 
within 1 cycle 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any TEAE leading to treatment interruption following 1 
cycle 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any Related TEAE leading to treatment interruption 
following 1 cycle 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Note: SAE=Serious Adverse Events, TEAE=Treatment-Emergent Adverse Events 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                         Filename: (Specify file name.rtf) 
 
 


 
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Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-1.1 – Overview Summary of Treatment-Emergent Adverse Events 
Safety Analysis Set 
 
 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
Number of patients with: 
 
 
 
 
 
 
 
Any TEAE leading to dose reduction  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any related TEAE leading to dose reduction  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any TEAE leading to dose reduction within 
Cycle 1  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any Related TEAE leading to dose reduction 
within Cycle 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any TEAE leading to dose reduction following 
Cycle 1  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any Related TEAE leading to dose reduction 
following Cycle 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any TEAE leading to death 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any Related TEAE leading to death 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any TEAE with Grade >= 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Any Related TEAE with Grade >= 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Note: SAE=Serious Adverse Events, TEAE=Treatment-Emergent Adverse Events 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                         Filename: (Specify file name.rtf) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
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Template Author: Andra Rusu 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-1.2 – Summary of Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Analysis Set 
 
 
System Organ Class 
  Preferred Term 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
Any TEAE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
System organ class 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
System organ class 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: MedDRA <vx.x>. TEAE=Treatment-Emergent Adverse Events. 
If there is more than one TEAE within a system organ class (SOC), the patient is counted only once under that SOC. If there is more than one TEAE 
within a SOC and preferred term (PT), the patient is counted only once in that SOC and PT. 
Primary SOCs are presented by descending order of frequency for the overall group, PTs are sorted by descending order of frequency for the 
overall group within each SOC. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                        Filename: (Specify file name.rtf) 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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Version 5.0 25Jun2020 
 
 
 
 
Table 14.3-1.3 – Summary of Related Treatment-emergent Adverse Events by System Organ Class and Preferred Term 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.2 
 
Present Related TEAE: TEAEs with causality=Related, Possibly Related or missing. 
 
Add footnote: 
“Related TEAE: TEAEs with causality=Related, Possibly Related or missing.” 
 
Table 14.3-1.4 – Summary of Serious Treatment-emergent Adverse Events by System Organ Class and Preferred Term 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.2 
 
Present Serious TEAE: TEAEs with SAE =” Yes”. 
 
Add footnote: 
“Serious TEAE: TEAEs with SAE =” Yes”.” 
 
Table 14.3-1.5 – Summary of Related Serious Treatment-emergent Adverse Events by System Organ Class and Preferred Term 
 
 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.2 
 
Present Related Serious TEAE: SAEs with causality=Related, Possibly Related or missing. 
 
Add footnote: 
“SAEs with causality=Related, Possibly Related or missing.” 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
 
Table 14.3-1.6 – Summary of Treatment-Emergent Adverse Events by Preferred Term 
Safety Analysis Set 
 
System Organ Class 
  Preferred Term 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
Any TEAE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
  Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: MedDRA <vx.x>. TEAE=Treatment-Emergent Adverse Events. 
If there is more than one TEAE within a preferred term (PT), the patient is counted only once in that PT. 
PTs are sorted in descending order of frequency for the overall group. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                        Filename: (Specify file name.rtf) 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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Version 5.0 25Jun2020 
 
 
 
 
Table 14.3-1.7 – Summary of Related Treatment-emergent Adverse Events by Preferred Term 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.6 
 
Present Related TEAE: TEAEs with causality=Related, Possibly Related or missing. 
 
Add footnote: 
“Related TEAE: TEAEs with causality=Related, Possibly Related or missing.” 
 
Table 14.3-1.8 – Summary of Serious Treatment-emergent Adverse Events by Preferred Term 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.6 
 
Present Serious TEAE: TEAEs with SAE =” Yes”. 
 
Add footnote: 
“Serious TEAE: TEAEs with SAE =” Yes”.” 
 
Table 14.3-1.9 – Summary of Related Serious Treatment-emergent Adverse Events by Preferred Term 
 
 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.6 
 
Present Related Serious TEAE: SAEs with causality=Related, Possibly Related or missing. 
 
Add footnote: 
“SAEs with causality=Related, Possibly Related or missing.” 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
 
Table 14.3-1.10 – Summary of Treatment-Emergent Adverse Events by System Organ Class and Preferred Term for Maximum CTCAE Grade 
Safety Analysis Set 
 
Group: Group X 
System Organ Class 
  Preferred Term 
Any CTC Grade 
n (%) [Events] 
CTC Grade 1 
n (%) 
CTC Grade 2 
n (%) 
CTC Grade 3 
n (%) 
CTC Grade 4 
n (%) 
CTC Grade 5 
n (%) 
 
 
 
 
 
 
Any TEAE 
XX (XX.X) [XX] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
System organ class 1 
XX (XX.X) [XX] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 1 
XX (XX.X) [XX] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 2 
XX (XX.X) [XX] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) [XX] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
System organ class 2 
XX (XX.X) [XX] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 1 
XX (XX.X) [XX] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 2 
XX (XX.X) [XX] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) [XX] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Note: MedDRA <vx.x>; CTCAE v5.0. TEAE=Treatment-Emergent Adverse Events. 
If there is more than one TEAE within a system organ class (SOC), the patient is counted only once under that SOC and maximum severity. 
If there is more than one TEAE within a SOC and preferred term (PT), the patient is counted only once in that SOC, PT and maximum severity. 
Primary SOCs are presented by descending order of frequency for the overall group, PTs are sorted within primary SOC descending order of 
frequency for the overall group within each SOC. 
[Events] presents the number of TEAEs reported overall, by primary SOC and PT regardless of severity. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
Present for each group and overall. 
 
 


 
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Table 14.3-1.11 – Summary of Related Treatment-Emergent Adverse Events by System Organ Class and Preferred Term  
for Maximum CTCAE Grade 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.10 
 
Present Related TEAE: TEAEs with causality=Related, Possibly Related or missing. 
 
Add footnote: 
“Related TEAE: TEAEs with causality=Related, Possibly Related or missing.” 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
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Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
 
Table 14.3-1.12 – Summary of Treatment-Emergent Adverse Events Leading to Treatment Discontinuation 
by System Organ Class and Preferred Term 
Safety Analysis Set 
 
System Organ Class 
  Preferred Term 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
Any TEAE leading to treatment 
discontinuation 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
System organ class 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
System organ class 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: MedDRA <vx.x>. TEAE=Treatment-Emergent Adverse Events. 
If there is more than one TEAE leading to treatment discontinuation within a system organ class (SOC), the patient is counted only once under 
that SOC. If there is more than one TEAE leading to treatment discontinuation within a SOC and preferred term (PT), the patient is counted only 
once in that SOC and PT. 
Primary SOCs are presented by descending order of frequency for the overall group, PTs are sorted within primary SOC descending order of frequency 
for the overall group within each SOC. 
TEAEs leading to treatment discontinuation: any TEAEs with Action taken with study treatment=Drug withdrawn. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                        Filename: (Specify file name.rtf) 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 58 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
Table 14.3-1.13 – Summary of Related Treatment-Emergent Adverse Events Leading to Treatment Discontinuation 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Present Related TEAE: TEAEs with causality=Related, Possibly Related or missing. 
 
Add footnote: 
“Related TEAE: TEAEs with causality=Related, Possibly Related or missing.” 
 
Table 14.3-1.14 – Summary of Treatment-Emergent Adverse Events Leading to Treatment Discontinuation Within Cycle 1 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Add footnote: 
“TEAEs leading to treatment discontinuation: any TEAEs with Action taken with study treatment=Drug withdrawn within the first 28 days of study.” 
 
Table 14.3-1.15 – Summary of Related Treatment-Emergent Adverse Events Leading to Treatment Discontinuation Within Cycle 1 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Present Related TEAE: TEAEs with causality=Related, Possibly Related or missing. 
 
Add footnote: 
“TEAEs leading to treatment discontinuation: any TEAEs with Action taken with study treatment=Drug withdrawn within the first 28 days of study.” 
 
 
 


 
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Table 14.3-1.16 – Summary of Treatment-Emergent Adverse Events Leading to Treatment Discontinuation Following Cycle 1 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Add footnote: 
“TEAEs leading to treatment discontinuation: any TEAEs with Action taken with study treatment=Drug withdrawn after the first 28 days of study.” 
“Related TEAE: TEAEs with causality=Related, Possibly Related or missing.” 
 
Table 14.3-1.17 – Summary of Related Treatment-Emergent Adverse Events Leading to Treatment Discontinuation Following Cycle 1 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Present Related TEAE: TEAEs with causality=Related, Possibly Related or missing.’ 
 
Add footnote: 
“TEAEs leading to treatment discontinuation: any TEAEs with Action taken with study treatment=Drug withdrawn after the first 28 days of study.” 
“Related TEAE: TEAEs with causality=Related, Possibly Related or missing.” 
 
 
 


 
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Table 14.3-1.18 – Summary of Treatment-Emergent Adverse Events Leading to Treatment Interruption 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Replace ‘Any TEAE’ by ‘Any TEAE leading to treatment interruption.’ 
 
Add footnote: 
 
“Includes TEAE with ‘Action Taken with treatment’ = ‘Dose Interrupted’. 
 
Table 14.3-1.19 – Summary of Related Treatment-Emergent Adverse Events Leading to Treatment Interruption 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Replace ‘Any TEAE’ by ‘Any related TEAE leading to treatment interruption.’ 
 
Add footnotes: 
“Includes TEAE with ‘Action Taken with treatment’ = ‘Dose Interrupted’. 
“Related TEAE: TEAEs with causality=Related, Possibly Related or missing.” 
 
 
 


 
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Statistical Analysis Plan:  
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Table 14.3-1.20 – Summary of Treatment-Emergent Adverse Events Leading to Treatment Interruption Within Cycle 1 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Replace ‘Any TEAE’ by ‘Any TEAE leading to treatment interruption within Cycle 1.’ 
 
Add footnote: 
“Includes TEAE with ‘Action Taken with treatment’ = ‘Dose Interrupted’ within the first 28 days of study. 
 
Table 14.3-1.21 – Summary of Related Treatment-Emergent Adverse Events Leading to Treatment Interruption Within Cycle 1 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Replace ‘Any TEAE’ by ‘Any related TEAE leading to treatment interruption within Cycle 1.’ 
 
Add footnotes: 
“Includes TEAE with ‘Action Taken with treatment’ = ‘Dose Interrupted’ after the first 28 days of study. 
 
 
 
 


 
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Table 14.3-1.22 – Summary of Related Treatment-Emergent Adverse Events Leading to Treatment Interruption Following Cycle 1 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Replace ‘Any TEAE’ by ‘Any TEAE leading to treatment interruption following Cycle 1.’ 
 
Add footnote: 
“Includes TEAE with ‘Action Taken with treatment’ = ‘Dose Interrupted’ after the first 28 days of study. 
“Related TEAE: TEAEs with causality=Related, Possibly Related or missing.” 
 
Table 14.3-1.23 – Summary of Related Treatment-Emergent Adverse Events Leading to Treatment Interruption Following Cycle 1 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Replace ‘Any TEAE’ by ‘Any related TEAE leading to treatment interruption following Cycle 1’. 
 
Add footnotes: 
“Includes TEAE with ‘Action Taken with treatment’ = ‘Dose Interrupted’ after the first 28 days of study. 
“Related TEAE: TEAEs with causality=Related, Possibly Related or missing.” 
 
 


 
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Table 14.3-1.24 – Summary of Treatment-Emergent Adverse Events Leading to Dose Reduction  
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Replace ‘Any TEAE’ by ‘Any TEAE leading to dose reduction.’ 
 
Add footnote: 
“Includes TEAE with ‘Action Taken with treatment’ = ‘Dose Reduced’”. 
 
 
Table 14.3-1.25 – Summary of Related Treatment-Emergent Adverse Events Leading to Dose Reduction  
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Replace ‘Any TEAE’ by ‘Any related TEAE leading to dose reduction.’ 
 
Add footnotes: 
“Includes TEAE with ‘Action Taken with treatment’ = ‘Dose Reduced’”. 
“Related TEAE: TEAEs with causality=Related, Possibly Related or missing.” 
 
 
 


 
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Table 14.3-1.26 – Summary of Treatment-Emergent Adverse Events Leading to Dose Reduction within Cycle 1 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Replace ‘Any TEAE’ by ‘Any TEAE leading to dose reduction within Cycle 1.’ 
 
Add footnote: 
“Includes TEAE with ‘Action Taken with treatment’ = ‘Dose Reduced’ within the first 28 days of study”. 
 
 
Table 14.3-1.27 – Summary of Related Treatment-Emergent Adverse Events Leading to Dose Reduction within Cycle 1 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Replace ‘Any TEAE’ by ‘Any related TEAE leading to dose reduction within Cycle 1.’ 
 
Add footnotes: 
“Includes TEAE with ‘Action Taken with treatment’ = ‘Dose Reduced’ within the first 28 days of study”. 
“Related TEAE: TEAEs with causality=Related, Possibly Related or missing.” 
 
 
 


 
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Statistical Analysis Plan:  
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Table 14.3-1.28 – Summary of all Treatment-Emergent Adverse Events Leading to Dose Reduction following Cycle 1 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Replace ‘Any TEAE’ by ‘Any TEAE leading to dose reduction following Cycle 1. 
 
Add footnote: 
“Includes TEAE with ‘Action Taken with treatment’ = ‘Dose Reduced’ after the first 28 days of study”. 
 
Table 14.3-1.29 – Summary of Related Treatment-Emergent Adverse Events Leading to Dose Reduction following Cycle 1 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.12 
 
Replace ‘Any TEAE’ by ‘Any related TEAE leading to dose reduction following Cycle 1. 
 
Add footnote: 
“Includes TEAE with ‘Action Taken with treatment’ = ‘Dose Reduced’ after the first 28 days of study”. 
“Related TEAE: TEAEs with causality=Related, Possibly Related or missing.” 
 
 


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
 
Table 14.3-1.30 – Summary of Treatment-Emergent Adverse Events Leading to Death by System Organ Class and Preferred Term 
Safety Analysis Set 
 
System Organ Class 
  Preferred Term 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
Any TEAE leading to death 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
System organ class 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
System organ class 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Preferred term 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  ………… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: MedDRA <vx.x>. TEAE=Treatment-Emergent Adverse Events. 
If there is more than one TEAE leading to death within a system organ class (SOC), the patient is counted only once under that SOC. If there is 
more than one TEAE leading to death within a SOC and preferred term (PT), the patient is counted only once in that SOC and PT. 
Primary SOCs are presented by descending order of frequency for the overall group, PTs are sorted within primary SOC descending order of frequency 
for the overall group within each SOC. 
TEAEs leading to Death: any TEAE resulting in death, Outcome=Fatal, CTC Grade=5. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                        Filename: (Specify file name.rtf) 
 


 
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Table 14.3-1.31 – Summary of Related Treatment-Emergent Adverse Events Leading to Death by System Organ Class and Preferred Term 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-1.20 
 
Present Related TEAE: TEAEs with causality=Related, Possibly Related or missing. 
 
Add footnote: 
“Related TEAE: TEAEs with causality=Related, Possibly Related or missing.” 
 
 


 
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Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-1.32 – Summary of Deaths 
All Patients Set 
 
 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Screen 
Failures 
N=XX 
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
 
Patients who died during the 
study 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
Primary cause of death 
 
 
 
 
 
 
 
 
  Progressive Disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Adverse Event 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Unknown 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
Patients who died after 
taking the first dose of 
ulixertinib 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
Primary cause of death 
 
 
 
 
 
 
 
 
  Progressive Disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Adverse Event 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  Unknown 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-2.1 – Summary and Change from Baseline in Hematology Laboratory Results by Visit 
Safety Analysis Set 
 
Parameter: XXXXX (XX) 
Visit 
   Statistics 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
Baseline  
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
C1D8  
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
Change from Baseline to C1D8  
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Baseline is the last available assessment prior to first dose of study treatment. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                 Filename: (Specify file name.rtf) 
 
 


 
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PROGRAMMING NOTES: 
 
Present for all hematology parameters: hematocrit, hemoglobin, platelets, red blood cells (RBC), white blood cells (WBC), neutrophil absolute, basophil 
absolute, monocyte absolute, lymphocyte absolute and eosinophil absolute with respective unit measure. 
 
Present for all available visits. 
 
 


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-2.2.1 – Gradable Hematology Laboratory Results – Worst On-treatment Value by Cycle 
Safety Analysis Set 
 
Parameter (unit) 
  Cycle 
    CTCAE Grade 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
XXXXX (XXX) 
 
 
 
 
 
 
 
  Cycle 1 
 
 
 
 
 
 
 
    Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
  Cycle 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: CTCAE v5.0. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                 Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Present for all hematology parameters where CTCAE grades are defined as per the SAP appendix 14.2. 
 
 
 


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-2.2.2 – Non-gradable Hematology Laboratory Results – Worst On-treatment Value by Cycle 
Safety Analysis Set 
 
Parameter (unit) 
  Cycle 
    CTCAE Grade 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
XXXXX (XXX) 
 
 
 
 
 
 
 
  Cycle 1 
 
 
 
 
 
 
 
    Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Low 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    High 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
  Cycle 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Low 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    High 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Missing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: CTCAE v5.0. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                 Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Present for all hematology parameters where CTCAE grades are not defined as per the SAP appendix 14.2. 
 
 


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-2.3.1 – Shift Table of Gradable Hematology Laboratory Results – Baseline vs Worst On-treatment Value 
Safety Analysis Set 
 
Part A 
Group: Group 1 
 
 
Worst CTCAE grade during treatment period 
 
Parameter 
(unit) 
Baseline 
Grade 
Normal 
n (%) 
1 
n (%) 
2 
n (%) 
3 
n (%) 
4 
n (%) 
Missing 
n (%) 
Total 
n (%) 
 
 
 
 
 
 
 
 
XXXXX 
Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
(XXX) 
1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
Note: CTCAE v5.0. 
Baseline is the last available assessment prior to first dose of study treatment. 
Percentages are based on the number of patients in the group. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Present for each group and overall, and for all hematology parameters where CTCAE grades are defined as per the SAP appendix 14.2. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 74 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-2.3.2 – Shift Table of Non-gradable Hematology Laboratory Results – Baseline vs Worst On-treatment Value 
Safety Analysis Set 
 
Part A 
Group: Group 1 
 
 
Worst grade during treatment period 
 
Parameter 
(unit) 
Baseline 
Grade 
Low 
n (%) 
Normal 
n (%) 
High 
n (%) 
Missing 
n (%) 
Total 
n (%) 
 
 
 
 
 
 
XXXXX 
Low 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
(XXX) 
Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
High 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
Note: Baseline is the last available assessment prior to first dose of study treatment. 
Percentages are based on the number of patients in the group. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Present for all groups and overall, and for all hematology parameters where CTCAE grades are not defined as per the SAP appendix 14.2. 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
Table 14.3-2.4 – Summary and Change from Baseline in Biochemistry Laboratory Results by Visit 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.3-2.1 
 
Present for all biochemistry parameters: alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, blood urea nitrogen, 
calcium, chloride, cholesterol, creatinine, direct bilirubin, glucose, indirect bilirubin, inorganic phosphorus, lactate dehydrogenase, potassium, total 
protein, sodium, total bilirubin, triglycerides, uric acid. 
 
Present for all available visits. 
 
 
Table 14.3-2.5.1 – Gradable Biochemistry Laboratory Results – Worst On-treatment Value by Cycle 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat of Table 14.3-2.2.1 
 
Present for all biochemistry parameters where CTCAE grades are defined as per the SAP appendix 14.2. 
 
Table 14.3-2.5.2 – Non-gradable Biochemistry Laboratory Results – Worst On-treatment Value by Cycle 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat of Table 14.3-2.2.2 
 
Present for all biochemistry parameters where CTCAE grades are defined as per the SAP appendix 14.2. 
 
Table 14.3-2.6.1 – Shift Table of Gradable Biochemistry Laboratory Results – Baseline vs Worst On-treatment Value 
Safety Analysis Set 
 
 
PROGRAMMING NOTES: 
 
Repeat of Table 14.3-2.3.1 
 
Present for all groups and overall, and for all biochemistry parameters where CTCAE grades are defined as per the SAP appendix 14.2. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 76 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
Table 14.3-2.6.2 – Shift Table of Non-gradable Biochemistry Laboratory Results – Baseline vs Worst On-treatment Value 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat of Table 14.3-2.3.2 
 
Present for all groups and overall, and for all biochemistry parameters where CTCAE grades are not defined as per the SAP appendix 14.2. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 77 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-2.7 – Summary and Change from Baseline in Urinalysis Laboratory Results by Visit 
Safety Analysis Set 
 
Parameter: Specific gravity (XX) 
Visit 
   Statistics 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
Baseline  
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
C1D8  
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
Change from Baseline to C1D8  
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Baseline is the last available assessment prior to first dose of study treatment. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                 Filename: (Specify file name.rtf) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 2 of Y   
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-2.7 – Summary and Change from Baseline in Urinalysis Laboratory Results by Visit 
Safety Analysis Set 
 
Parameter: Blood (XX) 
Visit 
   Statistics 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
Baseline  
 
 
 
 
 
 
 
   Negative 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   1+ 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   2+ 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   3+ 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   4+ 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
C1D1  
 
 
 
 
 
 
 
   Negative 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   1+ 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   2+ 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   3+ 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   4+ 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
<cont.> 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Baseline is the last available assessment prior to first dose of study treatment. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                 Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
present for all urinalysis parameters: specific gravity, pH, dipstick evaluation of glucose, dipstick evaluation of protein, dipstick evaluation of 
bilirubin, dipstick evaluation of ketones, dipstick evaluation of leukocytes, dipstick evaluation of blood, microscopic examination of RBC, 
microscopic examination of WBC, microscopic examination of casts. 
 
Present for all available visits. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 79 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-3.1 – Summary and Change from Baseline in Vital Signs by Visit 
Safety Analysis Set 
 
Parameter: XXXXX (XX) 
Visit 
  Statistics 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
Baseline  
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
C1D8  
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
Change from Baseline to C1D8  
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
Note: Baseline is the last available assessment prior to first dose of study treatment. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                 Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Present for all vital signs: systolic blood pressure, diastolic blood pressure, pulse and temperature with respective unit measure.  
 
Present for all available visits. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 80 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-3.2 – Shift Table of Vital Signs Results – Baseline vs Worst On-treatment Value 
Safety Analysis Set 
 
Group: Group 1 
 
 
Worst value during on-treatment period 
 
Parameter 
(unit) 
Baseline 
Value 
Low 
n (%) 
Normal 
n (%) 
High 
n (%) 
Very High 
n (%) 
Missing 
n (%) 
Total 
n (%) 
 
 
 
 
 
 
 
XXXXX 
Low 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
(XXX) 
Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
High 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Very High 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Note: Baseline is the last available assessment prior to first dose of study treatment. 
Percentages are based on the number of patients in the group. 
For Temperature, Low: < 36.4°C, Normal: 36.4°C - 37.7°C, High: > 37.7°C. 
For Pulse, Low: < 55 bpm, Normal: 55-100 bpm, High: 101-150 bpm, Very high: > 150 bpm. 
For Systolic blood pressure, Low: < 90 mmHg, Normal: 90-130 mmHg, High: 131-160 mmHg, Very high: ≥ 161 mmHg. 
For Diastolic blood pressure, Low: < 60 mmHg, Normal: 60-85 mmHg, High: 86-100 mmHg, Very high: ≥ 101 mmHg. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
Present for each group and overall, and for all vital signs parameters. 
 
 
 
 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y  
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 81 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
Data extraction date: DDMMMYYYY 
Table 14.3-3.3 – Summary of ECG at Baseline 
Safety Analysis Set 
 
 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
Heart Rate  
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
PR Interval  
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
QRS Duration 
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
Note: Baseline is the last available assessment prior to first dose of study treatment. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                 Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
Present for all ECG parameters: heart rate, PR interval, QRS duration, RR interval, QT interval, QTcF with respective unit measure.  
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 82 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y  
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-3.4 – Summary of ECHO/MUGA at Baseline 
Safety Analysis Set 
 
 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Method – n (%) 
 
 
 
 
 
 
 
   Echocardiography 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   MUGA 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Significant findings – n (%) 
 
 
 
 
 
 
 
   Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
LVEF 
 
 
 
 
 
 
 
   n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
   Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
   Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
   Min; Max 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
XX; XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Baseline is the last available assessment prior to first dose of study treatment. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                 Filename: (Specify file name.rtf) 
 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 83 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y  
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-3.5 – Summary of Physical Examination at Baseline 
Safety Analysis Set 
 
 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
HEENT 
 
 
 
 
 
 
 
   Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Abnormal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Not Done 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Thorax 
 
 
 
 
 
 
 
   Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Abnormal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Not Done 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
Abdomen 
 
 
 
 
 
 
 
   Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Abnormal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   Not Done 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
<cont.> 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Baseline is the last available assessment prior to first dose of study treatment. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                 Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
Present for all Region/Body System parameters: HEENT, thorax, abdomen, skin and mucosae, neurological, extremities, urogenital, general 
appearance, heart, back, lymph nodes. 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 84 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y  
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.3-3.6 – Summary of ECOG Performance Status by Visit 
Safety Analysis Set 
 
Visit 
   Grade 
Group 1 
N=XX  
n (%) 
Group 2 
N=XX  
n (%) 
Group 3 
N=XX  
n (%) 
Group 4 
N=XX  
n (%) 
Group 5 
N=XX  
n (%) 
Group 6 
N=XX  
n (%) 
Overall 
N=XX  
n (%) 
 
 
 
 
 
 
 
 
Baseline [a] 
 
 
 
 
 
 
 
   0 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C1D8 [a] 
 
 
 
 
 
 
 
   0 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   5 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
C1D15 [a] 
 
 
 
 
 
 
 
   ………… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
   <cont.> 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Baseline is the last available assessment prior to first dose of study treatment. 
[a] (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 self-care but unable to carry out any work activities 
    (3) Capable of only limited selfcare; confined 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) Death 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                 Filename: (Specify file name.rtf) 
PROGRAMMING NOTES: 
 
Present for all available visits. 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y   
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.5-1.1 – Pharmacokinetic Data 
Full Analysis Set 
 
Visit 
 Analyte 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cycle X Day Y 
 
 
 
 
 
 
 
BVD-523 (ng/mL) 
 
 
 
 
 
 
 
 n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 Mean (SD) 
XX.XX (XX.XX) 
XX.XX (XX.XX) XX.XX (XX.XXX) XX.XX (XX.XX) XX.XX (XX.XX) XX.XX (XX.XX) XX.XX (XX.XX) 
 Geometric Mean (CV) 
XX.XX (XX.XX) 
XX.XX (XX.XX) XX.XX (XX.XXX) XX.XX (XX.XX) XX.XX (XX.XX) XX.XX (XX.XX) XX.XX (XX.XX) 
 Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 Min; Max 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CV=Coefficient of Variation, SD=Standard Deviation 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.doc) 
 
PROGRAMMING NOTES: 
 
Present for all available analytes (BVD-523, BVD-502/503,BVD-506, BVD-513) and visits 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 86 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
Table 14.5-1.2 – Pharmacokinetic Data 
Per Protocol Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.5-1.1 
 
Present data on Per Protocol Set. 
 
For Part B only 
Table 14.5-1.3 – Pharmacokinetic Data 
Evaluable Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Table 14.5-1.1 
 
Present data on Evaluable Analysis Set. 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 87 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y      
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Table 14.6-1.1 – Blood Pharmacodynamic Data 
Full Analysis Set 
 
Visit 
 Analyte 
Group 1 
N=XX 
Group 2 
N=XX 
Group 3 
N=XX 
Group 4 
N=XX 
Group 5 
N=XX 
Group 6 
N=XX 
Overall 
N=XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cycle X Day Y 
 
 
 
 
 
 
 
% inhibition (simplified to 
0-100%) 
 
 
 
 
 
 
 
 n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 Mean (SD) 
XX.XX (XX.XX) 
XX.XX (XX.XX) XX.XX (XX.XXX) XX.XX (XX.XX) XX.XX (XX.XX) XX.XX (XX.XX) XX.XX (XX.XX) 
 Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 Min; Max 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
XX.X; XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
GSD=Geometric Standard Deviation, SD=Standard Deviation 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.doc) 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 88 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Figure 14.2-1.1 – Consort Diagram 
Full Analysis Set 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                        Filename: (Specify file name.rtf)                        
  
 
 
Enrollment 
Assessed for eligibility (n=) 
Enrolled (n=) 
Excluded (n=), reasons: 
           Adverse Event (n=) 
           Death (n=) 
           Pregnancy (n=) 
           Screen Failure (n=) 
           Study Terminated by Sponsor (n=) 
           Lost to Follow-up (n=) 
           Technical Problems (n=) 
           Physician Decision (n=) 
           Withdrawal by Patient (n=) 
           Other (n=) 
Allocation 
Follow-Up 
Discontinued treatment (n=), reasons: 
           Death (n=) 
           Progressive Disease (n=) 
           Adverse Event (n=) 
           Pregnancy (n=) 
           Withdrawal by Patient (n=) 
           Protocol Violation (n=) 
           Lost to Follow-up (n=) 
           Physician Decision (n=) 
           Study Terminated by Sponsor (n=) 
           Other (n=) 
Analysis 
Analysed in Safety Analysis Set (n=) 
 
Excluded from Analysis (n=) 
Allocated to Group 1 (n=xx) 
 
Received allocated 
Intervention (n=xx) 
 
Did not receive 
allocated 
intervention (n=xx) 
Allocated to Group 2 (n=xx) 
 
Received allocated 
Intervention (n=xx) 
 
Did not receive 
allocated 
intervention (n=xx) 
Allocated to Group 3 (n=xx) 
 
Received allocated 
Intervention (n=xx) 
 
Did not receive 
allocated 
intervention (n=xx) 
Allocated to Group 4 (n=xx) 
 
Received allocated 
Intervention (n=xx) 
 
Did not receive 
allocated 
intervention (n=xx) 
Allocated to Group 5 (n=xx) 
 
Received allocated 
Intervention (n=xx) 
 
Did not receive 
allocated 
intervention (n=xx) 
Allocated to Group 6 (n=xx) 
 
Received allocated 
Intervention (n=xx) 
 
Did not receive 
allocated 
intervention (n=xx) 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 89 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Figure 14.2-1.2.1 – Spider plot of Percentage Change from Baseline in Sum of Longest Diameter 
Full Analysis Set 
 
 
Group = Group X 
 
 
 
                                        Weeks since Treatment Initiation 
 
Best overall response: CR=Complete Response, PR=Partial Response, SD=Stable Disease, PD=Progression Disease, NE=Not Evaluable. 
  
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                        Filename: (Specify file name.rtf)                        
  
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 90 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
 
Figure 14.2-1.2.2 – Spider plot of Percentage Change from Baseline in Sum of Longest Diameter 
Per Protocol Set 
 
PROGRAMMING NOTES: 
 
Repeat Figure 14.2-1.2.1 
 
Present data on Per Protocol Set. 
Figure 14.2-1.2.3 – Spider plot of Percentage Change from Baseline in Sum of Longest Diameter 
Evaluable Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Figure 14.2-1.2.1 
 
Present data on Evaluable Analysis Set. 
 
 
PROGRAMMING NOTES: 
 
Present all groups from Part A in separate figures and one figure with all patients. 
 
Use a different color style for each BOR separately (CR/PR/SD/PD/NE).  
 
Add reference lines for +20% and -30%. 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 91 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Figure 14.2-1.3.1 – Waterfall plot of Maximum Percentage Change from Baseline in Sum of Longest Diameter 
Full Analysis Set 
 
Group = Group X 
 
 
Maximum percentage change from baseline in total tumor size is the maximum percent change in the sum of longest diameters/short axis for 
all target lesions observed from baseline for each patient.  
 
Best overall response: CR=Complete Response, PR=Partial Response, SD=Stable Disease, PD=Progression Disease, NE=Not Evaluable. 
  
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                        Filename: (Specify file name.rtf)                        
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 92 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
 
Figure 14.2-1.3.2 – Waterfall plot of Maximum Percentage Decrease from Baseline in Sum of Longest Diameter 
Per Protocol Set 
 
PROGRAMMING NOTES: 
 
Repeat Figure 14.2-1.3.1 
 
Present data on Per Protocol Set. 
Figure 14.2-1.3.3 – Waterfall plot of Maximum Percentage Decrease from Baseline in Sum of Longest Diameter 
Evaluable Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Figure 14.2-1.3.1 
 
Present data on Evaluable Analysis Set. 
 
 
PROGRAMMING NOTES: 
 
Present each group from Part A on one figure and one figure with all patients. 
 
Each bar is an individual patient. 
 
Add reference lines for +20% and -30%. 
 
Add the best overall response (CR, PR, SD, PD, NE) of each patient on the top of each bar. 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 93 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Figure 14.2-1.4.1 – Swimmer Plot of Response Assessments 
Full Analysis Set 
 
 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                        Filename: (Specify file name.rtf)                        
 
 
j
(
)
Individual Patients
Weeks Since Treatment Initiation
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100
105
110
115
120
125
130
0060001
0080002
0050004
0070004
0040001
0070003
0020017
0090001
0060003
0030002
0020011
0020015
0050002
0050003
0090005
0100001
0010011
0070002
0070005
0010008
0020012
0010015
0020010
0020016
00500080080004
0010014
0050006
0050007
0090002
0090006
0090004
0080001
0060002
0070006
0110001
0010016
0030001
0010009
0080003
Complete response
Partial response
Progessive disease
Death
Ongoing response
End of Treatment


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 94 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
 
Figure 14.2-1.4.2 – Swimmer Plot of Response Assessments 
Per Protocol Set 
 
PROGRAMMING NOTES: 
 
Repeat Figure 14.2-1.4.1 
 
Present data on Per Protocol Set. 
Figure 14.2-1.4.3 – Swimmer Plot of Response Assessments 
Evaluable Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Figure 14.2-1.4.1 
 
Present data on Evaluable Analysis Set. 
 
 
PROGRAMMING NOTES: 
 
Present each group from Part A on one figure and a figure including all patients. 
 
Display patient ID on the left outside the figure. 
 
The bar displays time to PD/Death (PFS), with “PD” or “death” displayed at the end of the bar; if no PD/death occurred before cutoff date, the bar 
stops at cutoff date.  
 
For responders, display the date of first CR or PR, and display “Ongoing response” arrow if no PD or death occurred before cutoff date. 
 
“End of Treatment” is the date of treatment discontinuation, this must be displayed only for patients who discontinued the treatment before the 
cut-off date. 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 95 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Figure 14.2-1.5.1 – Kaplan-Meier Estimate for Duration of Response 
Full Analysis Set 
 
 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                        Filename: (Specify file name.rtf)                        
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 96 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
PROGRAMMING NOTES:  
 
X-axis – Label “Duration of Response (months)”  
 
Y-axis – Label “Event-free probability (%).”  
 
Legend: overall number of events, “Median Duration of Response” and 95% CI.   
 
Flag censored observations with ‘+’ and add legend.  
 
If the median time to event has not been reached, present as “Median (95% CI) NR (xx.x, xx.x)” [replacing xx.x with ‘-‘ if there is no upper or lower 
confidence limit] and add footnote: 
NR=Median time not reached. 
 
For Part A, present all groups on the same figure but with different colors and separate figures for each group. 
 
 
Figure 14.2-1.5.2 – Kaplan-Meier Estimate for Duration of Response 
Per Protocol Set 
 
PROGRAMMING NOTES: 
 
Repeat Figure 14.2-1.5.1 
 
Present data on Per Protocol Set. 
 
Figure 14.2-1.5.3 – Kaplan-Meier Estimate for Duration of Response 
Evaluable Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Figure 14.2-1.5.1 
 
Present data on Evaluable Analysis Set. 
 
Figure 14.2-1.6.1 – Kaplan-Meier Estimate for Progression-Free survival (PFS) 
Full Analysis Set 
 
PROGRAMMING NOTES: 
 
Replicate figure 14.2-1.5.1, replacing “Duration of Response” by “Progression Free Survival” in X-axis label and legend. 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 97 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
Figure 14.2-1.6.2 – Kaplan-Meier Estimate for Progression-Free survival (PFS) 
Per Protocol Set 
 
PROGRAMMING NOTES: 
 
Replicate figure 14.2-1.5.1, replacing “Duration of Response” by “Progression Free Survival” in X-axis label and legend. 
 
Present data on Per Protocol Set. 
 
Figure 14.2-1.6.3 – Kaplan-Meier Estimate for Progression-Free survival (PFS) 
Evaluable Analysis Set 
 
PROGRAMMING NOTES: 
 
Replicate figure 14.2-1.5.1, replacing “Duration of Response” by “Progression Free Survival” in X-axis label and legend. 
 
Present data on Evaluable Analysis Set. 
 
 
 
Figure 14.2-1.7.1 – Kaplan-Meier Estimate for Overall Survival  
Full Analysis Set 
 
PROGRAMMING NOTES: 
 
Replicate figure 14.2-1.5.1, replacing “Duration of Response” by “Overall Survival” in X-axis label and legend. 
 
 
Figure 14.2-1.7.2 – Kaplan-Meier Estimate for Overall Survival  
Per Protocol Set 
 
PROGRAMMING NOTES: 
 
Replicate figure 14.2-1.5.1, replacing “Duration of Response” by “Overall Survival” in X-axis label and legend. 
 
Present data on Per Protocol Set. 
Figure 14.2-1.7.3 – Kaplan-Meier Estimate for Overall Survival  
Evaluable Analysis Set 
 
PROGRAMMING NOTES: 
 
Replicate figure 14.2-1.5.1, replacing “Duration of Response” by “Overall Survival” in X-axis label and legend. 
 
Present data on Evaluable Analysis Set. 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 98 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.1-1 – Patients informed consent 
All Patients Set 
 
 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
 
 
 
Protocol 
Version 
Main Informed Consent 
Sample banking for future 
Biospecimen research consent 
Optional End of Treatment 
Biopsy 
Pregnancy and Pregnant 
Partner 
Consent 
Obtained / 
Withdrawn? 
Date Consent  
Obtained / 
Withdrawn 
Consent 
Obtained / 
Withdrawn? 
Date Consent  
Obtained / 
Withdrawn 
Consent 
Obtained / 
Withdrawn? 
Date Consent  
Obtained / 
Withdrawn 
Consent 
Obtained? 
Date Consent 
Obtained / 
Withdrawn 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XX/M 
1.0 
Yes / Yes 
DDMMMYYYY / 
DDMMMYYYY 
Yes 
DDMMMYYYY / 
DDMMMYYYY 
Yes 
DDMMMYYYY / 
DDMMMYYYY 
Yes 
DDMMMYYYY / 
DDMMMYYYY 
XXXXXX 
XX/F 
1.0 
Yes / No 
DDMMMYYYY 
Yes 
DDMMMYYYY 
Yes 
DDMMMYYYY 
Yes 
DDMMMYYYY 
XXXXXX 
XX/F 
1.0 
Yes / No 
DDMMMYYYY 
Yes 
DDMMMYYYY 
Yes 
DDMMMYYYY 
Yes 
DDMMMYYYY 
XXXXXX 
XX/F 
1.0 
No / Yes 
DDMMMYYYY 
DDMMMYYYY 
No 
DDMMMYYYY 
No 
DDMMMYYYY 
No 
DDMMMYYYY 
<cont.> 
 
 
 
 
 
 
 
 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.doc) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 99 of 144 
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Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.1-2 – Failed Inclusion and Exclusion Criteria 
All Patients Set 
Group: Group 1 
Subject  
ID 
Age /  
Gender 
Protocol  
Version 
Failed Inclusion / 
Exclusion No. 
 
Description 
 
 
 
 
 
xxx-xx 
xx/M 
1.0 
INCL01 
 
xxxxxxxxxxxxx 
 
 
 
 
 
xxx-xx 
xx/M 
1.0 
EXCL01 
xxxxxxxxxxxxx 
 
 
 
 
 
xxx-xx 
xx/M 
1.0 
EXCL02 
xxxxxxxxxxxxx 
 
 
 
 
 
xxx-xx 
xx/F 
1.0 
INCL02 
xxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                             Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
List all failed Inclusion / Exclusion criteria as per eCRF.  
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.1-3 – Patient Disposition 
All Patients Set 
Group: Group 1 
Subject 
ID 
Age / 
Gender  Enrolled 
Date of 
Assignment 
Gene/ Codon/ 
Amino acid 
change 
Completed 
Screening / 
Reason 
Date of 
Screening 
Completion / 
Discontinuation  
Eligible for  
inclusion? 
Rescreened? /  
Previous patient 
number 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Yes 
 
DDMMMYYYY 
BRAF /D594 / 
Alanine A 
Yes 
DDMMMYYYY 
Yes 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Yes 
 
DDMMMYYYY 
MEK1/MAP2K1 / 
K601 /Arginine R 
No / 
Physician 
Decision 
DDMMMYYYY 
Yes 
Yes /xxxxxxx 
 
 
 
 
 
 
 
 
 
Enrolled patients are patients that fullfill all selection criterion and included in the study to be dosed.  
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                             Filename: (Specify file name.rtf) 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
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BioMed Valley Discoveries                                                                                                Page 2 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
 
Listing 16.2.1-3 – Patient Disposition 
All Patients Set 
 
Group: Group 1 
Subject 
ID 
Age / 
Gender  
Completed 
Treatment / 
Reason 
Date of Treatment 
Discontinuation 
Date of Last Study 
Dose 
Completed Study / 
If no, reason 
Date of Completion (Follow-up) 
/ Discontinuation from Study 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Yes 
DDMMMYYYY 
DDMMMYYYY 
Yes 
 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
No/ 
Progressive 
Disease 
 
DDMMMYYYY 
DDMMMYYYY 
No/ xxxxxx 
 
Yes 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                             Filename: (Specify file name.rtf) 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part B 
Data extraction date: DDMMMYYYY 
Listing 16.2.1-4 – Randomization 
Full Analysis Set 
 
Subject ID 
Randomization Number 
Allocated treatment 
  
 
 
 
 
 
xxx-xx 
xxxxx 
Ulixertinib - Group 
X 
 
 
 
 
 
 
 
xxx-xx 
xxxxx 
Physician’s Choice 
 
 
 
 
 
 
 
xxx-xx 
xxxxx 
 
 
 
 
 
 
 
 
xxx-xx 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                             Filename: (Specify file name.rtf) 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X  
Data extraction date: DDMMMYYYY 
 
Listing 16.2.2-1 – Analysis Sets 
All Patients Set 
 
Part A 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
All Patients Set [a] 
Full Analysis Set 
[b] 
Safety Analysis Set 
[c] 
Per Protocol 
Analysis Set [d] 
Evaluable Analysis 
Set [e] 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Yes 
Yes 
Yes 
Yes 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Yes 
Yes 
Yes 
Yes 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
[a] Patients who were enrolled regardless of whether they received the study drug or not. 
[b] Patients who received at least 1 dose of the study drug. 
[c] Patients who received at least 1 dose of the study drug. 
[d] All patients from FAS who completed the study without any important protocol deviations. 
[e] All patients from FAS who had the first efficacy evaluation on Study Day 29+3 and completed the study without any important protocol 
deviations. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.3-1 – Protocol Deviations 
Full Analysis Set 
Group: Group 1 
Subject  
ID 
Age /  
Gender 
Deviation 
Category 
Summary Term 
Deviation  
Description 
 
Important? 
Exclusion from Analysis 
Sets 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Inclusion 
Criteria 
xxxxxxxxxxxxx 
xxxxxxxxxxxxx 
Non-Important 
Safety Analysis Set 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Study 
Assessments 
xxxxxxxxxxxxx 
xxxxxxxxxxxxx 
Important 
Full Analysis Set 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                             Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
Categories / Summary Term / Description to match the PDCF. 
 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.4-1 – Demographics and Baseline Characteristics 
Full Analysis Set 
 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
Childbearing/ 
Reproductive 
Potential  
 
Surgery 
Name 
Date of 
Surgery/Post-
Menopausal 
Date of Last 
Menstrual 
Period 
Race 
Ethnicity 
Height at 
Screening 
(cm) 
Weight at 
Screening 
(kg) 
BMI at 
Screening 
(kg/m^2) [a] 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Surgically 
Sterile 
Vasectomy 
DDMMMYYY 
 
White 
Hispanic or 
Latino 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Able to Bear 
Children  
 
 
DDMMMYYY 
Other, 
xxxx 
Not 
Hispanic or 
Latino 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Sterile - 
Other Reason, 
xxxxxx 
 
 
DDMMMYYY 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
[a] Body Mass Index (BMI)=Weight (kg)/ Height(m)^2. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                                   Filename: (Specify file name.rtf) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.4-2 – Smoking History 
Full Analysis Set 
 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
Smoking  
History? 
Substance 
Usage 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Yes 
Cigarettes 
Former 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.4-3 – Disease History 
Full Analysis Set 
 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
Cancer 
Diagnosis 
Date of 
Initial 
Diagnosis  
Time since 
Initial 
Diagnosis [a] 
Stage at 
Diagnosis 
Method of 
Diagnosis 
Current 
Stage at 
Enrollment 
Prior 
Cancer 
Therapies/ 
Regimens? 
Prior 
BRAF/MEK 
Inhibitor 
Therapies? 
 
Prior 
Radiation 
Therapies? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Stomach 
DDMMMYYYY 
xx 
1 
Cytological 
1 
Yes 
No 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Other, 
xxxxx 
DDMMMYYYY 
xx 
2 
Histological 
4 
No 
No 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
[a] Presented in months and calculated as (date of first study treatment - date of diagnosis) / 30.4375. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
For all cases where 'Other’ is present, please present the respective ‘Other’ specification. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.4-4 – Medical History and Concomitant Diseases 
Full Analysis Set 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
Reported Term 
System Organ 
Class 
Preferred Term 
Start Date (Day) 
/End Date (Day) 
Ongoing 
 
MH or Conc. 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
xxxxxxxx 
xxxxxxxxx 
xxxxxxxx 
DDMMMYYYY (xx) / 
DDMMMYYYY (xx) 
No 
 
MH 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
xxxxxxxx 
xxxxxxxxx 
xxxxxxxx 
DDMMMYYYY (xx) 
Yes 
 
Conc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
MedDRA <vx.x>. 
Medical history (MH): any conditions that started before the first study treatment date and were not ongoing at the first study 
treatment date. 
Concomitant disease (Conc.): any conditions that started before first study treatment administration and were ongoing at first study 
treatment administration. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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Version 5.0 25Jun2020 
 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.4-5 – Prior Anti-Cancer Therapies 
Full Analysis Set 
 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
Line of 
Therapy 
Name of 
Therapy 
 
 
Start Date 
(Day) 
End Date 
(Day) 
Best Overall 
Response 
Date of Best 
Overall 
Response 
Date of 
Relapse/ 
Progression 
Reason for 
Discontinuati
on 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
1 
xxxxxx 
 
 
DDMMMYYYY 
(xx) 
DDMMMYYYY 
(xx) 
Stable 
Disease 
DDMMMYYYY 
DDMMMYYYY 
Intolerance 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
1 
xxxxxx 
 
 
DDMMMYYYY 
(xx) 
DDMMMYYYY 
(xx) 
Stable 
Disease 
DDMMMYYYY 
DDMMMYYYY 
Lack of 
Efficacy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
4 
xxxxxx 
 
 
DDMMMYYYY 
(xx) 
DDMMMYYYY 
(xx) 
Partial 
Response 
DDMMMYYYY 
DDMMMYYYY 
Other, 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Data taken from 'Prior Cancer Medications’ page. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.4-6 – Prior BRAF/MEK Inhibitor Therapies 
Full Analysis Set 
 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
Prior BRAF/MEK 
inhibitor 
therapies 
Start Date (Day) 
End Date (Day) 
Best  
Response 
Duration of 
Response (unit) 
Reason for  
Discontinuation 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Vemurafenib 
DDMMMYYYY (xx) 
DDMMMYYYY (xx) 
Stable Disease 
xx (xxx) 
Intolerance 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Dabrafenib 
DDMMMYYYY (xx) 
DDMMMYYYY (xx) 
Stable Disease 
xx (xxx) 
Completed Therapy 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Other, 
xxxx 
DDMMMYYYY (xx) 
DDMMMYYYY (xx) 
Partial Response 
xx (xxx) 
Other, 
xxxxx 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
Data taken from ‘Prior BRAF/MEK inhibitor therapies’ page. 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.4-7 – Prior Radiation Therapies 
Full Analysis Set 
 
Group: Group 1 
Subject  
ID 
Age / 
Gender 
Site of Radiotherapy 
Dose (Unit) 
Start Date (Day) 
End Date (Day) 
Duration 
(months) [a] 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Abdominal Cavity 
xxx (xxx) 
DDMMMYYYY (xx) 
DDMMMYYYY (xx) 
xx 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Adrenal Gland  
xxx (xxx) 
DDMMMYYYY (xx) 
DDMMMYYYY (xx) 
xx 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Bile Duct 
xxx (xxx) 
DDMMMYYYY (xx) 
DDMMMYYYY (xx) 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
[a] Duration of radiotherapy calculated as [(end date – start date) + 1] / 30.4375. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Data taken from 'Prior Radiotherapy’ page. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.4-8 – Prior and Concomitant Medications 
Full Analysis Set 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
Reported Term / 
Preferred Term / 
ATC Class 
Indication 
Start Date 
(Day) 
End  
Date (Day) 
Dose 
(Units) / 
Frequency 
Route 
Medication to 
treat  
adverse event? /  
Adverse Event (ID) 
Ongoing 
 
Prior 
/ 
Conc. 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Xxxxxxxxxxx / 
xxxxxxxxxxxx / 
xxxxxx 
xxxxxx 
DDMMMYYYY 
(xx) 
DDMMMYYYY 
(xx) 
xxx (xx) 
/ Daily 
Oral 
Yes / xxxx (x) 
Yes 
Conc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
xxxxxxxxxxx/ 
xxxxxxxxxxxx / 
xxxxxx 
xxxxxx 
DDMMMYYYY 
(xx) 
Ongoing 
xxx (xx) 
/ Twice 
per day 
Oral, 
xxxx 
No 
No 
Prior 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female, ATC=Anatomical Therapeutic Chemical. 
WHOHD-B3 <vx.x>. 
Prior medication (Prior): any medications whose end date is before the first study treatment date. 
Concomitant medication (Conc.): any medication whose start or end date is either the same or after the first dose of study treatment 
and up to the end of the on-treatment period. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                             Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Data taken from ‘Prior and Concomitant Medications’ page.  
 
Adverse Event ID taken from collected ID. 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 113 of 144 
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Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.4-9 – On Treatment Radiation 
Full Analysis Set 
Cohort: Group 1 
Subject 
ID 
Age / 
Gender 
Received 
Radiation? 
Site of  
Radiotherapy 
Dose (Unit) 
Start Date (Day) 
End Date (Day) 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Yes 
Abdominal Cavity 
xxx (xxx) 
DDMMMYYYY (xx) 
DDMMMYYYY (xx) 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Yes 
Adrenal Gland  
xxx (xxx) 
DDMMMYYYY (xx) 
DDMMMYYYY (xx) 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Data taken from ‘On Treatment Radiation’ page. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.4-10 – On Treatment Surgery and Medical Procedures 
Full Analysis Set 
Cohort: Group 1 
 
Subject  
ID 
 
Age / 
Gender 
 
Any Surgeries/ 
Procedures 
Name of Surgery/  
Procedure 
 
 
Indication? 
Start Date (Day) 
End Date (Day) 
Ongoing? 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Yes 
xxxxxxxxxx 
xxxxxxxxxx 
DDMMMYYYY (xx) 
DDMMMYYYY (xx) 
No 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Yes 
xxxxxxxxxx 
xxxxxxxxxx 
DDMMMYYYY (xx) 
DDMMMYYYY (xx) 
Yes 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
Data taken from ‘On Treatment Surgery and Medical Procedures’ page. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.4-11 – On Treatment Blood Transfusions 
Full Analysis Set 
Cohort: Group 1 
 
 
Subject ID 
 
Age/ 
Gender 
 
Any blood 
transfusions 
Transfusion ID 
Date of Transfusion 
Category of Transfusion 
Units 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Yes 
xxxxxxxxxx 
DDMMMYYYY (xx) 
Platelet transfusion 
xx 
 
 
 
 
 
 
 
 
xx/M 
Yes 
xxxxxxxxxx 
DDMMMYYYY (xx) 
Plasma 
xx 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Data taken from ‘On Treatment Blood Transfusions’ page. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.4-12 – NGS Data 
Full Analysis Set 
Cohort: Group 1 
 
 
Subject ID 
 
Age/ 
Gender 
 
Gene / Codon / 
Amino acid change 
Vendor 
Date of Report 
Report Redacted 
Report Uploaded 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
BRAF /D594 / 
Alanine A 
STRATA 
DDMMMYYYY (xx) 
Yes 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
MEK1/MAP2K1 / 
K601 /Arginine R 
GUARDANT 
 
No 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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Version 5.0 25Jun2020 
 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.5-1 – Drug Administration 
Full Analysis Set 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
Treatment 
Administered? 
Dose (mg)  
Dose Date and Time (day) 
Dose Adjusted? / Reason 
 
 
 
 
 
 
xxx-xx 
xx/M 
Yes 
xxx 
DDMMMYYYY hh:mm (xx) 
Yes / Adverse event 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Yes 
xxx 
DDMMMYYYY hh:mm (xx) 
No 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Yes 
Xxx 
DDMMMYYYY hh:mm (xx) 
Yes / Other, xxxx 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                              Filename: (Specify file name.rtf) 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.5-2 – Dosing Interruptions and Changes 
Full Analysis Set 
 
Part A 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
 
Type of Change  
Start Date / End Date / 
Duration (days) 
If Adjustment, new 
dose amount (mg)  
Reason for 
Interruption/Adjustment 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
 
Interruption 
DDMMMYYYY / DDMMMYYYY / 
(xx) 
xxx   
Adverse Event  
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
 
Adjustment 
DDMMMYYYY / DDMMMYYYY / 
(xx) 
xxx  
Other, 
xxxxx 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                              Filename: (Specify file name.rtf) 
 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
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Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.5-3 – Drug Exposure 
Full Analysis Set 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
Number of 
cycles 
received [a] 
Duration of 
exposure  
(months) [b] 
 
 
Planned cumulative  
dose (mg) 
 
 
Actual cumulative  
dose received (mg)[c] 
 
 
 
Relative dose intensity [d] 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
xx 
xxx 
xxx (mg) 
xxx (mg) 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
xx 
xxx 
xxx (mg) 
xxx (mg) 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
[a] Number of cycles received = Number of cycles where the patient received at least one dose. 
[b] Duration of exposure (months) = (Date of last known treatment dosing with ulixertinib– date of initial dosing with ulixertinib) + 1 / 
30.4375. 
[c] Actual cumulative dose received (mg) = Sum of [(number of capsules dispensed – number of capsules returned) x 150]. 
[d] Relative dose intensity = 100 x Actual dose intensity / Planned dose intensity. Actual dose intensity (mg/day) is defined as Actual 
cumulative dose received (mg) / Duration of exposure (days). Planned dose intensity (mg/day) is defined as Planned cumulative dose (mg) / 
Duration of exposure (days). 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                              Filename: (Specify file name.rtf) 
  
 
 
 
 


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.5-3 – Study Drug Dispensed 
Full Analysis Set 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
Mg 
prescribed 
per dose 
Date 
Bottles 
Dispensed 
(day) 
Number of 
Bottles 
Dispensed 
Lot Number 
of the 
bottles 
dispensed 
Different Lot 
number 
dispensed to 
the patient? 
Lot number 
dispensed to 
patient /No of 
bottles 
Total 
Number of 
Capsules 
Dispensed 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
xxx 
DDMMMYYYY 
(xx) 
xx 
xxxx 
Yes 
xxxx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
xxx 
DDMMMYYYY 
(xx) 
xx 
xxxx 
No 
xxxx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                              Filename: (Specify file name.rtf) 
 
 


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.5-4 – Study Drug Returned 
Full Analysis Set 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
Cycle 
Reason 
capsules 
not 
returned 
Date 
Returned 
(day) 
Patient 
compliant 
since last 
visit? If 
no, reason 
Missed dose 
related to an 
adverse event? 
Number of 
Bottles Returned 
 
Lot Number 
of the 
bottles 
returned 
 
Total 
Number of 
Capsules 
Returned 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
2 
Lost 
DDMMMYYYY 
(xx) 
Yes 
Yes 
xx 
xxxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
3 
Other, xxxxx 
DDMMMYYYY 
(xx) 
No, xxxxx 
Yes 
xx 
xxxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                              Filename: (Specify file name.rtf) 
 
 


 
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Protocol: BVD-523-ABC 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X >)  
Data extraction date: DDMMMYYYY 
Listing 16.2.6-1 – Target Lesions 
Full Analysis Set 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
Visit 
Assessment 
Performed 
/ Reason 
Target 
Lesions at 
Screening? 
Lesion 
Number 
Tumor  
Type 
Organ 
Site 
Method 
Date of 
Scan 
(Day) 
Longest 
Diameter/ 
Short-
axis(mm) 
Sum of Longest 
Diameter (mm) / 
Change from 
baseline / % 
Change from 
baseline 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Screening 
Yes 
Yes 
T01 
Primary 
Bladder 
CT 
Scan 
DDMMMYYYY 
(xx) 
xxx  
xxx 
 
 
C2D1 
No, xxxx 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Screening 
Yes 
Yes 
T02 
Metastasis 
Other, 
xxxxx 
MRI 
DDMMMYYYY 
(xx) 
xxx  
xxx / xxx / xxx 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 
 
 


 
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Protocol: BVD-523-ABC 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.6-2 – Non-Target Lesions 
Full Analysis Set 
Group: Group 1 
Subject 
ID 
Age/ 
Gender 
Visit 
Assessment 
Performed / 
Reason 
Non-Target 
Lesions at  
screening 
Lesion Number 
Organ  
Site 
Method 
Date of Scan 
(Day) 
Result 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Screening 
Yes 
Yes 
NT01 
Bladder 
CT Scan 
DDMMMYYYY 
(xx) 
Present 
 
 
C2D1 
No, xxx 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Screening 
Yes 
Yes 
NT02 
Other,  
xxxx 
MRI  
DDMMMYYYY 
(xx) 
Absent 
(Disappeared) 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
Sort by group, subject ID, visit. 
 
 
 
 


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.6-3 – New Lesions 
Full Analysis Set 
Group: Group 1 
Subject 
ID 
Age/ 
Gender 
Visit 
Any New 
Lesions 
 
Lesion Number 
Method 
Date of Scan (Day) 
Organ Site 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
C2D29 
Yes 
NL01 
CT Scan 
DDMMMYYYY (xx) 
Abdomen  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
C2D29 
Yes 
NL02 
Other,  
xxxx 
DDMMMYYYY (xx) 
Bone 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                             Filename: (Specify file name.rtf) 
 
 
 
 


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.6-4 – Overall Response 
Full Analysis Set 
Group: Group 1 
Subject 
ID 
Age/ 
Gender 
Best Overall 
Response [a] 
Assessment 
Performed/ 
Reason 
Date of Assessment 
(Day) 
Target 
Lesion 
Response 
Non-Target 
Lesion 
Response 
New Lesions 
Overall 
Response 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
CR 
Yes 
DDMMMYYYY (xx) 
CR 
CR 
Yes 
CR 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
PD 
Yes 
DDMMMYYYY (xx) 
NE 
PD 
No 
NE, 
xxxx 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female, CR=Complete Response, Non CR/Non PD=Non Complete Response/Non Progressive Disease, PR=Partial Response, 
SD=Stable Disease, PD=Progressive Disease, NE=Not Evaluable. 
[a] Confirmed best overall response. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 
 
 


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.6-5 – Duration of Response (DOR) 
Full Analysis Set 
Group: Group 1 
Subject 
ID 
Age/ 
Gender 
Best Overall 
Response [a] 
Treatment  
Start Date 
Date of First 
Response 
Date of  
Last Tumor  
Assessment 
Date of Event / 
Censoring 
Event / 
Censoring Reason 
Duration of 
Response 
(months) 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
CR 
DDMMMYYYY 
DDMMMYYYY 
DDMMMYYYY 
DDMMMYYYY 
Death 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
PR 
DDMMMYYYY 
DDMMMYYYY 
DDMMMYYYY 
DDMMMYYYY 
Censored: xxxxx 
xx.x 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female, CR=Complete Response, PR=Partial Response, SD=Stable Disease, PD=Progressive Disease, NE=Not Evaluable. 
Event: progressive disease (PD) or death from any cause. 
This listing includes only patients with response (CR or PR). 
[a] Confirmed best overall response. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                              Filename: (Specify file name.rtf) 
 
 
 
 


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X  
Data extraction date: DDMMMYYYY 
Listing 16.2.6-6 – Progression-Free Survival (PFS) 
Full Analysis Set 
Group: Group 1 
Subject 
ID 
Age/ 
Gender 
Treatment  
Start Date 
Date of  
Last Tumor  
Assessment 
Date of Event/ 
Censoring 
Event / Censoring 
Reason 
PFS (months) 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
DDMMMYYYY 
DDMMMYYYY 
DDMMMYYYY 
Death 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
DDMMMYYYY 
DDMMMYYYY 
DDMMMYYYY 
Censored: xxxxx 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female, PFS=Progression-Free Survival. 
Event: progressive disease (PD) or death from any cause.  
The PFS (in months) is defined as the time from the first ulixertinib dose until the first radiographically documented progression 
of disease or death from any cause, whichever occurs first. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                            Filename: (Specify file name.rtf) 
 
 
 
 


 
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Protocol: BVD-523-ABC 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.6-7 – Survival Status 
Full Analysis Set 
Group: Group 1 
Subject 
ID 
Age/ 
Gender 
Completed 
End of 
Study? 
Any Anti-Cancer 
Treatment Since End 
of Study or Last 
FUP/ Start Date 
Any Tumor Assessment Since 
End of Study or Last FUP/ 
Assessment Date/ 
Overall Response 
 
Survival 
Status at 
Follow-Up 
Date of 
Death 
Last Known Date  
Patient Alive [a] 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Yes 
Yes/ DDMMMYYYY 
Yes/ DDMMMYYYY/ Complete 
Response 
 
Alive 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Yes 
No 
No 
 
Dead 
DDMMMYYYY 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female, FUP=Follow-up, CR=Complete Response, Non CR/Non PD=Non Complete Response/Non Progressive Disease, PR=Partial 
Response, SD=Stable Disease, PD=Progressive Disease, NE=Not Evaluable. 
[a] If Survival status at the time of follow-up is unknown. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 
 
 


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.7-1 – Adverse Events 
All Patients Set 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
ID 
 
Reported Term 
System Organ 
Class 
Preferred Term 
Start Date (day) 
End Date (day) 
TEAE? 
SAE? 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
xx 
xxxxxxxxx 
xxxxxxxxx 
xxxxxxxxx 
DDMMMYYYY (xx) 
DDMMMYYYY (xx) 
Yes 
Yes 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
xx 
xxxxxxxxx 
xxxxxxxxx 
xxxxxxxxx 
DDMMMYYYY (xx) 
DDMMMYYYY (xx) 
No 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female, TEAE=Treatment Emergent Adverse Event, SAE=Serious Adverse Event. 
ID as collected in the databased. 
MedDRA <vx.x>. NCI CTCAE v5.0. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                           Filename: (Specify file name.rtf) 
 
 


 
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Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.7-2 – Treatment-Emergent Adverse Events 
Safety Analysis Set 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
ID 
Reported Term 
/ System Organ 
Class 
/Preferred 
Term 
Start Date 
(Day) / End 
Date (Day) / 
Duration 
(days) 
SAE / 
Serious 
ness  
NCI- 
CTCAE 
Grade 
Relation 
Ship to 
Disease / 
Ulixertinib 
Action Taken 
with 
Ulixertinib 
Medication or 
Therapies? / 
Medication Name 
Outcome [a] 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
xx 
xxxxxxxx/ 
xxxxxxxxx/ 
xxxxxxxxx 
DDMMMYYYY 
(xx) / 
DDMMMYYYY 
(xx) / xx 
Yes / 
Hospital
ization 
1 
Related 
/Related 
Drug 
Interrupted 
Yes /xxxxxxxx, 
xxxxxxx  
 
 Res’d 
 
 
 
… 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
xx 
xxxxxxxx/ 
xxxxxxxxx/ 
xxxxxxxxx 
DDMMMYYYY 
(xx) / 
DDMMMYYYY 
(xx) / xx 
No 
3 
Possibly 
Related 
/Related 
Drug 
Interrupted 
Yes /xxxxxxxx  
 
Res’d seq, 
xxxxxx 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female, TEAE=Treatment Emergent Adverse Event, SAE=Serious Adverse Event. 
MedDRA <vx.x>. NCI CTCAE v5.0. 
ID as collected in the databased. 
[a] Res’d=Resolved, Res’d seq=Recovered/Resolved with sequelae, Ong=Ongoing, Unk=Unknown, Fatal=Fatal. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                           Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
Sort by group, subject ID, ascending Adverse Event Start Date and Reported Term. 
 
Outcome = “Res’d seq” please specify sequelae. 
 
 
 


 
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Listing 16.2.7-3 – Serious Adverse Events 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Listing 16.2.7-2 and include only AEs classified as Serious. 
 
 


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.7-4 – Deaths 
All Patients Set 
Group: Group 1 
Subject  
ID 
Age / 
Gender 
Date of Death (Day) 
Autopsy Performed? / 
Date of Autopsy 
Primary Cause of Death 
Treatment-Emergent Death 
[a] 
 
 
 
 
 
 
xxx-xx 
xx/M 
DDMMMYYYY (xx) 
No  
Progressive Disease 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
DDMMMYYYY (xx) 
Yes /DDMMMYYYY 
Adverse Event, xxxxxxx 
No 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
[a] A death is considered Treatment-Emergent if occurred after Ulixertinib administration. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
Specify primary cause of death if not PD.  
 
 


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.8-1 – Hematology 
Safety Analysis Set 
Group: Group 1 
Subject 
ID 
Age/ 
Gender 
Study 
Visit 
 
Sample Date and Time 
(Day) 
 
Laboratory 
Name 
Parameter 
(Unit) 
Result / 
Reference Range 
Indicator / CS?  
LLN – ULN 
CTC 
Grade 
Change from 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Screening  
 
DDMMMYYYY / hh:mm 
(xx) 
xxxxxxxx 
RBC (xxx) 
xx / L / CS 
 
xx – xx 
xx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
C1D1 
 
DDMMMYYYY / hh:mm 
(xx) 
xxxxxxxx 
RBC (xxx) 
xx / L / CS 
 
xx – xx 
xx 
xx 
 
 
… 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Screening 
 
DDMMMYYYY / hh:mm 
(xx) 
xxxxxxxx 
RBC (xxx) 
Not Done 
 
  
  
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
C1D1 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female, L=Low, H=High, ULN=Upper Limit of Normal, LLN=Lower Limit of Normal, CS=Clinically Significant, NCS=Non 
Clinically Significant. 
CTCAE v5.0. 
Baseline is the last available assessment prior to first dose of study treatment. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                              Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Sort by group, subject ID, ascending Sample Date and Time and Parameter. 
 
Include all hematology parameters. 
 
 


 
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Statistical Analysis Plan:  
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Listing 16.2.8-2 – Biochemistry 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Listing 16.2-8.1 for all biochemistry parameters. 
 
 
Listing 16.2.8-3 – Urinalysis 
Safety Analysis Set 
 
PROGRAMMING NOTES: 
 
Repeat Listing 16.2-8.1 for all urinalysis parameters. 
 
 


 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.8-4 – Pregnancy 
Safety Analysis Set 
Group: Group 1 
Subject  
ID 
Age / 
Gender 
Study  
Visit 
Sample  
Type 
Assessment  
Performed? /Reason 
Sample Date (Day) 
Result 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Screening 
Baseline 
Serum 
Yes 
DDMMMYYYY (xx) 
Positive 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Screening 
Serum 
No /xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
Baseline is the last available assessment prior to first dose of study treatment. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Sort by group, subject ID, visit. 
 
 
 
 
 


 
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Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
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Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.9-1 – Vital Signs 
Safety Analysis Set 
  
  Group: Group 1 
Subject 
ID 
Age / 
Gender 
Study  
Visit 
Assessment 
Performed? / 
Reason 
Assessment Date  
and Time (Day) 
Parameter  
(Unit) 
Result/ Reference Range 
Indicator / CS? [a] 
 
 
Position 
Change 
from 
baseline 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Screening 
Yes 
DDMMMYYYY hh:mm 
(xx) 
Systolic Blood 
Pressure (xxx)  
xx / H / CS 
 
Sitting 
 
 
 
 
 
 
… 
 
 
 
 
 
Baseline 
Yes 
DDMMMYYYY hh:mm 
(xx) 
Systolic Blood 
Pressure (xxx) 
xx / H / CS 
 
Supine 
 
 
 
… 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Screening 
No / xxxxxx 
 
 
Not Done 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female, L=Low, H=High, VH=Very High, ND=Not Done, CS=Clinically Significant, NCS=Non Clinically Significant. 
[a] If status = “Not Done” populate with “Not Done”. 
* Baseline is the last available assessment prior to first dose of study treatment. 
For temperature, Low if < 36.4°C; high if > 37.7°C. 
For pulse, Low if < 55bpm; high if 101-150bpm; very high if > 150bpm. 
For systolic blood pressure, Low if < 90mmHg; high if 131-160mmHg; very high if >= 161mmHg. 
For diastolic blood pressure, Low if < 60mmHg; high if 86-100mmHg; very high if >= 101mmHg. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                            Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
Sort by group, subject ID, ascending Assessment Date and Time and Parameter. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
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BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
 
Listing 16.2.9-2 – Electrocardiogram 
Safety Analysis Set 
Group: Group 1 
Subject  
ID 
Age / 
Gender 
Study  
Visit 
Assessment 
Performed? / 
Reason  
Assessment Date  
and Time  
Method/ 
Position 
Parameter 
(Unit) 
Result /CS? 
Change from 
baseline 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Screening 
Yes 
DDMMMYYYY hh:mm   
12 Lead 
Standard/ 
Supine 
Heart Rate 
(xxx) 
xx /No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Screening 
Yes 
DDMMMYYYY hh:mm  
12 Lead 
Standard/ 
Supine 
Heart Rate 
(xxx) 
xx /Yes 
 
 
 
 
 
 
  
  
 
 
Note: M=Male, F=Female, L=Low, H=High. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
Sort by group, subject ID, ascending Assessment Date and Time and Parameter. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
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Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.9-3 – ECHO/MUGA 
Safety Analysis Set 
Group: Group 1 
Subject  
ID 
Age / 
Gender 
Assessment  
Performed? / 
Reason 
Method 
Assessment Date (Day) 
Parameter (Unit) 
Result /CS? 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Yes 
Echocardiography 
DDMMMYYYY (xx) 
LVEF (xx) 
xx /No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
No /xxxx 
MUGA 
DDMMMYYYY (xx) 
LVEF (xx) 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female, LVEF=Left Ventricular Ejection Fraction. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                             Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
Sort by group, subject ID, ascending Assessment Date and Time. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 139 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.9-4 – Physical Examination 
Safety Analysis Set 
Part A 
Group: Group 1 
Subject  
ID 
Age /  
Gender 
 
Study  
Visit 
Assessment 
Performed? / 
Reason 
Assessment  
Date  
Region /Body 
System 
 
 
Result /CS? [a] 
 
Abnormal  
Findings  
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Screening 
Yes 
DDMMMYYYY  
HEENT 
Abnormal/ CS 
xxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Screening 
Yes 
DDMMMYYYY  
Thorax 
Not Done 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female, CS=Clinically Significant, NCS=Non Clinically Significant. 
[a] If status = “Not Done” populate with “Not Done”. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                             Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
Sort by group, subject ID, visit. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 140 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.9-5 – Ophthalmology Exam 
Safety Analysis Set 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
 
Study  
Visit 
Assessment 
Performed? / 
Reason 
Assessment 
Date  
Any Abnormal 
Clinically 
Significant Result? 
Examination Test 
Name 
 
 
Side 
 
 
Abnormal Finding 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Screening 
Yes 
DDMMMYYYY  
Yes 
Best-corrected 
visual acuity 
Left 
xxxxxxxxxxxx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Screening 
Yes 
DDMMMYYYY  
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female, CS=Clinically Significant, NCS=Non Clinically Significant. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                             Filename: (Specify file name.rtf) 
 
 
PROGRAMMING NOTES: 
 
Sort by group, subject ID, visit. 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 141 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y    
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X  
Data extraction date: DDMMMYYYY 
Listing 16.2.9-6 – Meals 
Safety Analysis Set 
Group: Group 1 
Subject  
ID 
Age /  
Gender 
Meal Consumed with 
Dose Administration? 
Meal Consumed 
Meal Date  
Meal Start Time 
Meal End Time 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
Yes 
Breakfast 
DDMMMYYYY  
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Yes 
Lunch 
DDMMMYYYY  
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                             Filename: (Specify file name.rtf) 
 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 142 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y  
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.9-7 – ECOG Performance Status 
Safety Analysis Set 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
Study  
Visit 
Assessment 
Performed? / 
Reason 
Date of Assessment (Day) 
ECOG Performance Status [a] 
 
 
 
 
 
 
xxx-xx 
xx/M 
Screening 
Yes 
DDMMMYYYY (xx) 
(0) Fully Active 
 
 
 
 
 
 
 
 
Baseline 
Yes 
DDMMMYYYY (xx) 
(0) Fully Active 
 
 
… 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/F 
Screening 
Yes 
DDMMMYYYY (xx) 
(1) Restricted 
 
 
 
 
 
 
 
 
Baseline 
No, xxxx 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
Baseline is the last available assessment prior to first dose of study treatment. 
[a] (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 self-care but unable to carry out any work activities 
    (3) Capable of only limited selfcare; confined 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) Death 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Sort by group, subject ID, visit, assessment date. 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 143 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y  
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.10-1 – Blood Pharmacodynamic Data 
Full Analysis Set 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
Study  
Visit 
Collection 
Date/Time (Day) / 
Timepoint 
Ulixertinib dose 
at the time of 
sample collection 
Patient at 
Steady 
state? 
Condition 
Specifics 
Parameter 
Result 
Comments 
 
 
 
 
 
 
 
 
 
 
xxx-xx 
xx/M 
C1D1 
ddmmmyyyy hh:mm 
(xx) / Pre-dose  
600mg BID 
Yes 
PMA (day 1, 
predose) 
% 
Inhibition 
simplified 
(0-100%) 
xxxx 
xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ddmmmyyyy hh:mm 
(xx) / 4-hours 
post dose 
450mg BID 
Yes 
 
PMA (day1, 
Cmax) 
% 
Inhibition 
simplified 
(0-100%) 
xxxxx 
xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROGRAMMING NOTES: 
 
Sort by group, subject ID, visit, assessment date and time 
 
 
 


 
Sponsor: BioMed Valley Discoveries 
Protocol: BVD-523-ABC 
Statistical Analysis Plan:  
2.0 / 09-Jun-2023 
 
Template Author: Andra Rusu 
Page 144 of 144 
BMSOP111/F2 
Version 5.0 25Jun2020 
 
 
 
 
BioMed Valley Discoveries                                                                                                Page 1 of Y  
Protocol: BVD-523-ABC (‘Delivery’ / ‘Type’) – Part X 
Data extraction date: DDMMMYYYY 
Listing 16.2.11-1 – Pharmacokinetic Data 
Full Analysis Set 
Group: Group 1 
Subject 
ID 
Age / 
Gender 
Study Visit 
Ulixertinib dose at 
the time of sample 
collection 
Patient at 
Steady state? 
Collection Date/Time 
(Day) / Timepoint 
Analyte 
Concentration (Unit) 
 
 
 
 
 
 
 
xxxx (ng/mL) 
xxx-xx 
xx/M 
C1D15 
600mg BID 
Yes 
ddmmmyyyy hh:mm (xx) 
/ Pre-dose  
BVD-523 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
450mg BID 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
Note: M=Male, F=Female. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM)                                               Filename: (Specify file name.rtf) 
 
PROGRAMMING NOTES: 
 
Sort by group, subject ID, visit, assessment date and time. 
 


Certificate Of Completion
Envelope Id: FC0A050EB8134327A4367C44E5822B5B
Status: Completed
Subject: Complete with DocuSign: BVD-523-ABC_SAP_2.0_09Jun2023-clean.docx, BVD-523-ABC_TFL_Shells_2.0-cl...
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David Sousa Manteigas
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Record Tracking
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             12-Jun-2023 | 17:53
Holder: David Sousa Manteigas
             dsousamanteigas@cmedresearch.com
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Cmed (Clinical Research Services) Limited
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Electronic Record and Signature Disclosure created on: 14-Jan-2021 | 10:03
Parties agreed to: Anna Groover, Brent Kreider, David Sousa Manteigas


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