A Phase I/II Open-Label Multicenter Study to Evaluate the Safety and Efficacy of AK-01 as Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumors
Phase: PHASE1
Conditions: Neoplasms, Neoplasm Metastasis, Triple Negative Breast Neoplasms, Head and Neck Neoplasms, Breast Neoplasms, Solid Tumor, Adult, Small Cell Lung Carcinoma
Sponsor: Eli Lilly and Company

J1O-MC-JZHA Protocol v.4 
 
Phase I/II Open-Label Multicenter Study to Evaluate the Safety and Efficacy of AK-01 as 
Monotherapy in Patients with Locally Advanced  or Metastatic Solid Tumors 
 
NCT03092934 
 
Approval Date: 10-APR-2018 

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PROTOCOL AURA-001 
 
 
 
A Phase I/II Open-Label Multicenter Study to Evaluate the Safety and Efficacy of AK-01 
as Monotherapy in Patients with Locally Advanced or Metastatic Solid Tumors 
 
 AK-01 (formerly known as LY3295668; erbumine) 
AurKa Pharma, Inc. 
1255 Robert-Bourassa Blvd, #1610 
Montreal, Quebec 
Canada H3B 3X3 
Version 
Date 
Version 1 
24/Jan/2017 
Version 2 
25/May/2017 
Version 3 
1/Jun/2017 
Version 4 
10/Apr/2018 
 
 
Confidential Information 
The information contained in this protocol is confidential and is intended for the 
use of clinical investigators. It is the property of AurKa Pharma, Inc. and should not 
be copied by or distributed to persons not involved in the clinical investigation of 
AK-01, unless such persons are bound by a confidentiality agreement with AurKa 
Pharma, Inc. 

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SYNOPSIS 
Title: 
A Phase I/II Open-Label Multicenter Study to Evaluate the Safety and Efficacy of AK-01 as 
Monotherapy in Patients with Locally Advanced or Metastatic Solid Tumors 
Phase of Development: 
Phase I/II 
Name of Investigational Medicinal Product: 
 AK-01 
Objectives: 
Phase I 
The primary objective is: 
• 
To determine the maximum tolerated dose (MTD) of AK-01 as monotherapy in patients with 
locally advanced or metastatic solid tumors. 
The secondary objective is: 
• 
To evaluate the tolerability and overall safety profile of AK-01. 
The exploratory objectives are: 
• 
To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of AK-01. 
• 
To compare PD markers of AK-01 target engagement in tumor biopsies. 
• 
To assess preliminary evidence of AK-01 anti-tumor activity. 
Phase II 
The primary objective is: 
• 
To evaluate the objective response rate (ORR) of AK-01 in up to 4 cohorts of locally advanced 
or metastatic solid tumor types of interest. 
The secondary objectives are: 
• 
To evaluate the tolerability and overall safety profile of AK-01. 
• 
To evaluate the PK and PD characteristics of AK-01. 
The exploratory objectives are: 
• 
To evaluate the effect of AK-01 on other clinical endpoints in these indications. 
• 
To evaluate the efficacy of AK-01 in patients with locally advanced or metastatic solid tumor 
types of interest with different molecular profiles. 

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Study Design: 
This open-label, non-randomized, multi-center study will explore the dose-limiting toxicities (DLTs), 
MTD, safety, PK, PD, and efficacy of AK-01 in patients with locally advanced or metastatic solid 
tumors. In the Phase I dose escalation part of this study, patients with solid tumors (excluding primary 
brain tumors) will receive AK-01 twice daily in cycles of 21 days in a multiple ascending dose (MAD) 
schedule in order to determine the MTD. Dose escalation will follow a 3 + 3 design. AK-01 target 
engagement will be explored in tumor biopsies. In the Phase II part of this study, AK-01 will be 
administered to patients in 2 cohorts of locally advanced or metastatic solid tumors of interest: small-
cell lung cancer (SCLC) and hormone positive/human epidermal growth factor receptor 2 
(HER2)-negative breast cancer (BC). Subsequently, at the sponsor’s discretion, patients with the 
following tumor types may be enrolled in up to 2 additional cohorts:  triple negative- breast cancer 
(TNBC), squamous cell cancers of the head neck (SCC-HN) and/or any other tumor type (OT) that 
warrants further exploration. Tumor response will be measured using Response Evaluation Criteria in 
Solid Tumors (RECIST) v.1.1. Dosing of AK-01 may continue until disease progression if the patient is 
receiving benefit and experiencing no severe toxicity in the opinion of the investigator. 
Patient Population: 
Patients with locally advanced or metastatic solid tumors will be enrolled in Phase I. In Phase II, 
initially patients with locally advanced or metastatic solid tumors of interest, such as  SCLC and BC will 
be enrolled. Subsequently, at the sponsor’s discretion, patients with TNBC, SCC-HN and/or one other 
solid tumor type. 
Number of Patients: 
In Phase I, up to 30 patients may be enrolled. In Phase II, up to 30 patients will be enrolled in each 
cohort, for a total of up to 120 patients.  
Main Eligibility Criteria: 
Male or female patients ≥18 years of age will be eligible if they meet the following criteria: 
• 
Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale. 
• 
Estimated life expectancy of ≥12 weeks. 
• 
Adequate organ function.  
• 
Have failed a minimum of 1 but no more than 4 regimens for locally advanced or metastatic 
disease. 
• 
Reliable and willing to make themselves available for the duration of the study, and willing to 
follow study procedures. 
• 
Locally advanced or metastatic solid tumors: 
• 
Phase I – All-comer evaluable tumors (excluding brain tumors). 
• 
Phase II – Tumors measurable by RECIST:  
1) SCLC having failed platinum-based therapy but be in a platinum sensitive relapse 
(having responded to up to 6 cycles of platinum therapy with at least SD, PR, or CR, and 
then maintained that response without progression for 3 months after the last platinum 
dose. Patients could have received maintenance therapy following the completion of 
platinum therapy. Patients who never responded or progresses < 3 months after the last 
platinum dose are not eligible);  

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2) estrogen receptor (ER+) and/or progesterone receptor (PR+) positive/HER2-negative BC 
having failed a hormone therapy and a CDK4/6 inhibitor.  Patients may have failed up to 2 
chemotherapy regimens and unlimited hormonal or other kinase therapies; 
3) relapsed/resistant TNBC;  
4) relapsed/refractory human papilloma virus (HPV) associated squamous cell cancers of 
the head and neck; and/or  
5) other tumor type that warrants further exploration. 
• 
No history of clinically significant cardiac disease. 
Study Treatment: 
In Phase II, AK-01 will be supplied as 25 mg capsules to be administered orally twice daily (BID) in 
cycles of 21 days. Patients will be encouraged to fast at least 1 hour before and following dosing. Dose 
reduction and/or interruption for any given patient will be permitted for toxicity throughout the 
study. 
Statistical Methods: 
Sample Size: In Phase I, the 3 + 3 design dose escalates cohorts of up to 9 patients in groups of a 
minimum of 3 until the MTD is identified: the dose immediately below the dose at which ≥2/3, ≥2/6, 
or ≥3/9 patients in a cohort experience a DLT during the first 21 days of treatment (Cycle 1). Up to 6 
additional patients may be dosed at or below the MTD to gain additional information for determining 
the phase II dose (P2D).  A sample size of up to 30 patients is considered sufficient to identify the MTD 
in Phase I; this is not powered on the basis of statistical hypothesis testing. In Phase II, up to 30 
patients for each tumor type will be administered study treatment. Whenever the true ORR is at 
least 20% for the study treatment, a sample size of 15 to 20 patients per tumor type provides 
approximately 60% power to reject the null hypothesis. 
PK: The primary PK parameters will be estimated using noncompartmental analysis, and will include 
the area under the AK-01 plasma concentration-time curve from time zero to 12 hours post-dose 
(AUC0-12) and to 24 hours post-dose (AUC0-24), the peak concentration (Cmax) and the time to Cmax (tmax). 
Other parameters such as apparent terminal elimination half-life (t1/2), apparent total plasma 
clearance (CL/F) and apparent volume of distribution (Vz/F) will also be calculated. PK parameters will 
be calculated individually and presented by summary statistics. 
PD and PK/PD: Changes in hematology measures (white blood cell count, neutrophil count, and 
lymphocyte count) will be explored; the relationship between hematological changes and AK-01 PK 
may be evaluated. Markers of dose-dependent target engagement (phospho-histone H3 and/or 
markers of apoptosis, phosphorylation, DNA damage, mitosis) will be evaluated, compared across 
time points, and compared between tumor biopsy samples. The inhibition of Aurora A kinase and 
Aurora B kinase by AK-01 may be compared. Additional PK and PD parameters may be calculated, and 
further PK/PD analyses may be conducted. 
Safety: Safety assessments will include clinical laboratory evaluations (hematology, clinical chemistry, 
endocrinology, and urinalysis), assessment of ECOG status, electrocardiogram, vital signs, pregnancy 
test(s), adverse event (AE) recording, and AE grading by National Cancer Institute Common 
Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE). Dose-limiting toxicities and the 
results of safety assessments will be summarized using descriptive statistics. The relationship between 
ECG parameters and AK-01 exposure may be explored. 
Efficacy: The primary assessment of efficacy in Phase II will be based on the ORR, which will be 
compared to 5% using a test of a single proportion.  RECIST v.1.1 criteria will be used to determine the 
effect of AK-01 on tumor burden. ORR, duration of objective response, best response on study, 

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progression-free survival, overall survival, and disease control rate may be summarized with 
descriptive statistics; additional efficacy parameters may be calculated.  
Molecular Profile: Molecular profiles predictive of tumor response to AK-01 may be explored in tumor 
tissue and blood (i.e., somatic mutations). Measures of efficacy may be compared in patients with 
different molecular tumor profiles.  
 

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TABLE OF CONTENTS 
SYNOPSIS ................................................................................................................................... 2 
TABLE OF CONTENTS................................................................................................................. 6 
LIST OF ABBREVIATIONS ......................................................................................................... 10 
1. INTRODUCTION ................................................................................................................... 14 
1.1. General Introduction ..................................................................................................... 14 
1.2. Rationale and Justification for the Study ...................................................................... 14 
1.3. Data from Ongoing Phase I Part of the Study ............................................................... 15 
2. STUDY OBJECTIVES .............................................................................................................. 16 
2.1. Phase I ............................................................................................................................ 16 
2.2. Phase II ........................................................................................................................... 16 
3. INVESTIGATIONAL PLAN ..................................................................................................... 17 
3.1. Overall Study Design and Plan – Phase I ....................................................................... 18 
3.1.1. Dose-Limiting Toxicity .............................................................................................. 18 
3.1.2. Maximum Tolerated Dose ........................................................................................ 18 
3.1.3. Dose Escalation Rules ............................................................................................... 19 
3.1.4. Intrapatient Dose Adjustments ................................................................................ 20 
3.2. Overall Study Design and Plan – Phase II ...................................................................... 21 
3.3. Toxicity Management .................................................................................................... 21 
3.3.1. Potential AEs ............................................................................................................ 21 
3.3.2. Dose Modifications for Toxicity ............................................................................... 22 
3.4. Discussion of Design and Control .................................................................................. 24 
3.5. Estimated Duration of the Study ................................................................................... 24 
3.6. Determination of Sample Size ....................................................................................... 24 
3.7. Study Completion .......................................................................................................... 25 
3.8. End of Trial ..................................................................................................................... 25 
4. STUDY POPULATION ........................................................................................................... 26 
4.1. Criteria for Enrollment ................................................................................................... 26 
4.1.1. Inclusion Criteria ...................................................................................................... 26 
4.1.2. Exclusion Criteria ...................................................................................................... 28 
4.2. Discontinuation ............................................................................................................. 29 
4.2.1. Discontinuation of Patients ...................................................................................... 29 
4.2.2. Discontinuation of Study Centers ............................................................................ 30 
4.2.3. Discontinuation of the Study ................................................................................... 30 
5. TREATMENT ........................................................................................................................ 31 

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5.1. Rationale for Selection of Dose ..................................................................................... 31 
5.2. Investigational Medicinal Product ................................................................................. 31 
5.2.1. Investigational Medicinal Product Administration .................................................. 32 
5.2.2. Dose and Regimen ................................................................................................... 32 
5.3. Method of Assignment to Treatment ........................................................................... 33 
5.3.1. Special Treatment Considerations ........................................................................... 33 
5.3.2. Evaluable Patients .................................................................................................... 33 
5.4. Specific Restrictions/Requirements .............................................................................. 33 
5.5. Blinding .......................................................................................................................... 33 
5.6. Concomitant Therapy .................................................................................................... 34 
6. PHARMACOKINETIC, PHARMACODYNAMIC, SAFETY AND EFFICACY DATA COLLECTION .. 35 
6.1. Pharmacokinetic Evaluations ........................................................................................ 35 
6.1.1. Samples for Pharmacokinetic Evaluations ............................................................... 35 
6.1.2. Bioassay .................................................................................................................... 35 
6.2. Pharmacodynamic Evaluations ..................................................................................... 35 
6.2.1. Samples for Pharmacodynamic Evaluations ............................................................ 35 
6.2.2. Evaluation of Target Engagement ............................................................................ 36 
6.3. Molecular Profile Evaluation ......................................................................................... 36 
6.3.1. Samples for Molecular Profile Evaluations .............................................................. 36 
6.3.2. Evaluation of Molecular Profile ............................................................................... 36 
6.4. Storage of Samples ........................................................................................................ 36 
6.5. Safety Evaluations ......................................................................................................... 37 
6.5.1. Safety Measures ....................................................................................................... 37 
6.5.2. Safety Data Collection and Review .......................................................................... 37 
6.5.3. Adverse Events ......................................................................................................... 38 
6.5.4. Serious Adverse Events ............................................................................................ 39 
6.5.5. Safety Assessment Committee ................................................................................ 40 
6.6. Product Complaint Handling ......................................................................................... 40 
6.7. Efficacy Evaluations ....................................................................................................... 41 
6.7.1. Radiographic Tumor Assessment ............................................................................. 41 
6.7.2. Overall Survival......................................................................................................... 41 
7. DATA MANAGEMENT METHODS ........................................................................................ 42 
7.1. Data Quality Assurance ................................................................................................. 42 
7.2. Direct Data Entry and Computerized Systems .............................................................. 42 
7.3. Record Retention ........................................................................................................... 43 
8. PHARMACOKINETIC, PHARMACODYNAMIC, SAFETY, AND EFFICACY DATA ANALYSES ..... 44 

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8.1. Data Analysis Plans ........................................................................................................ 44 
8.1.1. General Considerations ............................................................................................ 44 
8.1.2. Study Participants .................................................................................................... 44 
8.1.3. Pharmacokinetic and Pharmacodynamic Analyses ................................................. 44 
8.1.4. Safety Analysis .......................................................................................................... 45 
8.1.5. Treatment Compliance............................................................................................. 45 
8.1.6. Efficacy Analysis ....................................................................................................... 46 
8.1.7. Molecular Profile Analysis ........................................................................................ 46 
8.2. Missing Data .................................................................................................................. 46 
8.3. Interim Data Analysis ..................................................................................................... 46 
9. INFORMED CONSENT, ETHICAL REVIEW, AND REGULATORY CONSIDERATIONS............... 47 
9.1. Informed Consent .......................................................................................................... 47 
9.2. Ethical Review ................................................................................................................ 47 
9.3. Regulatory Considerations ............................................................................................ 47 
9.4. Protocol Compliance ..................................................................................................... 47 
9.5. Confidentiality of Patient Information .......................................................................... 48 
9.6. Protocol Signatures ....................................................................................................... 48 
9.7. Final Report Signature ................................................................................................... 48 
10. PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT ........................................................ 49 
REFERENCES ............................................................................................................................ 50 
APPENDICES ............................................................................................................................ 51 
 

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List of Tables 
Table 1. AK-01 Dose Modifications for Toxicity ...................................................................... 22 
Table 2. Statistical Power of Observed Overall Response Rates ............................................ 25 
Table 3. AK-01 Dosing ............................................................................................................. 32 
Table 4. CTCAE Guidelines for Evaluation of AE Severity ....................................................... 39 
Table 5. Evaluation of Overall Tumor Response by RECIST version 1.1 ................................. 68 
List of Figures 
Figure 1. Overview of Study Design ........................................................................................ 17 
Figure 2. Dose Escalation Rules .............................................................................................. 20 
List of Appendices 
Appendix 1. Schedule of Events (Phase II) .............................................................................. 52 
Appendix 2. Clinical Laboratory Tests ..................................................................................... 56 
Appendix 3. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation10 ...... 57 
Appendix 4. Eastern Cooperative Oncology Group (ECOG) Performance Status11 ................ 58 
Appendix 5. New York Heart Association Functional Classification12 .................................... 59 
Appendix 6. Medications Known to Cause Prolongation of the QT Interval or Torsades de 
Pointes7 .................................................................................................................. 60 
Appendix 7. Fridericia Formula for Correction of the QT Interval7 ........................................ 62 
Appendix 8. Eligible Breast Cancer Biomarker Expression ..................................................... 63 
Appendix 9. Common Terminology Criteria for Adverse Events, v. 4.03 ............................... 64 
Appendix 10. Response Evaluation Criteria in Solid Tumors, v. 1.19 ...................................... 65 
Appendix 11. Contacts ............................................................................................................ 69 
Appendix 12. Summary of Protocol Changes ......................................................................... 70 
 

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LIST OF ABBREVIATIONS 
AE 
Adverse event 
AUC 
Area under the plasma concentration-time curve 
AUC0-12 
AUC from time zero to 12 hours post-dose 
AUC0-24 
AUC from time zero to 24 hours post-dose 
AurA 
Aurora A kinase 
AurB 
Aurora B kinase 
ANC 
Absolute neutrophil count 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
ATP 
Adenosine triphosphate 
BC 
Breast cancer 
BID 
Twice a day 
C 
Cycle 
CDK1 
Cyclin-dependent kinase 1 
CDK4/6 
Cyclin-dependent kinase 4/6 
CL/F 
Apparent total plasma clearance after extravascular administration 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
Cmax 
Maximum observed plasma concentration  
CNS 
Central nervous system 
eCRF 
Electronic case report form 
CT 
Computed tomography  
CTCAE 
Common Terminology Criteria for Adverse Events 

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D 
Day 
DLT 
Dose-limiting toxicity 
DNA 
Deoxyribonucleic acid 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EDC 
Electronic data capture 
eGFR 
Estimated glomerular filtration rate 
ER+ 
Estrogen receptor positive 
ELISA 
Enzyme-linked immunosorbent assay 
FSH 
Follicle stimulating hormone 
GCP 
Good Clinical Practices 
G-CSF 
Granulocyte-colony stimulating factor 
GI 
Gastrointestinal 
HIV 
Human immunodeficiency virus 
HER 
Human epidermal growth factor receptor 2  
HNSTD 
Highest non-severely toxic dose 
hr 
Hour 
ICD 
Informed consent documents 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IMP 
Investigational medicinal product 
IRB 
Institutional Review Board 
MAD 
Multiple ascending dose 

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mg 
Milligram 
min 
Minute 
mL 
Milliliter 
MRI 
Magnetic resonance imaging 
msec 
Millisecond 
MTD 
Maximum tolerated dose 
NCI 
National Cancer Institute 
ORR 
Objective response rate 
OS 
Overall survival 
PD 
Pharmacodynamic 
PFS 
Progression-free survival 
PK 
Pharmacokinetic 
PR+ 
Progesterone receptor positive 
PTEN 
Phosphatase and tensin homolog 
QTcF 
QT interval corrected for heart rate using the Fridericia formula 
Rb1 
Retinoblastoma protein 1 
RECIST 
Response Evaluation Criteria in Solid Tumors 
P2D 
Phase II dose 
SAC 
Safety Assessment Committee 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SCLC 
Small-cell lung cancer 
TP53 
Tumor protein p53 

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tmax 
Time of maximum observed concentration 
t1/2 
Apparent terminal elimination half-life 
TdP 
Torsades de Pointes 
ULN 
Upper limit of normal 
Vz/F 
Apparent volume of distribution during the terminal elimination phase 

A U R A -0 0 1  
1 0/ A pr/ 2 0 1 8  
Cli nic al St u d y Pr ot oc ol  
V ersi o n 4   
 
 
A ur K a P h ar m a, I nc. — C o nfi d e nti al  
P a g e 1 4  of 9 9  
 
1.  I N T R O D U C TI O N 
1. 1.  G e n er al I ntr o d ucti o n  
T h e A ur or a ki n as es c o m pris e a f a mil y of s eri n e/t hr e o ni n e ki n as es t h at pl ay a critic al r ol e i n t h e 
mit otic pr oc ess .1 A ur or a A ki n as e  (A ur A ) l oc aliz es t o t h e c e ntr os o m es a n d s pi n dl e p ol es a n d 
r ecr uits t h e cycli n B 1– C D K 1 c o m pl ex, c o m mitti n g t h e c ell t o mit osis. 1 A ur or a B ki n as e (A ur B ) 
pl a ys a  r ol e i n c hr o m os o m e c o n d e ns ati o n, r e g ul ati o n of ki n et oc h or e f u ncti o n, a n d cyt o ki n esis. 
A m plific ati o n of t h e A ur A  g e n e A U R K A  is o nc o g e nic, a n d h as b e e n o bs er v e d i n c ol or ect al, 
g astric, pr ost at e, a n d br e ast  c a nc ers; t h e A U R K A  P h e 3 1Il e p ol y m or p his m is ass oci at e d wit h a n 
i ncr e as e d ris k f or es o p h a g e al, o v ari a n, l u n g, a n d br e ast c a nc ers.2 A ur A  o v er ex pr essi o n m a y als o 
pl a y a r ol e i n r esist a nc e t o p aclit ax el, g efiti ni b, a n d cis pl ati n. 3- 5  
Disr u pti o n of A ur A acti vit y si g nific a ntl y i m p airs mit otic pr o gr essi o n t hr o u g h acti v ati o n of t h e 
mit otic c h ec k p oi nt .2 T his r es ults i n d ef ects i n mit otic s pi n dl e f or m ati o n a n d pr o m et a p h as e 
arr est, wit h s u bs e q u e nt c ell d e at h t hr o u g h pr o a p o pt otic p at h w a ys.2 I n c o ntr ast, A ur B i n hi biti o n 
c a us es t h e c ell t o b y p ass t h e mit otic c h ec k p oi nt, cr e ati n g p ol y pl oi d c ells t hr o u g h f ail ur e of  
cyt o ki n esis.6 D u al A ur A/ B or A ur B -d o mi n a nt ki n as e i n hi bit ors all o w c ells t o b y p ass t h e mit otic 
c h eck p oi nt , wit h a ntit u m or acti vit y b ei n g d e p e n d e nt o n acti v ati o n of a p o pt osis i n r es p o ns e t o 
i ncr e asi n g g e n o mic i nst a bilit y.6 T his A ur B p h e n oty p e will d o mi n at e t h e A ur A p h e n ot y p e if 
i n hi bit ors ar e n ot hi g hl y s el ecti v e f or A ur A. 
A K -0 1 is a r e v ersi bl e , A T P -c o m p etiti v e s m all m ol ec ul e dr u g t h at i n hi bits A ur A wit h 1 0 0 0-f ol d 
s el ecti vit y o v er A ur B i n b ot h bi oc h e mic al a n d c ell-b as e d ass a ys.  A d mi nistr ati o n of A K --0 1 t o 
mic e i m pl a nt e d wit h p ati e nt -d eri v e d x e n o gr afts r es ults i n t u m or gr o wt h arr est or r e gr essi o n i n 
a n u m b er of t u m or t y p es.  I n vitr o a n d i n viv o d at a s u g g ests t u m ors wit h R b 1 l oss-of -f u ncti o n 
m ut ati o ns  m a y b e p artic ul arl y r es p o nsi v e t o i n hi biti o n of A ur A  (s e e I n v esti g at or’s Br oc h ur e). 
 
 
F urt h er i nf or m ati o n o n t h e k n o w n b e n efits a n d ris ks of A K -0 1 c a n b e f o u n d i n t h e I n v esti g at or’s 
Br oc h ur e.   
1. 2.  R ati o n al e a n d J ustific ati o n f or t h e St u d y  
P r ecli nic al d at a d e m o nstr ati n g bi ol o gic acti vit y i n viv o wit h a n acc e pt a bl e s af et y pr ofil e 
s u p p orts t h e e v al u ati o n of A K-0 1 i n h u m a ns.  
T h e s el ecti vit y of A K -0 1 f or A ur A diff er e nti at e s A K-0 1  fr o m ot h er i n hi bit ors of  A ur or a ki n as es  
( e. g., ML N 8 2 3 7 , A Z D 1 1 5 2, a n d P H A-7 3 9 3 5 8 ),1 a n d m a y all o w A K -0 1 t o elicit t h e b e n efits of 
A ur A i n hi biti o n wit h o ut tri g g eri n g t h e a d v ers e a n d oft e n d os e -li miti n g n e utr o p e ni a ass oci at e d 
wit h A ur B i n hi biti o n.   
T h e pr es e nt st u d y will e v al u at e  th e s af et y a n d effic acy of A K -0 1  i n p ati e nts wit h l oc all y 
a d v a nc e d or m et ast atic s oli d t u m ors, wit h a n e m p h asis o n s m all-c ell l u n g c a nc er ( S CL C), 
C CI

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estrogen receptor (ER+) and/or progesterone receptor (PR+) positive/human epidermal growth 
factor receptor 2 (HER2)-negative  breast cancer (BC), triplenegative- breast cancer (TNBC), 
human papilloma virus (HPV) associated squamous cell cancers of the head neck (SCC-HN), and 
any other tumor type (OT) that warrants further exploration.  A large proportion of these 
patients bear a Rb1 loss-of function mutation, a molecular signature which sensitized animal 
models to AK-01 in preclinical testing (see Investigator’s Brochure). Patients are eligible for the 
Phase II part of this study if they have failed standard of care therapies which do not preclude 
therapy with an AurA inhibitor: hormone therapy and CDK4/6 inhibitor for ER+ and/or 
PR+/HER2-negative BC, platinum-based therapy for SCLC, relapsed/resistant TNBC, HPV 
associated SCC-HN, and/or any other tumor type that warrants further exploration (see 
Investigator’s Brochure for further details). 
1.3. Data from Ongoing Phase I Part of the Study 
A total of 12 patients have been dosed in the ongoing Phase I part of the study since June 2017 
with doses of AK01 of up to 75 mg BID. Dose- limiting- toxicities (DLTs) were noted at both 
75 mg and 50 mg dose levels. The 25 mg twice a day (BID) dose has been chosen as the dose for 
Phase II.   
Based on safety analysis of the ongoing Phase I part of the study, the following are considered 
as potential adverse events (AEs): bone marrow toxicity including neutropenia and 
thrombocytopenia; gastrointestinal toxicity including mucositis and diarrhea; and corneal 
deposition with blurry vision and double vision.  Appropriate follow up and rapid therapy for 
any of these events will be undertaken.  
Additional information on the reported AEs is available in the investigator’s brochure (IB). 

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2. STUDY OBJECTIVES 
2.1. Phase I 
The primary objective is:  
• 
To determine the maximum tolerated dose (MTD) of AK-01 as monotherapy in patients 
with locally advanced or metastatic solid tumors. 
The secondary objective is: 
• 
To evaluate the tolerability and overall safety profile of AK-01. 
The exploratory objectives are: 
• 
To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of 
AK-01. 
• 
To compare PD markers of AK-01 target engagement in tumor biopsies. 
• 
To assess preliminary evidence of AK-01 anti-tumor activity.  
2.2. Phase II 
The primary objective is: 
• 
To evaluate the objective response rate (ORR) of AK-01 in up to 4 cohorts of locally 
advanced or metastatic solid tumor types of interest. 
The secondary objectives are: 
• 
To evaluate the tolerability and overall safety profile of AK-01. 
• 
To evaluate the PK and PD characteristics of AK-01. 
The exploratory objectives are: 
• 
To evaluate the effect of AK-01 on other clinical endpoints in these indications.  
• 
To evaluate the efficacy of AK-01 in patients with locally advanced or metastatic solid 
tumor types of interest with different molecular profiles. 

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3. INVESTIGATIONAL PLAN 
This open-label, non-randomized, multi-center study will explore the safety, PK, PD, and 
efficacy of AK-01 administered in 21-day cycles to patients with locally advanced or metastatic 
solid tumors.  
In Phase I of this study, patients with locally advanced or metastatic solid tumors (all-comers) 
will be administered AK-01 according to a multiple ascending dose (MAD) schedule to 
determine the MTD.  The phase II dose (P2D) may be confirmed in up to 6 additional patients, 
and may take into consideration the MTD, evidence of AurA and AurB target engagement, and 
PK.  The P2D will not exceed the MTD. Throughout Phase I, safety, tolerability, PK, PD, and early 
evidence of anti-tumor activity will be assessed.  
In Phase II of this study, AK-01 will be administered in up to 4 cohorts; initially in patients with 
SCLC and BC, and subsequently, at the sponsor’s discretion, in patients with one of the 
following: TNBC, HPV associated SCC-HN, and/or any OT that warrants further exploration.  
Efficacy, safety, PK, and PD will be assessed.   
An overview of the study design is given in Figure 1. 
Figure 1. Overview of Study Design 
 

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3.1. Overall Study Design and Plan – Phase I 
In Phase I, approximately 30 patients with locally advanced or metastatic tumors for whom no 
treatment of higher priority exists will be enrolled. The 3 + 3 method will be used for increasing, 
maintaining, or decreasing the dose of AK-01. 
The following rules and definitions will guide dose escalation. 
3.1.1. Dose-Limiting Toxicity 
A DLT is any AE during Cycle 1 which is considered by the investigator(s) to be related (possibly 
or probably) to the IMP, and fulfills at least one of the following criteria using version 4.03 of 
the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI CTCAE, 
see Appendix 9): 
• ≥Grade 3 non-hematological toxicity, except for alopecia. Nausea, vomiting, and 
diarrhea will NOT be considered DLT unless they have been fully medically managed by 
institutional guidelines and yet remain ≥Grade 3 for >3 days. 
• Febrile neutropenia of any grade. 
• Grade 3 neutropenia or thrombocytopenia lasting >5 days. 
• Grade 4 neutropenia or thrombocytopenia. 
• ≥5 times upper limits of normal (ULN) aspartate aminotransferase (AST) or alanine 
aminotransferase (ALT) with >2 times ULN bilirubin. If the liver has tumor involvement, 
AST and ALT ≥7 times ULN with >2 times ULN bilirubin will be considered a DLT. In 
addition, any patient with this degree of hepatic effect will be withdrawn from the 
study. 
• ≥Grade 4 prolongation of QT interval corrected using the Fridericia formula (QTcF, see 
Appendix 7) on 2 separate ECG readings approximately 5 min apart. 
Patients who exhibit a DLT will require interruption of IMP, and may be discontinued from 
further participation in the study. Dose modifications for toxicity are described in Section 3.3.2. 
Patients experiencing a DLT will be medically managed by the investigator in consultation with 
the sponsor.  
See Section 5.3.2 for guidelines on patient replacement. 
DLTs will be evaluated for each cohort from the time of first administration of AK-01 through 
the first 21-day cycle. The frequency of DLTs in the previous cohort will determine whether the 
dose of the subsequent cohort will increase, decrease, be maintained, or stop. 
3.1.2. Maximum Tolerated Dose 
The MTD is the dose immediately below the dose at which ≥2/3, ≥2/6, or ≥3/9 patients in a 
cohort experience a DLT during the first 21 days of treatment (Cycle 1).  

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3.1.3. Dose Escalation Rules 
The starting dose for the first cohort will be 25 mg BID AK-01, administered orally for 21 days. 
Each cohort will initially enroll up to 3 patients, and may be expanded up to 9 patients based on 
the dose escalation rules.  At least 3 patients must complete Cycle 1 or experience a DLT before 
any dose escalation decision may be made. In the first cohort only, one patient will initially be 
dosed alone; if no DLT is experienced within 24 hours of the first dose, the remaining patients in 
the cohort may be dosed. Starting in cohort 2, patients may be dosed concurrently.  
Dose escalation will be guided by the following rules (depicted graphically in Figure 2):  
• If none of the 3 patients in a cohort experience a DLT during Cycle 1, the dose may be 
escalated for the subsequent cohort. If ≥2 patients out of 3 experience a DLT during 
Cycle 1, the MTD has been exceeded and no additional patients will be enrolled at that 
dose level. If 1 patient out of 3 experiences a DLT during Cycle 1, the cohort will be 
expanded with an additional 3 patients.  
• If ≥1 DLT is observed in the additional 3 patients (≥2/6), the MTD has been exceeded 
and no additional patients will be enrolled at that dose level. If no DLT is observed in the 
additional 3 patients (1/6), the dose may be escalated for the subsequent cohort. 
Alternatively, if no DLT is observed in the additional 3 patients (1/6) but further 
assessment of toxicity at the dose level is warranted, the sponsor (in conjunction with 
the investigator) may decide to enroll an additional 3 patients at that dose level. 
• If ≥2 DLT are observed in the additional 3 patients (≥3/9), the MTD has been 
exceeded. If ≤1 DLT is observed in the additional 3 patients (≤2/9), the dose may 
be escalated for the subsequent cohort. 
A schematic for the dose escalation rules for any dose level in this study is presented in Figure 
2.  

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Figure 2. Dose Escalation Rules 
Enrollment cannot begin in a new cohort until the Safety Assessment Committee (SAC, see 
Section 6.5.5) has met to discuss the data from the previous dose level. Safety data will be the 
primary criteria for both the decision to dose escalate and for selecting the dose to be 
administered in the next cohort. The 25 mg BID dose has been chosen as the dose for Phase II 
(Section 1.3). A separate document detailing the plan for communicating decisions between 
the sponsor, SAC, and study sites will be provided to investigators (e.g., for dose-escalation 
decisions, management of DLTs, study-related modifications, etc.). 
3.1.4. Intrapatient Dose Adjustments 
Dose modifications for toxicity are described in Section 3.3.2. 
Following Cycle 1, if no DLT-equivalent toxicity is experienced, a given patient’s dose may be 
maintained or escalated (provided the dose does not exceed the MTD). The decision to dose 
escalate a patient after Cycle 1 will be recommended by the investigator and discussed with the 
sponsor’s medical representative. A patient can only be escalated to a dose level at which a 
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A U R A -0 0 1  
1 0/ A pr/ 2 0 1 8  
Cli nic al St u d y Pr ot oc ol  
V ersi o n 4   
 
 
A ur K a P h ar m a, I nc. — C o nfi d e nti al  
P a g e 2 1  of 9 9  
 
mi ni m u m of  3 p ati e nts h a v e c o m pl et e d Cycl e 1 a n d w hic h h as b e e n d e e m e d acc e pt a bl e  b y  t h e 
S A C . I ntr a p ati e nt A K -0 1  d os e esc al ati o n m a y occ ur f oll o wi n g c o m pl eti o n of t h e p ati e nt’s c urr e nt 
cycl e. 
A n y p ati e nt w h o c onti n u e s i n t h e st u d y f oll o wi n g Cycl e 1 will b e ass ess e d f or t oxicit y a n d 
t ol er a bilit y t hr o u g h o ut t h eir p artici p ati o n. T h e s af et y a n d t ol er a bilit y of d os e esc al ati o n i n t h es e 
p ati e nts m a y g ui d e d os e d ecisi o ns f or n e w c o h orts.  
F oll o wi n g c o m pl eti o n of Cycl e 1, d osi n g  m a y c o nti n u e i n 2 1 -d a y cycl es  u ntil dis e as e pr o gr essi o n 
if t h e p ati e nt is r ec ei vi n g b e n efit a n d is ex p eri e nci n g n o s e v er e t oxicit y i n t h e o pi ni o n of t h e 
i n v esti g at or.  
3. 2.  O v er all St u d y D esi g n a n d Pl a n – P h as e II  
P h as e II will e v al u at e  t h e pr eli mi n ar y effic acy  of A K -0 1 i n u p t o 4 c o h orts; i niti all y i n p ati e nts 
wit h l oc all y a d v a nc e d or m et ast atic S CL C a n d B C, a n d s u bs e q u e ntl y, at s p o ns or’s discr eti o n, i n 
p ati e nts wit h T N B C , S C C -H N , a n d O T . U p t o 3 0 p ati e nt s m a y  b e e nr oll e d i n e ac h c o h ort, gi vi n g 
a n esti m at e d  t ot al of u p t o 1 2 0  p ati e nts .  Si nc e A K -0 1 is a n ex p eri m e nt al tr e at m e nt, p ati e nts 
will n e e d t o h a v e f ail e d st a n d ar d of c ar e t h er a pi es  (i. e., pl ati n u m -b as e d t h er a p y  f or S CL C; 
h or m o n e t h er a p y a n d a C D K 4/ 6 i n hi bit or f or B C; r el a ps e d/r esist a nt T N B C p ati e nts; st a n d ar d 
t h er a p y f or H P V ass oci at e d S C C -H N ) b ef or e b ei n g e nr oll e d i n t his tri al.  
All o p e n c o h orts i n P h as e II  m a y b e gi n e nr oll m e nt c o nc urr e ntl y  a n d w ill b e d os e d at 2 5  m g BI D .  
D os e i ncr e as es will n ot b e all o w e d i n P h as e II.  D os e m o dific ati o ns f or t oxicit y  ar e d escri b e d i n 
S ecti o n 3. 3. 2 .  
Aft er Cycl e 1, d osi n g of A K -0 1 m a y  c o nti n u e i n 2 1-d a y cycl es u ntil  dis e as e pr o gr essi o n if t h e 
p ati e nt is r ec ei vi n g b e n efit , a n d is ex p eri e nci n g n o s e v er e t oxicit y i n t h e o pi ni o n of t h e 
i n v esti g at or. 
 
3. 3.  T o xicit y M a n a g e m e nt  
3. 3. 1.  P ot e nti al A Es  
B a s e d o n s af et y d at a  of t h e o n g oi n g P h as e I p art of t h e st u d y, t h e f oll o wi n g ar e c o nsi d er e d as 
p ot e nti al A Es: b o n e m arr o w t oxicit y i ncl u di n g n e utr o p e ni a a n d t hr o m b ocyt o p e ni a; 
g astr oi nt esti n al t oxicit y i ncl u di n g m uc ositis a n d di arr h e a; a n d c or n e al d e p ositi o n wit h bl urr y 
visi o n a n d d o u bl e visi o n.  A p pr o pri at e f oll o w u p a n d r a pi d t h er a p y f or a n y of t h es e e v e nts 
s h o ul d b e u n d ert a k e n 
 
  
B o n e m arr o w h y p oc ell ul arit y w as o bs er v e d  i n r ats a n d d o gs, wit h d ecr e as e d  h e m at ol o gic 
c orr el at es. P ati e nts will b e m o nit or e d f or b o n e m arr o w t oxicit y wit h fr e q u e nt bl o o d c o u nts, a n d 
s h o ul d b e s u p p ort e d wit h bl o o d pr o d uct tr a nsf usi o n a n d h e m at o p oi etic gr o wt h f act ors as 
C CI

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d escri b e d i n S ecti o n 5. 6 . P ati e nts s h o ul d b e m o nit or e d f or f e v er a n d p ossi bl e n e utr o p e nic f e v er, 
a n d tr e at e d a p pr o pri at ely wit h br o a d s p ectr u m a nti bi otics as p er i nstit uti o n al g ui d eli n es.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3. 3. 2.  D os e M o dific ati o ns f or T oxicit y  
D os e m o dific ati o ns ar e p er mitt e d as d escri b e d b el o w f or t oxiciti es t h at e m er g e t hr o u g h o ut t h e 
st u d y. 
I M P ma y b e wit h h el d f or u p t o 2 1 d a ys t o all o w s uffici e nt ti m e f or r ec o v ery fr o m t oxicit y, b ut 
p ati e nts w h o d o n ot r ec ov er wit hi n t his p eri o d will b e wit h dr a w n . F oll o wi n g r ec o v er y, I M P m a y 
b e r es u m e d at t h e s a m e d os e or at a r e d uc e d d osi n g fr e q u e ncy , d e p e n di n g o n t h e t y p e a n d 
s e v erit y of t oxicit y ex p eri e nc e d (s e e T a bl e 1 ).  
T a bl e 1  d escri b e s A K -0 1 d os e m o dific ati o n s f or p ati e nts w h o ex p eri e nc e t oxicit y . 
T a bl e 1 . A K-0 1  D os e M o dific ati o n s f or T o xicit y 
T o xicit y  
D os e M o dific ati o n  
Q T c F Pr ol o n g ati o n  
 
˂ Gr a d e 2  
C o nti n u e at c urr e nt d os e l e v el.  
Gr a d e 2 ( Q Tc F a v er a g e of 
tri plic at e r e a di n gs > 4 8 0 ms ec) 
R e d uc e d os i n g fr e q u e ncy wit h o ut i nt err u pti o n. If t h e 
e v e nt r ec urs, t h e d os e m a y b e wit h h el d . If t h e e v e nt 
r ec urs a t hir d ti m e , d osi n g m a y o nl y c o nti n u e wit h 
sp o ns or a p pr o v al.  
C CI

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Grade 3 (QTcF average of 
triplicate readings >500 msec) 
 
Withhold AK-01 for up to 14 days. If QTcF returns to 
within 30 msec of baseline or <450 msec within 14 
days, treatment may be resumed at a reduced dosing 
frequency. If the event recurs a second time, the dose 
may again be withheld and resumed after 14 days 
providing the above criteria are met after 14 days. If a 
third occurrence is documented, treatment must be 
terminated. 
Grade 4 (QTcF average of 
triplicate readings >500 msec or 
>60 msec change from baseline, 
and TdP or polymorphic 
ventricular tachycardia or 
signs/symptoms of serious 
arrhythmia) 
Treatment should be terminated. 
Other Non-Hematologic Toxicity 
 
Grade ≤2 
Continue at current dose level. 
Grade 3 (except alopecia, 
nausea, vomiting or diarrhea) not 
optimally managed per 
institutional guidelines 
Withhold AK-01 until event returns to Grade 1 or 
baseline. The first time the event occurs, maintain the 
AK-01 dose level when dosing is resumed.  
Each time the Grade 3 event recurs, withhold AK-01 
until event returns to Grade 1 or baseline, then 
decrease AK-01 dosing frequency- when dosing is 
resumed. If the event recurs at 25 mg QD, the patient 
will be withdrawn. 
Grade 4 (except alopecia, 
nausea, vomiting or diarrhea) not 
optimally managed per 
institutional guidelines 
Patient will be withdrawn. Patient may not be 
rechallenged unless discussed with sponsor and 
approved by the SAC. 
Hematologic Toxicity 
 
Platelets ≤Grade 1 
ANC ≤Grade 1 on Day 1  
and/or 
ANC ≤Grade 2 on Day 8 or 15 
Continue at current dose level. 

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Platelets ≥Grade 2, 
ANC ≥Grade 2 on Day 1, 
ANC ≥Grade 3 on Day 8 or 15, 
and/or  
≥Grade 3 platelets or ANC with 
spontaneous bleeding at any 
time 
Withhold AK-01 until platelets ≤Grade 1 and ANC 
≤Grade 1 (Day 1) or ≤Grade 2 (Day 8 or 15). Consider 
granulocyte colony stimulating factor (G-CSF) for low 
ANC. Decrease AK-01 dosing frequency when dosing is 
resumed.  
Each time the Grade 3 event recurs, withhold AK-01 
until counts recover. Consider G-CSF for low ANC. If 
the event recurs at 25 mg QD, the patient will be 
withdrawn. 
The sponsor must be notified of dose reductions.  Given the P2D of 25mg BID, the only dose 
reduction allowed will be a reduction in dosing frequency from 25mg BID to 25mg QD.  
Following dose reduction and recovery, re-escalation of a patient’s dose will be at the 
discretion of the sponsor in discussion with the investigator.  Re-escalation must not exceed the 
dose at which toxicity was experienced. 
3.4. Discussion of Design and Control 
Phase I is a dose escalation study with a modified 3 + 3 design. The 3+3 design is modified to 
allow expansion of a cohort with 3 additional patients if 1 DLT is observed in 6 patients for a 
total of 9 patients in the cohort (see Figure 2).  The rules-based 3 + 3 method for dose 
escalation is well-established, safe, and does not require real-time PK or computational 
modeling.8 Intrapatient dose escalation is permitted to allow each patient to potentially receive 
a maximum tolerated dose of AK-01 (see Section 3.1.4). In Phase II, preliminary efficacy of AK-
01 will be assessed in up to 4 cohorts (BC, SCLC, TNBC, SCC-HN and/or OT). Preclinical evidence 
indicates AK-01 may be particularly efficacious in these tumor types. 
Since this is not a comparison study, the use of a placebo control is not applicable. 
3.5. Estimated Duration of the Study 
The estimated duration for the entire study is 4-5 years from the time the first patient is 
enrolled in the study until the last patient visit.  
3.6. Determination of Sample Size 
In Phase I, the 3 + 3 design dose escalates cohorts of up to 9 patients until the MTD is identified. 
Up to 6 additional patients may be dosed to inform the selection of a P2D. A sample size of 
approximately 30 patients was considered sufficient to identify the MTD and is not powered on 
the basis of statistical hypothesis testing. 
In Phase II, up to 30 patients for each tumor type will be administered IMP (up to 120 patients 
total). An observed ORR (proportion of partial or complete responders by RECIST) of ≥20% with 
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a durability of at least 4 months will be considered evidence of efficacy. With 15 patients in a 
cohort, there is approximately 60% power to reject the null hypothesis of the ORR being ≤5% 
when the true ORR is 20% using a one-sided exact test for a single proportion at a significance 
level of 0.05. The power for this statistical test for a single tumor type without any adjustment 
for multiplicity is provided in Table 2 using various observed ORRs. 
 Table 2. Statistical Power of Observed Overall Response Rates 
True ORR 
10% 
15% 
20% 
25% 
30% 
N=15 
18% 
40% 
60% 
76% 
87% 
N=20 
13% 
35% 
59% 
78% 
89% 
Thus, whenever the true ORR is at least 20%, a sample size of 15 or 20 patients per tumor type 
provides approximately 60% power to reject the null hypothesis. 
3.7. Study Completion 
The study will be considered complete when all patients enrolled in Phase II have completed at 
least 8 cycles of treatment, experienced disease progression, or discontinued IMP (or 
unacceptable toxicity in the first cohort of Phase I prevents further dose escalation).  
Once a given patient in Phase I or II has completed 8 cycles of treatment, AK-01 administration 
may continue until disease progression, so long as the patient is receiving benefit and is 
experiencing no severe toxicity in the opinion of the investigator. During this period, study 
assessments will be performed as described in Appendix 1. For patient discontinuation 
procedures, see Section 4.2.1.  
3.8. End of Trial 
The end of trial occurs following study completion, after the last patient has discontinued IMP 
and completed any applicable follow-up (Section 3.7). “End of trial” refers to the date of the 
last visit or last scheduled procedure for the last patient in the study. 
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4. STUDY POPULATION
4.1. Criteria for Enrollment 
4.1.1. Inclusion Criteria 
Patients who meet all of the following inclusion criteria will be eligible for enrollment in the 
study: 
1.
Are ≥18 years of age.
2.
Have given written informed consent prior to any study-specific procedures.
3.
Are willing to make themselves available for the duration of the study, and are willing to 
follow study procedures.
4.
Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) 
scale (see Appendix 4).
5.
Have an estimated life expectancy of ≥12 weeks.
6.
Have adequate organ function including:
a. Hematologic: ANC ≥1.5 x 109/L, platelets ≥100 x 109/L, and hemoglobin ≥90 g/L. 
Patients may receive red blood cell transfusions to achieve this hemoglobin level at 
the discretion of the investigator.
b. Hepatic: Albumin ≥30 g/L, bilirubin ≤1.5 times ULN, ALT and AST ≤2.5 times ULN.  If 
the liver has tumor involvement, AST and ALT ≤5 times ULN are acceptable.
c. Renal: Estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2 (see Appendix 
3)
7.
Have discontinued all chemotherapy, investigational therapy, molecularly targeted 
therapy, and cancer-related hormonal therapy at least 14 days prior to study enrollment 
(6 weeks for mitomycin-C or nitrosoureas).
8.
Have discontinued biologic therapy and immunotherapy at least 21 days prior to study 
enrollment or have recovered from all AE to baseline or Grade 1 with the exception of 
alopecia or Grade 2 neuropathy.
9.
Patients who have had radiation therapy must be fully recovered in the opinion of the 
investigator prior to enrolling on study.
10. Are recovered or recovering from the acute adverse effects of any chemotherapy, biologic 
therapy, immunotherapy, molecularly-targeted therapy, cancer-related hormonal 
therapy, and investigational therapy (≤Grade 1 or baseline), with the exception of alopecia 
or Grade 2 neuropathy.
11. Have received at least 1 but no more than 4 lines or regimen of prior systemic therapies 
for locally advanced or metastatic disease. Hormone therapies are not considered in the 
determination of number of prior lines of systemic therapies.
12. Patients who have had surgery must be fully recovered in the opinion of the investigator 
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13. Female patients with reproductive potential must agree to use 2 forms of highly effective
contraception during the study and for at least 3 months following the last dose of IMP.
Sexually active male patients must use a barrier method of contraception (condom)
during the study and for at least 3 months following the last dose of IMP.
14. Females with child-bearing potential must have had a negative pregnancy test result
≤28 days prior to the first dose of IMP, as well as ≤1 day prior to the first dose of IMP.
15. Patients must be, in the judgment of the investigator, appropriate candidates for
experimental therapy, and no standard therapy would confer clinical benefit to the
patients.
Phase I 
16. Patients must have histological or cytological evidence of cancer (solid tumors, excluding
primary brain tumor) that is evaluable, and locally advanced and/or metastatic.
Phase II 
17. Patients must have disease that is measurable by RECIST v.1.1 (see Appendix 10).
18. Patients must have histological or cytological evidence of a solid tumor that is locally 
advanced and/or metastatic and have failed locally approved therapies that have clinical 
benefit as follows:
a. SCLC
• Must have failed platinum-containing therapy but be in a platinum sensitive 
relapse (having responded to up to 6 cycles of platinum therapy with at least 
SD, PR, or CR, and then maintained that response without progression for
3 months after the last platinum dose. Patients could have received 
maintenance therapy following the completion of platinum therapy. Patients 
who never responded or progresses < 3 months after the last platinum dose are 
not eligible).
b. BC
• ER+ and/or PR+ but HER2-negative (see Appendix 8 for eligible biomarker 
expression).
• May have failed up to 2 prior chemotherapy regimens.
• Must have failed a hormone therapy and a CDK4/6 inhibitor.
c. TNBC
• Must have recurrent/refractory TNBC, defined as any breast cancer that 
expresses <1% ER, <1% PR, and is HER2-negative (immunohistochemistry 
staining of 0 or +1, or no evidence of amplification using single or
dual- probe- in situ hybridization).  Must have failed standard therapy.
d. SCC-HN
• For HPV associated SCC-HN, must have failed standard therapy.
e. OT 

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•
T o b e d et er mi n e d  b y t h e s p o ns or.
4. 1. 2.  Excl usi o n Crit eri a  
P ati e nt s w h o m e et t h e f oll o wi n g crit eri a will b e excl u d e d fr o m t h e st u d y: 
1 9. H a v e  me dic al  co n diti o ns  t h at, in  th e  o pi ni o n  of t h e in v esti g at or,  wo ul d pr ecl u d e  
p artici p ati o n i n t his st u d y s uc h as o v er w h el mi n g  inf ecti o ns.
2 0. H a v e  sy m pt o m a tic c e ntr al nerv o us  syst e m  ( C NS ) m et ast asis.  P ati e nt s wit h tre at e d C N S  
m et ast asis  ar e  eli gi bl e if th e y  ar e as y m pt o m atic  an d n ot  curr e ntl y  r ec ei vi n g 
c ortic ost er oi ds. Scr e e ni n g  of  asy m pt o m atic  p ati e nt s wit h o ut a hist or y  of  CN S m et ast as is is 
n ot  r eq uir e d.
2 1. H a v e  a pri m ar y  tu m or  of t h e C N S .
2 2. H a v e  a hist or y  of or g a n  tr a ns pl a nt (e. g.,  h e art,  lu n gs,  li ver,  b o n e  m arr o w, or  ki d n ey).
2 3. F e m al es  wh o  ar e pr e g n a nt o r n ursi n g.
2 4. H av e  s y m pt o m atic h u m a n  i m mu n o d efici e nc y  vir us ( HI V) i nf ecti o n, k n o w n  HI V  p ositi v e  t est 
res ults o r h a v e  chr o nic  acti v e h e p atitis  B or C  (scr e e ni n g is not  r e q uir e d).
2 5. H av e  cli nic all y si g nific a nt car di ac  dis e as e incl u di n g  a ny  of t h e foll o wi n g:
•
A hist or y  of c o n g e nit al lo n g  QT  sy n dr o m e,  s y m pt o m atic br a d yc ar di a, v e ntric ul ar  
arr h yt h mi a,  unc o n tr oll e d atri al fi brill ati o n, s ec o n d or t hir d d e gr e e h e art  bl oc k, or  
ot h er  co n d ucti o n  ab n or m alit y  th at  in  th e  o pi ni o n of t h e  in v esti g at or  wo ul d  
pr ecl u d e  saf e  p artici p ati o n i n t his st u d y.
•
C o n g esti v e  he art  fail ur e  (N e w  Yor k  He art  Ass oci ati o n Cl ass ≥3;  s ee A p p e n d ix 5).
•
U n st a bl e a n gi n a  p ect oris, ac ut e m y oc ar di al i nf arcti o n , or str o k e ≤1 2  m o nt hs  pri or  
t o enr oll m e nt.
•
Q Tc F  pr ol o n g ati o n  > 4 5 0 m s ec.
2 6.
 
2 7. H av e  > Gr a d e  1 h y p o k al e mi a , hy p o m a g n es e mi a,  or h y p oc alc e mi a  whic h  ca n n ot  b e  
c ontr oll e d  pri or t o  enr oll m e nt.
2 8. H a v e  a hist or y  of maj or  sur g er y  t o t h e u p p er  g astr oi nt esti n al ( GI ) tr act, GI  dis e as e or ot h er 
m e dic al  co n diti o n  t h at i n th e  o pi ni o n  of t h e in v esti g at or  ma y  int erf er e  wit h or al dr u g 
a bs or pti o n .
2 9. Ar e  a f a mil y me m b er o f t h e in v esti g at or  or  st aff of t h e st u d y sit e.
3 0. Ar e  curr e ntl y  enr oll e d  i n a n ot h er  cli nic al st u d y of a n  i n v esti g atio n al t h er a py .
3 1. Pr e vi o us  th er a p y  wit h a n Aur o r a ki n as e  i nhi bit or.
3 2. H y p ers e nsiti vit y  to  an y  co m p o n e nts  of A K- 01 . 
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4.2. Discontinuation 
4.2.1. Discontinuation of Patients 
In accordance with the guidelines of the International Conference on Harmonisation (ICH) Good 
Clinical Practices (GCP), Health Canada, European Medicines Agency, and United States Food 
and Drug Administration, a patient may withdraw their participation in this study at any time. 
Criteria to discontinue patients from study treatment will include but will not be limited to: 
•
Objective disease progression based on RECIST v. 1.1 as determined by the investigator
•
Unacceptable toxicity
•
Significant protocol violation
•
Global deterioration of health status
•
Lost to follow-up
•
Refusal of further treatment by patient
•
Study termination by sponsor
•
Dosing is delayed by more than 21 days due to toxicity
Reasons for discontinuation from the study may include: 
•
Study termination by sponsor
•
Lost to follow-up
•
Withdrawal of consent
If a patient is found to not meet the enrollment criteria but was inadvertently enrolled, the 
patient must be discontinued from the study and the sponsor or its designee must be informed. 
An exception to this requirement may be granted in rare circumstances where the patient has a 
serious or life threatening condition for which there is no effective alternative therapy and, in 
the opinion of the investigator, is receiving benefit from study treatment. In this case, the 
investigator must obtain documented approval from the sponsor’s medical representative to 
allow the patient to continue receiving IMP. 
Following discontinuation or withdrawal, the investigator will request that the patient return all 
unused IMP and packaging, and participate in the Discontinuation and 30-Day Follow-up visits. 
If it is in the best interest of the patient to start a new anti-cancer treatment prior to this date, 
the follow-up assessments may be performed sooner, so long as they are completed prior to 
initiation of the new therapy. 
The primary reason for withdrawal, patient outcome, and the date of withdrawal will be 
documented. Every effort will be made to adequately follow the patient for any unresolved AEs. 
In the case of withdrawal due to global deterioration of health status, the signs, symptoms, or 
results that motivated this decision will be documented.  
If the patient withdraws from the study and also withdraws consent for disclosure of future 
information, no further evaluations will be performed and no additional data will be collected. 
The sponsor may retain and continue to use any data collected before the withdrawal of 
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Discontinued patients may be replaced in the study, as described in Section 5.3.2. 
4.2.2. Discontinuation of Study Centers 
Study center participation may be discontinued by the sponsor, the investigator, or the 
Institutional Ethics Committee/Institutional Research Board (IEC/IRB) for any reason (e.g., legal, 
regulatory, non-performance, or GCP compliance issues). 
4.2.3. Discontinuation of the Study 
This clinical study may be prematurely terminated, patient enrollment may be suspended, or 
IMP administration may be halted due to a decision by a regulatory authority, a change in 
opinion of the IEC/IRB, safety concerns, or at the discretion of the sponsor. The sponsor retains 
the right to discontinue development of the IMP at any time. If the study is prematurely 
terminated, the sponsor will promptly notify the investigator. The investigator may also 
terminate the study at his/her study center for reasonable cause, if written notice is provided 
to the sponsor in advance of the intended termination.  
The occurrence of any of the following in any patient in any part of this study will prompt an 
immediate suspension of patient enrollment and IMP administration: 
• Death in any patient which the investigator deems to be possibly related to 
administration of the IMP. 
• Any other event which is considered sufficiently serious by the investigator or the 
medical representative of the sponsor to warrant immediate safety review. 
A cumulative review of safety data and the AE in question must be promptly conducted by the 
SAC to determine whether to resume the study, modify the protocol, or permanently terminate 
the study. If the SAC recommends permanent termination of the study, the sponsor will provide 
instructions to the investigators. 

A U R A -0 0 1  
1 0/ A pr/ 2 0 1 8  
Cli nic al St u d y Pr ot oc ol  
V ersi o n 4   
 
 
A ur K a P h ar m a, I nc. — C o nfi d e nti al  
P a g e 3 1  of 9 9  
 
5.  T R E A T M E N T  
5. 1.  R ati o n al e f or S el ecti o n of D os e  
Pr ecli nic al G o o d L a b or at or y Pr actic e  t oxic ol o g y st u di es i d e ntifi e d  
 as t h e hi g h est n o n -
s e v er el y t oxic d os e ( H N S T D) i n d o gs. T h e s af e st arti n g  d os e w as c alc ul at e d as o n e -sixt h t h e 
H N S T D a dj ust e d f or b o dy s urf ac e ar e a , 
 
C o ns e q u e ntl y, t h e st arti n g d os e f or P h as e I  w as c h os e n t o b e 2 5  m g  BI D  (5 0  m g  d ail y ). 
Esc al ati o n b e y o n d t his d os e will b e g ui d e d b y s af et y , ex p os ur e , a n d P D d at a  (as a v ail a bl e ) u ntil 
a n M T D is est a blis h e d or t h e hi g h est pl a n n e d d os e of 8 0 0 m g BI D  is r e ac h e d. 
A P K/ P D m o d el f or effic acy i n a muri n e  x e n o gr aft t u m or m o d el s u p p ort e d i n vitr o fi n di n gs t h at 
A K -0 1 c o nc e ntr ati o ns a b o v e I C 9 0 elicit c ell d e at h a n d t u m or gr o wt h i n hi biti o n.  T h us, t h e t ar g et 
f or effic acy us e d t o pr oj ect t h e h u m a n effic aci o us d os e r a n g e w as 9 0 % i n hi biti o n of p A ur A 
m ai nt ai n e d o v er t w o -t hir ds of t h e d osi n g i nt er v al (i. e., 8 h o urs f or t wic e d ail y d osi n g).  T wic e  
d ail y d osi n g is s u g g est e d t o m ai nt ai n a d e q u at e ti m e o n t ar g et.
 
 
  
T h e 2 5 m g BI D h as b e e n c h os e n b y t h e S A C a n d s p o ns or as t h e d os e of P h as e II . D os e s el ecti o n 
w as b as e d o n t h e M T D, A ur A a n d A ur B t ar g et e n g a g e m e nt, a n d P K fr o m P h as e  I (s e e S ecti o n 
3. 1. 3 ). 
F urt h er d et ails o n t h e r ati o n al e f or d os e s el ecti o n m a y b e f o u n d i n t h e I n v esti g at or’s Br oc h ur e. 
5. 2.  I n v esti g ati o n al M e dici n al Pr o d uct  
A K -0 1 dr u g pr o d uct  will b e s u p pli e d b y t h e s p o ns or as c a ps ul es  c o nt ai ni n g 2 5 m g A K --0 1 dr u g 
s u bst a nc e a n d n o i n acti v e i n gr e di e nts . A K -0 1 I M P c o nsists of b ottl es c o nt ai ni n g 1 6 c a ps ul es of 
2 5 m g, w hic h will b e s u p pli e d t o t h e d esi g n at e d p h ar m acy of e ac h st u d y c e nt er.  
I M P will b e s u p pli e d b y t h e s p o ns or. T h e s p o ns or is r es p o nsi bl e f or e ns uri n g t h at I M P is 
m a n uf act ur e d acc or di n g t o c urr e nt G o o d M a n uf act uri n g Pr actic e r e g ul ati o ns a n d r e q uir e m e nts, 
a n d t h at  l a b eli n g m e ets a n y l oc al r e g ul ati o ns . 
All s u p pli e d I M P will b e f or i n v esti g ati o n al us e o nly a n d will o nl y b e dis p e ns e d t o p ati e nt s 
e nr oll e d i n t his st u d y.  T h e in v esti g at or or d esi g n e e will e ns ur e t h at all I M P is m ai nt ai n e d i n a 
r estrict e d ar e a acc or di n g t o r e g ul at or y a n d st u d y c e nt er r e q uir e m e nts. I M P will b e st or e d at 
r o o m t e m p er at ur e ( 1 5˚ C -3 0˚ C)  at t h e st u d y c e nt er , a n d p ati e nt s will b e i nstr uct e d t o st or e I M P 
dis p e ns e d f or h o m e a d mi nistr ati o n at r o o m t e m p er at ur e.  
Pr e p ar ati o n, dis p e nsi n g, a n d st or a g e of I M P will f oll o w r o uti n e p h ar m acy pr oc e d ur es. H a n dli n g 
s h o ul d b e li mit e d t o i n divi d u als i n v ol v e d i n dis p e nsi n g a n d a d mi nist eri n g I M P (i ncl u di n g t h e 
p ati e nt s f or h o m e a d mi nistr ati o n).  
P ati e nt s will  b e dis p e ns e d  I M P as f oll o ws: D a ys 1, 8, a n d 1 5 f or Cycl e 1  of P h as e I , D a y 1 f or 
Cycl es ≥2 of P h as e I , a n d D a y 1 f or all cycl es of P h as e II . A K -0 1  m a y b e dis p e ns e d u p t o 2 d a ys 
pri or t o e ac h sc h e d ul e d dis p e nsi n g d a y t o f acilit at e p ati e nt sc h e d uli n g.  
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5.2.1. Investigational Medicinal Product Administration 
Doses of AK-01 taken at the study center will be administered by trained study personnel and 
will be recorded. Any dose reductions or dose interruptions will be recorded with the 
associated reasons. Patients will be given instructions for home dosing. Confirmation of home 
administration will be based on measurements of treatment compliance (see Section 8.1.5). 
AK-01 should be taken orally according to the assigned dosing schedule and the investigator’s 
instructions. Patients will take AK-01 twice a day approximately 12 hours apart. Patients will be 
encouraged to fast for 1 hour prior and 1 hour following each dose. 
Doses of AK-01 should be taken at approximately the same time each day during the dosing 
period. If a dose of AK-01 is missed, it should be reported as such and should not be combined 
with a dose on another day. If a dose of AK-01 is vomited, it should be reported as such and 
should not be repeated.  
5.2.2. Dose and Regimen 
AK-01 will be administered twice daily, every day of a 21-day cycle. Patients will be dosed 
continuously: there will be no dosing holiday between cycles. 
In Phase I, the dose of AK-01 will be between 25-75 mg BID per day (see Table 3). Patients in 
the first cohort of Phase I will receive 25 mg BID AK-01. Following a review of safety and other 
relevant data from this cohort, the SAC will decide on the dose for the subsequent cohort based 
on Table 3. Following DLT or completion of Cycle 1, dosing for a given patient will be based on 
individual safety and tolerability. 
For Phase II, the sponsor and SAC has established the dose of AK--01 as 25mg BID. 
Table 3. AK-01 Dosing  
Dose Level 
Capsules Administered 
Total Daily Dose 
25 mg QD 
1 × 25 mg 
25 mg 
25 mg BID 
1 × 25 mg (morning) 
1 × 25 mg (evening) 
50 mg 
The dose of AK-01 may be reduced and/or interrupted for toxicity as described in Section 3.3.2. 
After monitoring visits, at study completion and after the close-out visit, unused AK-01 and 
dispensed medication bottles returned by patients will be sent to the sponsor or designee, 
unless the sponsor and study centers have agreed to destruction of AK-01 by the study center, 
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5.3. Method of Assignment to Treatment 
This study will be open-label and will not involve a randomization schedule. In Phase I when a 
cohort requires an additional patient, the priority to enroll a patient will be given to each center 
consecutively. 
In Phase II a patient’s tumor type will determine their allocation to cohort. Study centers will 
enroll competitively as eligible patients become available.  The patients will be allocated to IMP 
only after the registration form is signed by both the investigator and sponsor representative. 
5.3.1. Special Treatment Considerations 
Patients will attend scheduled clinic visits (see  Appendix 1) and comply with study criteria 
under their control. Any deviation from the prescribed dose or regimen will be recorded. 
5.3.2. Evaluable Patients 
Any patient who withdraws from the study before receiving IMP may be replaced. 
Any patient in Phase I who is discontinued from the study before completing Cycle 1 or who 
receives ˂38 doses of IMP in Cycle 1 will be deemed non-evaluable for DLT assessment at that 
dose level, unless the patient experiences a DLT. Additional patients may be enrolled to a 
cohort in Cycle 1 if a patient is withdrawn for reasons other than a DLT (e.g., disease 
progression, non-compliance, or personal reasons) to ensure that an appropriate number of 
patients will be evaluated.  
Any patient withdrawn for toxicity in Cycle ≥2 of Phase I will not be replaced.  
Any patient withdrawn for toxicity in Phase II prior to completion of Cycle 1 may be replaced. 
Any patient who is not evaluable for PK, PD, or biomarkers may be replaced upon consultation 
with the investigator(s) and the sponsor to ensure collection of sufficient data for 
interpretation. 
5.4. Specific Restrictions/Requirements 
All patients must be available at the study center for approximately 8 hours on Day 1 of Cycle 1 
for administration of the first dose of AK-01, PK sampling, and safety assessments. Patients 
must also be available at the study center for approximately 8 hours after the first dose on Day 
15 of Cycle 1 in order to perform PK sampling and safety assessments.  
Tumor biopsy will involve observation for safety monitoring according to the institutional 
standard of care (typically 4-6 hours). 
Periodic visits to the study center will also be necessary as described in the schedule of events 
(Appendix 1). 
5.5. Blinding 
This will be an open-label study. 
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A U R A -0 0 1  
1 0/ A pr/ 2 0 1 8  
Cli nic al St u d y Pr ot oc ol  
V ersi o n 4  
5. 6.  C o nc o mit a nt T h er a p y  
A ll c o nc o mit a nt m e dic ati o n  a d mi nist er e d  fr o m th e  tim e  of first d os e u ntil  t h e last  d os e o f I M P 
m ust  be  r ec or d e d, al o n g  wit h t h e r eas o n  f or us e a n d  d at e  of ad mi nistr ati o n . T his  i ncl u d es o v er -
t h e-co u nt er  or pr escri b e d m edic ati o ns,  vita mi ns  an d h er b al  su p pl e m e nts.   
All c o nc o mit a nt  m edic ati o n  ad mi nist er e d  t o tr e at a n  on g oi n g  A E or s eri o us ad v ers e  e ve nt  (S A E ) 
m ust b e  rec or d e d u ntil  th e  e v e nts  r es ol v e, t h e ev e nts  ar e n o l o n g er co nsi d er e d t o b e dru g -
r el at e d, t h e p ati e nt di es  or is l ost to  foll o w -u p,  or a n e w  tr e at m e nt is initi at e d  f or th e  p ati e nt.  
W hil e  on st u d y,  p ati e nts m a y  b e a d mi nist er e d m e dic ati o ns  at th e  discr eti o n of t h e  in v esti g at or 
to  tre a t A E s or as su p p orti v e  car e  ( e. g., anti -e m etics , a ntibi ot ics, etc.). 
B C  p ati e nts  on a  st a bl e re gi m e n of  b o n e  h e alt h  ag e nts  (e. g.,  s el ecti v e estr o g e n r ec e pt or 
m o d ul at ors , bis p h os p h o n at es, etc.) m a y  co nti n u e  tre at m e nt .  
H e m at o p o eitic  gr o wt h fact ors  (e. g.,  er yt hr o p o eiti n, G-C S F ) m a y  b e  a d mi nist er e d  i n this  st u d y 
acc or di n g  to  instit u ti o n al gui d eli n es  exc e pt  in  Cycle  1 of P h as e  I.  H e m at o p o eitic  gr o wt h f act ors  
will b e  allo w e d  in  Cycl e  1 of Ph as e  I if a pati e nt  ex p eri e nc es ne utr o p e ni a  th at  is decl ar e d  a DL T.  
Bl o o d pr o d uct tr a nsf usi o ns  will b e  per mitt e d  t hr o u g h o ut t h e st u d y 
 
 
 
O t h er ch e m o t h er a p y, i n v esti g ati o n al th er a p y,  m ol ec ul arl y-t ar g et e d t h er a py a n d c a nc er-r el at e d 
h or m o n e  th er a p y  will b e  pro hi bit e d  wi t hi n 1 4 d a ys  pri or  to  st u d y e nr oll m e nt  (6 w e e ks  for  
mit o m yci n -C  or nitr os o ur e as) a n d  thr o u g h o ut  th e  st u d y. Bi ol o gic  th er a p y  an d  i mm u n ot h er a p y  
will  b e pr o hi bit e d  wit hin 2 1  da ys  pri or  t o st u d y enr oll m e nt a n d  thr o u g h o ut  t he  st u d y. 
R a di o t h er a p y t o n o n-t ar g et lesi o n s w ill b e  p er mitt e d  on  st u d y if a p pr o v ed b y  th e  sp o ns or . 
A ntic o a g ul a nts  (e. g.,  or al a ntic oa g ul a nts,  lo w  m ol ec ul ar w ei g ht h e p ari n) , a nti pl at el ets  (e. g.,  
ac et yls alicylic  aci d, P2 Y 1 2  i nhi bit ors),  a n d n o nst er oi d al  anti -i nfl a m m at or y dr u gs (e. g.,  i b u pr of e n, 
n a pr ox e n)  s h o ul d be  st o p p e d pri or t o tu m or  bi o ps y  acc or di n g  t o instit uti o n al pr actic e . 
A n y  p ati e nt with q u esti o ns  re g a r di n g co nc o mit a nt t h er a pi es  will b e  as k e d t o co nt act  th e  
i n v esti g at or. 
A ur K a  P har m a,  I nc. — C o nfi d e nti al  
P a g e 3 4  o f 9 9  
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6. PHARMACOKINETIC, PHARMACODYNAMIC, SAFETY AND EFFICACY DATA COLLECTION
All supplies for collection and shipment of blood and tissue samples for PK, PD, and molecular 
profiling will be provided. Further instructions will be provided on sample collection, 
processing, storage, and access.  
6.1. Pharmacokinetic Evaluations 
6.1.1. Samples for Pharmacokinetic Evaluations 
At the visits and times specified in the schedule of events (Appendix 1), venous blood samples 
of approximately 3 mL will be collected from all patients to determine the plasma 
concentrations of AK-01. The actual date and time (24-hour clock time) of each sampling will be 
recorded. Pre-dose samples should be obtained no more than 1 hour prior to dosing. The 
sampling schedule may be modified following review of PK data from the first cohort in Phase I 
to optimize collection times. 
A maximum of 3 additional PK samples may be drawn at other time points during the study, if 
warranted and agreed upon by both the investigator and the sponsor. 
6.1.2. Bioassay 
Samples for AK-01 concentration will be analyzed using a validated tandem liquid-
chromatography/mass spectrometry method at a laboratory designated by the sponsor. 
6.2. Pharmacodynamic Evaluations 
6.2.1. Samples for Pharmacodynamic Evaluations 
Hematology samples (see Appendix_1) will be used to evaluate a variety of hematological 
parameters, including white blood cell count, neutrophil count, and lymphocyte count. Changes 
in hematological parameters may be compared across time points and to AK-01 PK. 
In Phase I, pre-treatment and on-treatment skin biopsies will be mandatory for all patients (see  
Appendix 1). For all Phase I patients enrolled in the P2D confirmation cohorts (after 
identification of the MTD, see Section 3.1.3), pre-treatment and on-treatment biopsies of 
primary or metastatic tumor will also be required (see  Appendix 1). For all patients enrolled in 
Phase II, tumor biopsies will be required from either a primary or metastatic tumor site.  SCLC 
patients tumor biopsies will be required unless the primary or metastatic tumor site is 
inaccessible or a quality biopsy cannot be obtained. The initial tumor biopsy should be collected 
after the patients previously failed therapy and prior to C1D1, and the second biopsy should be 
collected at C2D8, ± 3 days.  Archived specimen(s) from a diagnostic biopsy and/or surgery of 
the tumor may be requested instead of pre-treatment tumor biopsy as long as the biopsy was 
obtained after they had already failed previously therapy. Tumor samples may be used for both 
PD and molecular profile analyses (see Section 6.3). 
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6.2.2. Evaluation of Target Engagement 
Markers of dose-dependent target engagement will be evaluated, which may include 
assessment of levels of phospho-histone H3 and markers of apoptosis, phosphorylation, DNA 
damage, and mitosis.  Samples may be assessed using immunohistochemistry, Western 
blotting, ELISA, or other techniques, and will be compared across time points. The inhibition of 
AurA and AurB by AK-01 will be compared. Markers of dose-dependent target engagement may 
be compared between skin (collected in phase I) and tumor tissue. 
6.3. Molecular Profile Evaluation 
6.3.1. Samples for Molecular Profile Evaluations 
A pre-treatment tumor biopsy is required for all patients in Phase II for assessment of molecular 
profile (SCLC tumor/metastatic site biopsies are collected if possible). If available, archived 
sample(s) from a diagnostic biopsy/surgery of the primary or metastatic tumor collected prior 
to enrollment may be requested instead as long as the biopsy was obtained after they had 
already failed previously therapy. Any other tumor samples collected in the course of the study 
may also be profiled (see Section 6.2.1).  
Blood samples for molecular profiling will be collected on Day 1 of every cycle and at 
discontinuation.  
6.3.2. Evaluation of Molecular Profile 
DNA and/or proteins from tumor samples and blood may be analyzed using immunohisto 
chemistry staining, next generation sequencing or other technology to identify the presence of 
certain proteins or DNA mutations (e.g., Rb, PTEN, myc, and TP53). Somatic mutations may be 
identified through analysis of paired data from tumor tissue and blood, if data is not already 
available in patient histories. These samples may be used to evaluate the genetic mechanisms 
underlying response to AK-01. 
Measures of efficacy may be compared between patients with different molecular tumor 
profiles. 
6.4. Storage of Samples 
Biological samples collected for analysis of PD or molecular profile (i.e., blood, serum, plasma, 
skin (phase I only), and tumor tissue) will be retained for a maximum of 15 years following the 
last patient visit. 
Samples collected for specified laboratory tests will be destroyed within 60 days of receipt of 
confirmed test results. When scientific circumstances warrant, it is acceptable to retain samples 
until the end of the study to confirm the validity of the results. Certain samples may be retained 
for a longer period if necessary to comply with applicable laws, regulations, or laboratory 
certification standards. 

A U R A -0 0 1  
1 0/ A pr/ 2 0 1 8  
Cli nic al St u d y Pr ot oc ol  
V ersi o n 4  
Bi o a n al ytic al s a m pl es  coll ect e d  to  m eas ur e  A K -0 1  c o nc e ntr ati on will  b e r et ai n e d for a  m axi m u m 
of  1 ye ar f oll o wi n g l ast p ati e nt  visit f or  t h e st u d y ( u nl ess loc a l/ n ati o n al r e g ul ati o ns sti p ul at e 
l o n g er). Duri n g  this  ti m e, sa m pl e s r e m ai ni n g aft er bi o a n al ys is m a y  be  us e d  f or ot h er  descri b e d  
a n al ys es.  
6. 5.  S af e t y E v al u ati o ns 
6. 5. 1.  S af et y M e as ur es  
T his  st u d y co nt ai ns  d et ail e d s af et y  m o nit ori n g  t h at will per mit c h ar act eriz ati o n  of th e  saf et y 
pr ofil e  of A K - 01  i n p ati e nts wit h l oc all y ad v a nc e d  or m et ast atic  t u m ors. S ee   A p p e n dix  1  f or t he 
sc h e d ul e of s af et y ass ess m e nts.  
6. 5. 2.  S af et y  D at a C oll ecti o n a n d R evi e w  
T h e  in v esti g at or  is res p o nsi bl e  f or th e  saf et y  of al l p ati e nt s r eg ist er e d in  t his cli nic al st u d y. 
F or  all sc h e d ul e d an d u nsc h e d ul e d s af et y  ass ess m e nts , t h e r es ults a n d  inv esti g at or’s  
ass ess m e nt  of cli nic al si g nific a nc e will b e r ec or d e d (i. e., cli nic al l a b or at or y ev al u ati o ns  
[h e m at ol o g y,  cli nic al c h e mistr y, en d ocri n ol o g y,  an d  uri n al ysis],  EC O G  st at us, el ectr oc ar di o gr a m 
[E C G ], vit al si g ns, a n d  physic al ex a m).   
All E C Gs  will b e 12 -le a d  tri plic at e ass ess m e nts obt ai n e d  usi n g di gital e q ui p m e nt  a ppr oxi m at el y 
5  mi nut es  a part  at t h e  tim e  p oi nts  in dic at e d i n  A p p e n dix  1.  
 
 
 
 
 A d di ti o n al EC Gs  ma y  b e obt ai n e d  if m edic all y  warr a nt e d . W h e n a n  EC G  is sc h e d ul e d 
o n  t h e sa m e  d a y  as a bl o o d  coll ecti o n,  th e  E C G  will b e obt ai n e d  pri or t o  bl o o d  coll ecti o n.  A n y 
cli nic all y si g nific a nt E C G  r es ult will b e d oc u m e nt e d as  an  A E.  T h e  in v esti g at or  ma y  co n d uct  an  
ec h oc ar di o gr a m ( E C H O ) e v al u ati o n  if cli nic all y i ndic at e d. 
Cli nic al l a b or at or y  tests  ar e  list e d in  A p p e n dix  2.  F or all cli nic al l a b or at or y  s af et y t ests, a 
c ertifi e d loc al l a b or at or y  will b e  us e d  to  perf or m l a b or at or y  an al ys es  to  gui d e  tre at m e nt  
d ecisi o ns  an d  dat a a n al ysis.  Q u alifi e d  m edic al st a ff will r e vi e w, i niti al a n d  d at e  all l a b or at or y  
r es ults. 
M or e  ad v a nc e d o p ht h al m ol o gic  ex a ms ma y  b e do n e  at t h e re q u est o f t h e in v esti g at or  if 
n e e d e d.  
A n  A E will b e r ec or d e d f or t h e r es ult of a n y s af ety ass ess m e nt (e. g.,  EC G,  vit al si g ns,  cli nic al 
c h e mistr y val u e,  etc.) t h at r e q uir es a  p ati e nt t o be  disc o nti n u e d fr o m t he  st u d y or rec ei v e  
tr e at m e nt. T h e  me dic al  co n diti o n  ca us e d b y  th e  ab n or m al  res ult  sh o ul d  be  r ec or d e d, r ath er 
th a n  t h e a bn or m al  r es ult ( e. g., hy p er gl yc e mi a  i nst e a d of el e v at e d  gl uc os e). F or t h e  r es ult of a n y  
A ur K a  P har m a,  I nc. — C o nfi d e nti al  
P a g e 3 7  o f 9 9  
C CI

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safety assessment which requires a patient to be discontinued or receive treatment, the 
investigator will follow the AE to a satisfactory clinical resolution. 
6.5.3. Adverse Events 
The sponsor has standards for reporting AEs that are to be followed regardless of applicable 
regulatory requirements that may be less stringent. A clinical trial AE is any untoward medical 
event associated with the use of a drug in humans, whether or not it is considered related to 
that drug. Lack of drug effect is not an AE in clinical trials, because the purpose of the clinical 
trial is to establish drug effect.  
The investigator, medical monitor, and sponsor will review the collected data regularly for 
evidence of AEs.  All patients will be assessed routinely for AEs as outlined in the schedule of 
events (Appendix 1). All AEs must be reported to the sponsor or its designee regardless of 
relatedness to IMP or protocol procedures from the time the patient signs the informed 
consent documents (ICD) to when the patient receives the last dose of IMP. Thereafter, AEs will 
only be reported if ongoing or considered related (possibly or probably) to the IMP.  
The investigator will notify the sponsor or designee prior to reducing a patient’s dose or 
discontinuing treatment. If a patient’s dose is reduced or treatment is discontinued as the 
result of an AE, study personnel will clearly document the circumstances and data leading to 
dose reduction/treatment discontinuation. 
While the patient is on study, study personnel will record any change in medical history or 
preexisting condition(s). Events leading to the clinical outcome of death due to progression will 
be included as part of the safety and efficacy analyses for this study, but will not require 
immediate reporting to the sponsor or its designee as AEs, unless the investigator believes the 
event may have been caused by the IMP. Signs and symptoms of progression of the disease 
under study will not be considered AEs in this study. 
Cases of pregnancy that occur during maternal or paternal exposures to IMP will be reported. 
Data on fetal outcome and breast-feeding are collected for regulatory reporting and drug safety 
evaluation. Upon documentation of pregnancy, the patient must be removed from the study, 
and treatment with IMP must be stopped immediately. 
The investigator will decide whether he or she interprets the observed safety signals as related 
to the IMP. To assess the relationship of the AE to administration of AK-01, the following 
terminologies are defined: 
•
Probably related: a direct cause and effect relationship between the IMP and the AE is
likely.
•
Possibly related: a cause and effect relationship between the IMP and the AE has not
been demonstrated at this time and is not probable, but is also not impossible.
•
Unlikely: likely to be due to another etiology.
•
Not related: without question, the AE is definitely not associated with the IMP.
The severity of all AEs will be graded using CTCAE version 4.03. Table 4 presents general 
guidelines for evaluating severity by CTCAE; see Appendix 9 for severity guidelines by 
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Table 4. CTCAE Guidelines for Evaluation of AE Severity 
Clinical Description of Severity 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living (e.g., preparing 
meals, shopping for groceries or clothes, using the telephone, managing 
money, etc.) 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care activities of daily living (e.g., bathing, dressing and 
undressing, feeding self, using the toilet, taking medications, and not 
bedridden) 
Grade 4 
Life-threatening consequences; urgent intervention indicated 
Grade 5 
Death related to AE 
Severity and seriousness are not equivalent: an AE may be severe in intensity, but would be 
considered serious only if it meets the criteria for an SAE (described in Section 6.5.4). If an AE is 
deemed serious, the CTCAE severity grade reported must be consistent with this assessment.  
6.5.4. Serious Adverse Events 
Study center personnel must alert the sponsor or its designee of any serious adverse event 
(SAE) within 24 hours following investigator knowledge of the event via a sponsor-approved 
method. Alerts issued via telephone must be immediately followed with official notification on 
study-specific SAE forms. An SAE is any AE from this study that results in one of the following 
outcomes: 
•
Death
•
Initial or prolonged inpatient hospitalization
•
A life-threatening experience (that is, immediate risk of dying)
•
Persistent or significant disability/incapacity
•
Congenital anomaly/birth defect
•
Considered significant by the investigator for any other reason.
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious adverse drug events when, based on appropriate 
medical judgment, they may jeopardize the patient and may require medical or surgical 
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not be reported as SAEs, however if an AE occurs during hospitalization for preplanned surgery 
that meets the above criteria, it will be reported as an SAE. SAEs due to progressive disease 
(including death) should not be reported as SAEs unless the investigator also deems there is a 
possible contribution of the IMP. 
All SAEs occurring from the time the patient signs the ICD until the 30-day Follow-up visit must 
be reported to the sponsor or its designee regardless of relatedness to IMP or protocol 
procedures. Thereafter, SAEs will be reported only if the investigator feels the events were 
related to the IMP or a protocol procedure. Any SAEs after ICD signature and prior to 
administrion of IMP will be reported if the investigator feels the events were related to a 
protocol procedure. 
 Appendix 1 outlines specific safety assessments for the 30-day Follow-up visit. All drug-related 
AE and SAEs will be followed until the events resolve, the events are no longer considered to be 
drug-related, the patient dies or is lost to follow-up, or until a new treatment is initiated for the 
patient. Frequency of follow-up evaluation is left to the discretion of the investigator.  
The medical representative of the sponsor will monitor safety data throughout the course of 
the study. The sponsor and/or its designee will review SAEs within appropriate timeframes to 
meet reporting obligations imposed by regulatory authorities. All serious and unexpected AEs 
for this study will be reported to regulatory authorities in accordance with local laws, directives 
and regulations. 
6.5.5. Safety Assessment Committee 
A SAC will be involved in safety oversight and decisions of dose escalation during the course of 
the study. Members of the SAC will include the Principal Investigator or designee from each 
actively enrolling study center, the medical representative(s) of the sponsor, and other 
representatives, as necessary. A SAC chair will be chosen. The SAC will meet by teleconference 
to cumulatively review the relevant data, as available. Minutes will be taken at each meeting, 
and all decisions made during teleconferences will be documented in writing. The sponsor or 
designee is responsible for notifying all study centers of any decisions made during SAC 
meetings.  
The SAC will meet at least quarterly. In addition, the SAC will meet before opening each new 
MAD cohort for enrollment in Phase I. 
Further information on the roles and responsibilities of the SAC can be found in the SAC 
Charter. 
6.6. Product Complaint Handling 
The sponsor collects product complaints on IMPs used in clinical trials in order to ensure the 
safety of study participants, to monitor quality, and to facilitate process and product 
improvements. 
Product complaints related to concomitant drugs are reported directly to the manufacturers of 
those drugs in accordance with the package insert. 
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Patients will be instructed to contact the investigator as soon as possible if they have a product 
complaint or problem with the IMP so that the situation can be assessed. 
The investigator or his/her designee is responsible for handling the following aspects of the 
product complaint process in accordance with the instructions provided for this study: 
•
Recording a complete description of the product complaint reported and any associated
AEs using the study-specific product complaint form provided for this purpose, and
•
Faxing the completed product complaint form within 24 hours to the sponsor or its
designee.
The investigator, when asked to return the product for investigation, will return a copy of the 
product complaint form with the product. 
6.7. Efficacy Evaluations 
6.7.1. Radiographic Tumor Assessment 
Tumor response will be assessed by a radiologist following the RECIST guidelines v. 1.1 
(Appendix 10).9 The schedule of tumor assessments will be maintained independent of any 
treatment schedule delays or changes. For any patient who discontinues the study for reasons 
other than radiographic progression (e.g., symptomatic progression, unacceptable toxicity), a 
tumor assessment will be performed at the Discontinuation visit only if ≥4 weeks has elapsed 
since the last tumor assessment. An unscheduled tumor assessment will be obtained in such 
patients if a Discontinuation visit will not be conducted. Patients who discontinue the study for 
reasons other than radiographic progression will be followed according to standard of care 
following discontinuation.  
6.7.2. Overall Survival 
Overall survival (OS) will be monitored from the time of patient enrollment until the patient is 
lost to follow-up, deceased, the study is considered complete, or a maximum of 1 year is 
reached. The patient’s medical record will be consulted approximately every 3 months to assess 
survival. 
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7. DATA MANAGEMENT METHODS 
7.1. Data Quality Assurance 
To confirm study compliance with the protocol, ICH GCP, and applicable regulatory 
requirements, the study may be audited, inspected, and/or monitored. The investigator will 
permit access to study-related documentation and study facilities for regulatory authorities, 
monitors, auditors, and members of the IEC/IRB for this purpose, provided patient 
confidentiality is maintained. 
To ensure accurate, complete, and reliable data, the sponsor or its representatives will do the 
following: 
• Provide instructional material to the study centers, as appropriate. 
• Sponsor a start-up training session for the investigators and study coordinators on the 
protocol, data entry procedures, and study procedures. 
• Make periodic visits to the study center(s). 
• Be available for consultation and in contact with the study center(s) by mail, telephone, 
email, and/or fax. 
• Review study data, documents and/or procedures for legibility, compliance, 
completeness, accuracy, consistency, and/or timeliness. 
• Discuss the conduct and progress of the study with the investigator and study center 
personnel. 
• Ask the investigator or designee to clarify or complete data discrepancies. 
• Conduct a quality review of the database. 
• Verify the quality of the data. 
The study center may be audited by government regulatory authorities. The investigator will 
notify the sponsor in advance of any scheduled regulatory inspection, and within 24 hours of 
any unscheduled inspection. During an audit, the investigator and study center personnel will 
cooperate fully and provide access to all study facilities, data and documentation. Any 
regulatory inspection records will be forwarded to the sponsor promptly. 
7.2. Direct Data Entry and Computerized Systems 
In this protocol, the term electronic case report form (eCRF) refers to an electronic record of 
study related- data for an individual patient. An eCRF is required and will be completed for each 
patient screened in this clinical study. Data will be captured on eCRFs using an electronic data 
capture (EDC) system, both of which will comply with Title 21 CFR Part 11. The documentation 
related to validation of the EDC system will be retained by the EDC system vendor, and 
validation of the study-specific eCRFs will be conducted and maintained by the sponsor.  
Data collected on the eCRFs will be stored electronically by the EDC vendor on an externally 
hosted server. Any other data stored by a vendor (i.e., the results of laboratory testing or ECG 
data) will be stored electronically on an externally hosted server, and subsequently transferred 
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The term source document refers to any original document, data or record containing patient-
related information. This may include hospital records, clinical and office charts, laboratory 
data/information, patient diaries or evaluation checklists, pharmacy dispensing and other 
records, recorded data from automated instruments, microfiches, photographic negatives, 
microfilm or magnetic media, x-rays, etc. Data collected during this study must be recorded on 
the appropriate source documents. The main source document for this study is the patient’s 
medical record. The information collected on the patient’s eCRF must match this medical 
record.  
It is the responsibility of the investigator to ensure that eCRFs and source documents are 
complete and accurate. The investigator will confirm the authenticity of all laboratory and 
clinical data recorded in the eCRFs by written or electronic signature.  
7.3. Record Retention 
To permit audits by regulatory authorities or the sponsor, the investigator will retain all study-
related documentation. This may include patient records, original signed ICDs, SAE forms, 
source data, source documents, the study protocol, monitoring visit reports, and sufficient 
information to identify participating patients. The sponsor will archive data from EDC that 
pertains to a study center (e.g., patients’ final eCRFs) in a durable media format and forward it 
to the investigator. The records will be retained by the investigator in accordance with the 
regulatory guidelines. 
No study document will be destroyed without prior written agreement from the sponsor, even 
after the minimum retention period has elapsed. 

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8. PHARMACOKINETIC, PHARMACODYNAMIC, SAFETY, AND EFFICACY DATA ANALYSES 
8.1. Data Analysis Plans 
8.1.1. General Considerations 
A detailed statistical analysis plan (SAP) will be developed prior to study completion and 
database lock, which will describe the endpoints and analyses for the study. Any deviations 
from the statistical analyses planned in this protocol or the SAP will be described in the clinical 
study report. 
The administration of IMP, dose interruptions, and dose modifications will be listed with the 
associated reasons. Concomitant medications will be listed by patient with reason for use, dose, 
route, and date of administration at a minimum, and time of administration if available. Major 
protocol deviations will be listed by patient and by study center.  
Safety analyses will be performed on the Full Analysis Set (all patients who receive at least 1 
dose of IMP, whether or not they complete all protocol requirements).  
PK analyses will include all patients who receive at least 1 dose of IMP and have PK data that is 
sufficient and interpretable, as determined by the sponsor.  
PD analyses for target engagement will include all patients who receive at least 1 cycle of IMP 
and from whom samples are collected of sufficient quantity and quality for evaluation. PD 
analyses for hematological changes will include all patients who receive at least 1 dose of IMP 
and have PD data that is sufficient and interpretable, as determined by the sponsor. 
ORR will be assessed in the Full Analysis Set as well as in all patients evaluable for efficacy (all 
patients who complete at least 1 cycle of IMP with adequate compliance [as described in 
Section 8.5.1], and had a tumor assessment by RECIST v1.1 at baseline and at least once 
following receipt of IMP). Subsequent analyses of efficacy may be limited to patients evaluable 
for efficacy. 
Analysis of tumor molecular profile will include all patients who complete at least 1 cycle of AK-
01, and have blood and pre-treatment tumor samples of sufficient quality and quantity to 
permit evaluation using next-generation sequencing or other technology. Comparisons of 
efficacy in patients with specific molecular profiles will include all patients who are evaluable 
for both efficacy and molecular profile, as described above.  
8.1.2. Study Participants  
All patients who discontinue the study will be identified, and the extent of their participation in 
the study will be reported. A reason for their discontinuation will be provided. 
8.1.3. Pharmacokinetic and Pharmacodynamic Analyses 
PK parameters for AK-01 will be computed by standard non-compartmental methods of 
analysis. The primary PK parameters are AUC0-12, AUC0-24, Cmax and the time to reach maximum 
plasma concentration (tmax). Other PK parameters, such as apparent terminal elimination half-

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life (t1/2), CL/F, and apparent volume of distribution (Vz/F) will also be calculated. PK parameters 
will be calculated individually and presented with summary statistics. 
PD analyses may compare hematological changes between time points, as well as target 
engagement across time points, and between tissues.  
PD results may be presented by patient, in summary tables and graphically. 
The relationship between AK-01 PK and PD measures may be evaluated. Modeling may be 
applied. 
8.1.4. Safety Analysis 
All safety data will be listed and tabulated separately for Phase I and II, and analyzed by 
descriptive statistics. 
The results of all scheduled and unscheduled safety assessments will be listed for each patient, 
with the investigator’s assessment of clinical significance. Abnormal results will be listed 
separately, with clinically significant results flagged.  
All AEs will be coded to the appropriate terminology and graded using NCI CTCAE version 4.03. 
AEs may be summarized by cohort with respect to relatedness to AK-01, outcome, seriousness, 
severity, action taken, and date and time of onset and resolution. SAEs, DLTs, DLT-equivalent 
toxicities, and AEs leading to premature withdrawal or death may be summarized. The type of 
toxicities which are dose-limiting may be explored. Values for ECG parameters and change from 
baseline may be listed and summarized using descriptive statistics.  The relationship between 
ECG parameters and AK-01 exposure may be explored. 
8.1.5. Treatment Compliance 
The investigator or designee will verify that IMP supplies are received intact and in the correct 
amounts. Records of receipt, storage, loss, and dispensing of IMP to each patient will be kept. 
The study center will also keep a current and accurate inventory of IMP. Overall accountability 
of the IMP will be performed by the monitor throughout the study and at the close-out visit.  
To confirm treatment compliance, patients must return all AK-01 bottles (empty, partially 
empty, or full) to the study center as indicated by the schedule in  Appendix 1. Study center 
staff will document the bottles returned and the number of capsules per bottle in source 
documents.  
A patient will be considered compliant with respect to treatment if ≤12% and ≥8% of the 
assigned dose is taken. Non-compliance in Cycle 1 of Phase I will result in withdrawal of the 
patient from the study and exclusion of the patient from analysis. Non-compliance in Cycles ≥2 
in Phase I or in Phase II may merit counseling of the patient by the investigator or designee 
about the importance of study treatment compliance. With continued non-compliance, the 
investigator may consider withdrawing the patient. 
Exploratory analysis of the impact of compliance on selected endpoints may be performed if 
deemed necessary. 
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8.1.6. Efficacy Analysis 
The primary assessment of efficacy in Phase II will be based on the ORR, which will be 
compared to 5% using a test of a single proportion.  RECIST v.1.1 criteria will be used to 
determine the effect of AK-01 on tumor burden. ORR, duration of objective response, best 
response on study, progression-free survival, overall survival, and disease control rate may be 
summarized with descriptive statistics. The rate of disease control (stable disease, partial 
response, or complete response assessed by RECIST v. 1.1 in 2 consecutive scans) may be 
summarized by tumor type, as appropriate. Descriptive statistics will be used to analyze all 
tabulated efficacy data. Progression-free survival (PFS) and OS curves may be estimated using 
Kaplan-Meier methods. 
8.1.7. Molecular Profile Analysis 
Bioinformatics analyses may explore molecular profiles predictive of response or resistance to 
AK-01. 
Measures of efficacy (as described in Section 8.1.6) for patients with different molecular 
profiles may be presented by patient, tumor type, and mutation, and in summary tables with 
descriptive statistics. 
8.2. Missing Data 
In general, data imputation to accommodate missing data will not be performed. Patients who 
are not evaluable for PFS and OS will be considered censored at time zero. PFS will be censored 
at the time of last tumor assessment for patients lost to follow-up or who do not experience 
disease progression or death during the study. OS will be censored at the time of last contact 
for patients who are alive at study completion or who are lost to follow-up. For safety data, if 
the causality of an AE is unknown, it will be assumed there was a reasonable possibility the 
event was related to IMP.  
8.3. Interim Data Analysis 
Safety and other available data will be evaluated prior to dose escalation in Phase I as detailed 
in Section 3.1.3. In Phase II, once all patients within a cohort have completed at least 8 cycles of 
treatment, had disease progression, or discontinued IMP, data analyses for that cohort may be 
performed.  
No formal interim data analysis is planned for this study. 

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9. INFORMED CONSENT, ETHICAL REVIEW, AND REGULATORY CONSIDERATIONS 
9.1. Informed Consent 
Before any study-related screening procedures are undertaken and before any prohibited 
medications are withheld from the patient, patients will be given an IEC/IRB-approved ICD 
describing the study. The investigator or designee must ensure that each patient is informed of 
the goals, methods, expected benefits, and potential risks associated with participation in the 
study. Each patient must also be informed that participation is voluntary, and that they may 
withdraw from the study at any time. If the patient decides to participate, the ICD will be signed 
and dated by the patient, the person who obtained informed consent, and any other 
signatories required by local guidelines.  
9.2. Ethical Review 
Prior to study initiation, the investigator at each study center must obtain approval from the 
IEC/IRB for the protocol, protocol changes, Investigator’s Brochure, ICDs, and any other 
relevant documents (e.g., advertisements). The investigator will retain all written 
correspondence with the IEC/IRB. 
During the study, the investigator will promptly notify the IEC/IRB of any changes that affect the 
conduct of the study and/or increase the risk to patients. SAEs and major protocol deviations 
that meet local reporting criteria will be communicated to the IEC/IRB as required. The IEC/IRB 
will be informed of any changes to the ICD or any other documents that had previously been 
approved, and may request their re-approval. The IEC/IRB will also be notified of study 
termination or completion. 
9.3. Regulatory Considerations 
The study will be performed in accordance with the protocol, ICH guidances, the ethical 
principles of the Declaration of Helsinki, and all applicable local regulatory requirements and 
laws. 
9.4. Protocol Compliance 
The clinical study will be conducted as described in the protocol. 
Changes to the protocol will be approved by the sponsor and the IEC/IRB prior to 
implementation, unless the changes are necessary to eliminate immediate hazards to patients. 
In such a case, the investigator must notify the IEC/IRB in writing. 
If changes to the protocol affect patients’ informed consent (i.e., significant changes in study 
design or the risk associated with participation in the study), the ICD will be revised and 
resubmitted to the IEC/IRB. Once approved, the revised ICD must be signed by all new patients 
as well as all registered patients affected by the changes. 

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9.5. Confidentiality of Patient Information 
The investigator and designees will maintain the confidentiality of patient information 
throughout the study. Patient records or information may be viewed by monitors, auditors, 
IEC/IRB members, and regulatory authority representatives in order to review clinical study 
procedures and/or data, provided that patient confidentiality is maintained. Patient names or 
any identifiable variable will not be included in any reports, publications, or communications 
with the sponsor. 
As this study involves sequencing of patient DNA, mutations in the genome of participating 
patients may be identified. All sequencing data collected in the course of this study will be 
anonymized and kept strictly confidential. Neither the patient nor the investigator will be 
notified of any DNA mutations identified. Study numbers will be used to correlate DNA results 
with study specific results without identifying any specific patient demographics. 
9.6. Protocol Signatures 
Each Principal Investigator will sign the Principal Investigator protocol agreement (Section 10), 
and forward a copy to the sponsor or designee. 
9.7. Final Report Signature 
For the clinical study report, the investigator who enrolled the most patients will be considered 
the coordinating investigator. If this is not possible, the sponsor will select the coordinating 
investigator. 
The medical representative of the sponsor will sign the clinical study report to indicate that, to 
the best of his or her knowledge, the report accurately describes the conduct and results of the 
study.

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REFERENCES 
1. 
Bavetsias V, Linardopoulos S. Aurora Kinase Inhibitors: Current Status and Outlook. 
Front Oncol 2015;5:278. 
2. 
Yan M, Wang C, He B, et al. Aurora-A Kinase: A Potent Oncogene and Target for Cancer 
Therapy. Med Res Rev 2016;36:1036-79. 
3. 
Anand S, Penrhyn-Lowe S, Venkitaraman AR. AURORA-A amplification overrides the 
mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell 2003;3:51-62. 
4. 
Wu CC, Yu CT, Chang GC, Lai JM, Hsu SL. Aurora-A promotes gefitinib resistance via a NF-
kappaB signaling pathway in p53 knockdown lung cancer cells. Biochem Biophys Res Commun 
2011;405:168-72. 
5. 
Yang H, He L, Kruk P, Nicosia SV, Cheng JQ. Aurora-A induces cell survival and 
chemoresistance by activation of Akt through a p53-dependent manner in ovarian cancer cells. 
Int J Cancer 2006;119:2304-12. 
6. 
Dar AA, Goff LW, Majid S, Berlin J, El-Rifai W. Aurora kinase inhibitors--rising stars in 
cancer therapeutics? Mol Cancer Ther 2010;9:268-78. 
7. 
Kaye AD, Volpi-Abadie J, Bensler JM, Kaye AM, Diaz JH. QT interval abnormalities: risk 
factors and perioperative management in long QT syndromes and Torsades de Pointes. J Anesth 
2013;27:575-87. 
8. 
Le Tourneau C, Lee JJ, Siu LL. Dose escalation methods in phase I cancer clinical trials. J 
Natl Cancer Inst 2009;101:708-20. 
9. 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid 
tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47. 
10. 
Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration 
rate. Annals of internal medicine 2009;150:604-12. 
11. 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol 1982;5:649-55. 
12. 
New York Heart Association Criteria Committee. Nomenclature and criteria for diagnosis 
of diseases of the heart and great vessels. 9th ed. Boston, MA: Lippincott Williams and Wilkins; 
1994. 
13. 
Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal 
growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College 
of American Pathologists clinical practice guideline update. J Clin Oncol 2013;31:3997-4013. 
14. 
Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical 
Oncology/College Of American Pathologists guideline recommendations for 
immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin 
Oncol 2010;28:2784-95. 

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APPENDICES 
 

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Appendix 1.  Schedule of Events (Phase II) 
 
Screeninga 
Cycle 1 
Cycle 2 
Cycles ≥3s 
Discontinuationt 
30-Day 
Follow-upv 
Q 3 Months 
Follow-up 
Day      
≤28 
1b 
2 
8 
15 
1 
8 
15 
1 
15 
 
 
 
 
V1 
V2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Enrollmentc 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographicsd 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and oncology historye 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight and heightf 
X 
 
X 
 
 
 
X 
 
 
X 
 
X 
 
 
Pregnancy testg 
X 
 
X 
 
 
 
X 
 
 
X 
 
X 
 
 
FSH and estradiolh 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor biopsyi 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
Blood sample for molecular 
profile 
 
 
X 
 
 
 
X 
 
 
X 
 
X 
 
 
Physical examj 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital Signsk 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
12-Lead ECGl 
X 
 
X 
 
 
X 
X 
 
X 
X 
X 
X 
 
 
ECOG performance statusm 
X 
 
X 
 
 
 
X 
 
 
X 
 
X 
X 
 
Hematologyn 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Clinical chemistryo 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis 
X 
 
X 
 
 
 
X 
 
 
X 
 
X 
 
 
Concomitant medication review 
X 
 
X 
 
X 
X 
X 
 
 
X 
 
X 
X 
 
AK-01 dosingp 
 
 
X 
 
 
 
X 
 
 
X 
 
 
 
 
PK samplingq 
 
 
X 
X 
X 
X 
 
 
 
 
 
X 
 
 
AK-01 compliance 
 
 
 
 
X 
X 
X 
 
 
X 
 
X 
 
 
AE monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Radiographic tumor assessment 
X 
 
 
 
 
 
 
 
 
Xr 
 
Xu 
 
 
Survival assessment 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xw 
Abbreviations: AE – adverse event; CT – computed tomography; C – cycle; ECG – electrocardiogram; ECOG – Eastern Cooperative Oncology Group; EDC – electronic data capture; 
D – day; FSH – follicle stimulating hormone; hr – hour; ICD – informed consent documents; MRI – magnetic resonance imaging; PK – pharmacokinetic; RECIST – Response 
Evaluable Criteria in Solid Tumors; V – visit; Q 3 months – every 3 months  
 

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a. All screening procedures must be performed within 28 days prior to Cycle 1 Day 1 (C1D1). Patients will undergo preliminary 
screening procedures at Visit 1 (V1) before becoming eligible for pre-treatment tumor biopsy (V2). 
b. Day 1 will be the day of receipt of the first dose of AK-01 in cycle 1, which will be administered in the clinic. Day 1 must be 
confirmed prior to dosing. Each visit in the cycle will occur +/- 2 days from the scheduled date. Procedures scheduled for 
Days 1, 8, and 15 of a cycle may be performed up to 2 days prior to dosing, but not following dosing (with the exception of PK 
sampling and ECG recording, see schedule).  The patient must stay on the cycle schedules despite dose interruptions. 
c. A patient is considered entered in the study from the time the ICD is signed. A unique study number is assigned to each 
patient at this time. Between completion of screening and the first dose of IMP, a dose cohort will be assigned. A patient is 
considered enrolled in the study once a cohort has been assigned. 
d. The sex assigned at birth, birth date (month and year), and race will be recorded for each patient. Historical and current use 
of alcohol and tobacco products will also be recorded. 
e. Medical and oncology history will be reviewed at the Screening visit. This review will include documentation of any clinically 
significant medical condition, the presence and severity of any symptoms/conditions associated with locally advanced or 
metastatic tumors, and detailed oncology history (tumor type, stage of disease at diagnosis, stage of disease at study 
enrollment, duration of malignancy, presence and site of metastatic disease, surgical history, and history of anti-cancer 
therapies).  
f. Patients will wear lightweight clothing and no shoes during weighing. Height will only be measured at the Screening visit. 
g. Female patients capable of childbearing will be required to use 2 birth control methods while on study and for up to 3 
months after IMP discontinuation; sexually active male patients must use a barrier method of contraception (condom) during 
the study and for at least 90 days following the last dose of IMP. For all female patients, the investigator will document 
potential childbearing status. A pregnancy test will be done at screening, and must be negative for enrollment. Subsequently, 
pregnancy tests will be done for all patients of childbearing potential as indicated in the schedule; the results must be 
confirmed negative prior to dosing on Day 1 of each cycle. Pregnancy tests may use serum or urine; any positive urine 
pregnancy result will be confirmed with a serum pregnancy test. Any female patient or female partner of a male patient 
participating in this study must inform the investigator immediately if pregnancy is suspected. Pregnancy testing is not 
required after the Screening visit for female patients without childbearing potential (documented history of tubal ligation, 
bilateral oophorectomy or hysterectomy, or post-menopausal for at least 1 year with confirmatory FSH and estradiol results). 
h. For women who are post-menopausal, a confirmatory test of serum FSH and estradiol levels will be done at screening. 
i. In Phase II, collection of a pre-treatment tumor biopsy (or archived tissue, as described above) is mandatory for all patients 
(SCLC patients tumor biopsies will be required unless the primary or metastatic tumor site is inaccessible or a quality biopsy 

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cannot be obtained).  Anticoagulants, antiplatelets, and nonsteroidal anti-inflammatory drugs should be stopped prior to 
tumor biopsy according to institutional practice. 
j.
Following the first administration of AK-01, the physical exam will be symptom-directed and at the discretion of the
investigator. After ICD signature, any clinically significant change in physical exam from baseline will be recorded as an AE.
k. Vital sign assessments will include sitting blood pressure, pulse and body temperature. Additional vital sign assessments
may be performed as clinically indicated. For visits in which both vital signs and blood samples are collected, vital signs will
be obtained prior to blood collection. Any clinically significant result of vital sign assessment will be documented as an AE.
l.
Each ECG will be a triplicate assessment.  In Cycle 1, ECGs will be performed at the following time points relative to the first
dose on Day 1 and Day 15: 0 hours (pre-dose) and 1, 2, 4, 6, and 8-12 hours post-dose. ECGs will be performed predose on
Day 1 and Day 15 in subsequent cycles.  An ECG will also be performed prior to any intrapatient dose escalation, and at any
point the investigator considers it is clinically indicated. For visits in which both ECG and vital signs are collected, vital signs
will be measured prior to ECG.  An ECHO evaluation may be performed if clinically indicated.
m. ECOG status will be assessed according to the criteria in Appendix 4.
n. Refer to Appendix 2 for a list of hematology assessments. Additional hematology assessments may be conducted if deemed
necessary by the investigator
o. Refer to  Appendix 2 for a list of clinical chemistry assessments. Additional clinical chemistry assessments may be conducted
if deemed necessary by the investigator
p. Patients will be dispensed AK-01 capsules on Day 1 for all cycles of Phase II. AK-01 may be dispensed up to 2 days prior to
each scheduled dispensing day to facilitate patient scheduling. All assessments on the day of dosing will be performed prior
to the first administration of AK-01, unless noted otherwise. Patient safety and toxicity will be evaluated prior to each dose,
and patients will only be dosed if the results of safety assessments are deemed acceptable by the investigator. AK-01 will be
taken orally twice daily approximately 12 hours apart (see Section 5.2). Patients will be encouraged to fast for 1 hour prior
and following AK-01 dosing. Patients will self-administer the dose when not in the clinic, but on scheduled visit days the first
dose of the day will be administered in the clinic after study procedures are completed. Patients will be dosed in cycles of 21
days at the dose assigned by the sponsor, unless the dose has been reduced for toxicity. Delays in the administration of
AK-01 will be managed by the investigator on a case-by-case basis.
q. PK sampling will be performed in Cycle 1 of both Phase I and II at the following time points relative to the first dose on Day 1
and Day 15: 0 hours (pre-dose) and 1, 2, 4, 6, and 8-12 hours post-dose. Additional trough samples will be obtained prior to
dosing on Day 2 and Day 8 of Cycle 1. The sampling schedule may be modified following review of PK data from the first
cohort in Phase I to optimize collection times. A PK sample will also be obtained at the Discontinuation visit. A maximum of 3

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additional PK samples may be drawn at other time points during the study, if warranted and agreed upon by both the 
investigator and the sponsor.  
r.
A CT scan with IV contrast and assessment of tumor response by RECIST (v. 1.1, see Appendix 10) will occur within 1 week of 
the last dose of Cycle 2 and Cycle 4, and every 9 weeks (± 1 week) thereafter for the duration of treatment. The schedule of 
tumor assessments will be maintained independent of any treatment schedule delays or changes. All CT scans will include 
the chest, abdomen and pelvis. For each tumor assessment, the date, method, and response evaluation will be recorded. 
Tumor response will not be evaluated at the screening CT scan (collected as the baseline). MRI may be performed instead of 
CT if a patient cannot tolerate CT contrast agents due to an iodine allergy. An individual patient will be monitored by the 
same methodology throughout the study. For patients that meet RECIST criteria for complete response or partial response, 
a confirmatory radiographic assessment will be obtained 4 weeks (+/- 5 days) after the response criteria was met.
s.
Dosing of AK-01 may continue until disease progression if the patient is receiving benefit and is experiencing no severe 
toxicity in the opinion of the investigator. Following Cycle 1, an entire cycle may be delayed or advanced by +/-1 day for 
administrative reasons, in which case it will be shortened (or lengthened) by 1 day, respectively.
t.
The discontinuation date will be recorded with the primary reason for discontinuation (if applicable). The patient will attend 
a Discontinuation visit as soon as possible after participation ceases.
u. A CT scan and assessment of tumor response will be performed at the Discontinuation visit for patients who discontinue the 
study for reasons other than radiographic progression, and if a CT scan has not been performed within the prior 4 weeks.
v. Patients will attend a follow-up visit 30 days (+/- 7 days) following the last dose of IMP.
w. Patient survival will be confirmed approximately every 3 months for up to 1 year. 

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Appendix 2. Clinical Laboratory Tests 
 
Clinical Chemistry 
Serum concentrations of: 
• Sodium 
• Potassium 
• Chloride 
• Bicarbonate 
• Total bilirubin 
• Direct bilirubin 
• Gamma-glutamyl transferase 
• Aspartate aminotransferase 
• Alanine aminotransferase 
• Alkaline phosphatase 
• Creatine kinase 
• Lactate dehydrogenase 
• Blood urea nitrogen 
• Creatininea 
• Uric acid 
• Calcium 
• Glucose, random 
• Albumin 
• Total protein 
• Magnesium 
• eGFR 
 
Endocrinology (females only) 
• Urine pregnancy test (human chorionic 
gonadotropin) 
• Serum pregnancy test (human chorionic 
gonadotropin)b 
• Follicle stimulating hormone (post-
menopausal females only) 
• Estradiol (post-menopausal females only) 
Hematology 
• Hemoglobin 
• Hematocrit 
• Red Blood Cell count 
• Reticulocytes 
• Mean cell volume 
• Platelets 
• White blood cell count 
• Neutrophils, segmented 
and banded 
• Mean cell hemoglobin 
concentration 
• Monocytes 
• Eosinophils 
• Basophils 
• Lymphocytes 
 
Urinalysis 
• Color 
• Specific gravity 
• pH 
• Protein 
• Blood 
• Glucose 
• Ketones 
 
a Creatinine must be measured with a method traceable to isotope dilution mass spectrometry (IDBS) 
b Only measured at screening or if a urine pregnancy test is positive 
 
 

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Appendix 3. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation10 
At all study sites, the CKD-EPI equation must be used to calculate eGFR as follows: 
  GFR = 141 × min (Scr/κ, 1)α × max(Scr/κ, 1)-1.209 × 0.993age × 1.018 [if female] × 1.159 [if black]  
 
where: 
Scr is serum creatinine in µmol/L 
κ is 61.9 for females and 79.6 for males 
α is -0.329 for females and -0.411 for males 
min indicates the minimum of Scr /κ or 1 
and max indicates the maximum of Scr /κ or 1 
 
 
 

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Appendix 4. Eastern Cooperative Oncology Group (ECOG) Performance Status11 
Grade 
Description 
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 self-care but unable to carry out 
any work activities. Up and about more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more 
than 50% of waking hours 
4 
Completely disabled. Cannot carry on any self-care. Totally 
confined to bed or chair 
5 
Dead 
 
 

A U R A -0 0 1  
1 0/ A pr/ 2 0 1 8  
Cli nic al St u d y Pr ot oc ol  
V ersi o n 4   
 
 
A ur K a P h ar m a, I nc. — C o nfi d e nti al  
P a g e 5 9  of 9 9  
 
A p p e n di x  5.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C CI
C CI

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Appendix 6. Medications Known to Cause Prolongation of the QT Interval or Torsades de 
Pointes7 
For the most current list of medications, refer to:  https://crediblemeds.org/ (free 
registration required). 
All medications listed in the table are a known risk of TdP and are prohibited while on study.  
This list is not considered comprehensive and the Crediblemeds site should be referenced for 
the most up to date listing.   
Class 
Medication 
Anesthetics 
Propofol 
Sevoflurane 
Antiarrhythmics 
Amiodarone 
Disopyramide 
Dofetilide 
Dronedarone 
Flecainide 
Ibutilide 
Procainamide 
Quinidine 
Sotalol 
Other cardiac drugs 
Bepridil 
Antineoplastic Agent 
Oxaliplatin 
Antipsychotics 
Chlorpromazine 
Haloperidol 
Levomepromazine 
Levosulpiride 
Mesoridazine 
Pimozide 
Sulpiride 
Sultopride 
Thioridazine 
Antibacterials 
Azithromycin 
Ciprofloxacin 
Erythromycin 
Clarithromycin 
Gatifloxacin 
Grepafloxacin 
Levofloxacin 
Moxifloxacin 
Roxithromycin 
Sparfloxacin 
Citalopram 

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Antidepressants 
Escitalopram 
Antifungals 
Fluconazole 
Pentamidine 
Antimalarials 
Chloroquine 
Halofantrine 
Opiates 
Methadone 
Levomethadyl 
Anti-emetics 
Cisapride 
Domperidone 
Droperidol 
Ondansetron 
Antihistamines 
Astemizole 
Terfenadine 
Anti-cancer agents 
Arsenic trioxide 
Vandetanib 
Miscellaneous 
Anagrelide 
Cilostazol 
Cocaine 
Donepezil 
Ibogaine 
Papaverine 
Probucol 
Terlipressin 
Terodiline 
 
 
 

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Appendix 7.  Fridericia Formula for Correction of the QT Interval7 
 
𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄= 𝑄𝑄𝑄𝑄/√𝑅𝑅𝑅𝑅
3
 
 
QTcF = QT interval corrected using the Fridericia formula 
QT = QT interval 
RR = Time between consecutive R waves 
 
 

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Appendix 8. Eligible Breast Cancer Biomarker Expression 
Breast cancer patients will be eligible for Phase II of this study if they meet the criteria for 
biomarker expression given below: 
Biomarker  
Eligible Biomarker Result 
HER2 
0 or 1+ by immunohistochemistry or 
2+ by immunohistochemistry with no evidence of amplification 
by in situ hybridization13 
ER 
≥1% of tumor nuclei positive for ER by 
immunohistochemistry14 
PR 
≥1% of tumor nuclei positive for PR by 
immunohistochemistry14 
Abbreviations: ER – estrogen receptor; HER2 – human epidermal growth factor 
receptor 2; PR – progesterone receptor 
 
 

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Appendix 9.  Common Terminology Criteria for Adverse Events, v. 4.03 
http://evs.nci.nih.gov/ftp1/CTCAECTCAE_4.03_2010-06-14_QuickReference_5x7.pdf 

A U R A -0 0 1  
1 0/ A pr/ 2 0 1 8  
Cli nic al St u d y Pr ot oc ol  
V ersi o n 4   
 
 
A ur K a P h ar m a, I nc. — C o nfi d e nti al  
P a g e 6 5  of 9 9  
 
A p p e n di x  1 0.  
 
 
 
 
 
 
 
 
  
 
   
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C CI
C CI

A U R A -0 0 1  
1 0/ A pr/ 2 0 1 8  
Cli nic al St u d y Pr ot oc ol  
V ersi o n 4   
 
 
A ur K a P h ar m a, I nc. — C o nfi d e nti al  
P a g e 6 6  of 9 9  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
C CI

A U R A -0 0 1  
1 0/ A pr/ 2 0 1 8  
Cli nic al St u d y Pr ot oc ol  
V ersi o n 4   
 
 
A ur K a P h ar m a, I nc. — C o nfi d e nti al  
P a g e 6 7  of 9 9  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C CI

A U R A -0 0 1  
1 0/ A pr/ 2 0 1 8  
Cli nic al St u d y Pr ot oc ol  
V ersi o n 4   
 
 
A ur K a P h ar m a, I nc. — C o nfi d e nti al  
P a g e 6 8  of 9 9  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C CI

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Appendix 12. Summary of Protocol Changes  
 
Protocol Version 2: AURA-001(a), 25/May/2017 
Protocol AURA-001 [A Phase I/II Open-Label Multicenter Study to Evaluate the Safety and 
Efficacy of AK-01 as Monotherapy in Patients with Locally Advanced or Metastatic Solid Tumors] 
has been amended to create Version 2, dated 25/May/2017.  The new protocol is indicated by 
amendment (a) and will be used to conduct the study in place of any preceding version of the 
protocol. 
The overall changes and rationale for the changes made to this protocol are as follows: 
Inclusion/Exclusion Criteria 
• The renal inclusion criteria is updated from ≥60 mL/min/1.73 m2 to ≥45 mL/min/1.73 
m2. 
In humans, elimination of AK-01 is anticipated to occur through oxidative metabolism 
followed by formation of glucuronide conjugates which are then excreted by the kidney. 
Conjugates such as these are typically pharmacologically inactive. Based on nonclinical data, 
approximately 15% of drug-related material was excreted in the urine, while the urinary 
elimination of intact AK-01 was less than 2%.   
 
Since the contribution of renal elimination is predicted to be minimal, diminished renal 
function should not significantly affect overall AK-01 exposure.   
Furthermore, the toxicity profile of AK-01 is monitorable and reversible. Dose escalations 
will be guided by safety, exposure, and PD data (as available) and will only be allowed after 
careful examination of the tolerability data of the dose in the previous cohort. 
 
• Patients must have histological or cytological evidence of a solid tumor that is locally 
advanced and/or metastatic and have failed locally approved therapies that have clinical 
benefit as follows:… 
• Have medical conditions that, in the opinion of the investigator, would preclude 
participation in this study such as overwhelming infections.  
Safety Data Collection and Review 
The additional option of ECHO and ophthalmologic evaluations are added if in the opinion of 
the investigator these should be conducted for patient safety: 
• The investigator may conduct an echocardiogram (ECHO) evaluation if clinically 
indicated. 
• More advanced ophthalmologic exams may be done at the request of the investigator if 
needed. 

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Serious Adverse Events 
The follow sentence was updated to clarify SAE reporting requirements:   
Study center personnel must alert the sponsor or its designee of any serious adverse event 
(SAE) within 24 hours following investigator knowledge of the event via a sponsor-approved 
method.  
 
Schedule of Events (Phase I and Phase II) 
• Physical Exam was added to Cycle 2 Day 8 as this was an oversight.  Physical exams are to be 
at any visit the investigator feels necessary. 
• ECG timing language was added to clarify the instructions for when to conduct multiple 
timepoint ECGs. 
• ECHO evaluation was added if investigator feels this is necessary. 
 
Medications Known to Cause Prolongation of the QT Interval or Torsades de Pointes7 
Table is updated and reference to Crediblemeds has been included. 
 
Contacts 
• Team member contacts were updated. 
 
 

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Revised Protocol Sections 
 
 
4. 
STUDY POPULATION 
4.1. 
Criteria for Enrollment 
Phase II 
17. Patients must have disease that is measurable by RECIST v.1.1 (see Appendix 10). 
18. Patients must have histological or cytological evidence of a solid tumor that is locally 
advanced and/or metastatic and have failed locally approved therapies that have clinical 
benefit as follows: 
a. SCLC 
• Must have failed platinum-containing therapy. 
b. BC 
• ER+ and/or PR+ but HER2-negative (see Appendix 8 for eligible biomarker 
expression). 
• Must have failed a hormone therapy and a CDK4/6 inhibitor. 
c. A solid tumor type that has been approved by the sponsor. 
4.2. 
Exclusion Criteria 
Patients who meet the following criteria will be excluded from the study: 
19. Have medical conditions that, in the opinion of the investigator, would preclude 
participation in this study (e.g., a new or preexisting swallowing disorder that would make 
oral administration difficult).  Such as overwhelming infections.  
20. Have symptomatic central nervous system (CNS) metastasis. Patients with treated CNS 
metastasis are eligible if they are asymptomatic and not currently receiving 
corticosteroids. Screening of asymptomatic patients without a history of CNS metastasis is 
not required. 
21. Have a primary tumor of the CNS. 
22. Have a history of organ transplant (e.g., heart, lungs, liver, bone marrow, or kidney). 
23. Females who are pregnant or nursing. 
24. Have symptomatic human immunodeficiency virus (HIV) infection, known HIV positive 
test results or have chronic active hepatitis B or C (screening is not required). 
25. Have clinically significant cardiac disease including any of the following: 
Note: 
Deletions have been identified by strikethroughs or grayed out for figures. 
Additions have been identified by the use of underscore.  

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• A history of congenital long QT syndrome, symptomatic bradycardia, ventricular 
arrhythmia, uncontrolled atrial fibrillation, second or third degree heart block, or 
other conduction abnormality that in the opinion of the investigator would 
preclude safe participation in this study. 
• Congestive heart failure (New York Heart Association Class ≥3; see Appendix 5). 
• Unstable angina pectoris, acute myocardial infarction, or stroke ≤12 months prior 
to enrollment. 
• QTcF prolongation >450 msec. 
26. Currently taking medication known to prolong the QT interval or induce TdP (see 
Appendix 6) which cannot be discontinued or substituted. 
27. Have >Grade 1 hypokalemia, hypomagnesemia, or hypocalcemia which cannot be 
controlled prior to enrollment. 
28. Have a history of major surgery to the upper gastrointestinal (GI) tract, GI disease or 
other medical condition that in the opinion of the investigator may interfere with oral 
drug absorption. 
29. Are a family member of the investigator or staff of the study site. 
30. Are currently enrolled in another clinical study of an investigational therapy. 
31. Previous therapy with an Aurora kinase inhibitor. 
32. Hypersensitivity to any components of AK-01. 
6. 
PHARMACOKINETIC, PHARMACODYNAMIC, SAFETY AND EFFICACY DATA COLLECTION 
6.5. 
Safety Evaluations 
6.5.1. Safety Measures 
This study contains detailed safety monitoring that will permit characterization of the safety 
profile of AK-01 in patients with locally advanced or metastatic tumors. See Appendix 1 for the 
schedule of safety assessments.  
6.5.2. Safety Data Collection and Review 
The investigator is responsible for the safety of all patients registered in this clinical study.  
For all scheduled and unscheduled safety assessments, the results and investigator’s 
assessment of clinical significance will be recorded (i.e., clinical laboratory evaluations 
[hematology, clinical chemistry, endocrinology, and urinalysis], ECOG status, electrocardiogram 
[ECG], vital signs, and physical exam).  
All ECGs will be 12-lead triplicate assessments obtained using digital equipment approximately 
5 minutes apart at the time points indicated in Appendix 1. For each ECG, the rate, rhythm, 
interval duration, appearance and axis will be recorded (HR, PQ, QRS, QT, RR, T wave and U 
wave). The QT interval will be corrected for heart rate using Fridericia’s formula (Appendix 7). A 
qualified physician will evaluate all ECG results, document the clinical significance on the 
tracing, and sign and date the tracing. The original annotated ECG tracing along with a 
photocopy of the tracing containing the physician's assessment will be retained in the patient's 

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records at the study center. ECGs will be independently reviewed by a central laboratory; 
instructions for the collection and transmission of ECGs to the independent reviewer will be 
provided. Additional ECGs may be obtained if medically warranted. When an ECG is scheduled 
on the same day as a blood collection, the ECG will be obtained prior to blood collection. Any 
clinically significant ECG result will be documented as an AE.  The investigator may conduct an 
echocardiogram (ECHO) evaluation if clinically indicated. 
Clinical laboratory tests are listed in Appendix 2. For all clinical laboratory safety tests, a 
certified local laboratory will be used to perform laboratory analyses to guide treatment 
decisions and data analysis. Qualified medical staff will review, initial and date all laboratory 
results. 
More advanced ophthalmologic exams may be done at the request of the investigator if 
needed. 
An AE will be recorded for the result of any safety assessment (e.g., ECG, vital signs, clinical 
chemistry value, etc.) that requires a patient to be discontinued from the study or receive 
treatment. The medical condition caused by the abnormal result should be recorded, rather 
than the abnormal result (e.g., hyperglycemia instead of elevated glucose). For the result of any 
safety assessment which requires a patient to be discontinued or receive treatment, the 
investigator will follow the AE to a satisfactory clinical resolution. 
6.5.3. Serious Adverse Events 
Study center personnel must alert the sponsor or its designee of any serious adverse event 
(SAE) within 24 hours following of investigator knowledge awareness of the event via a 
sponsor-approved method. Alerts issued via telephone must be immediately followed with 
official notification on study-specific SAE forms. An SAE is any AE from this study that results in 
one of the following outcomes: 
• Death  
• Initial or prolonged inpatient hospitalization 
• A life-threatening experience (that is, immediate risk of dying) 
• Persistent or significant disability/incapacity 
• Congenital anomaly/birth defect 
• Considered significant by the investigator for any other reason. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious adverse drug events 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. Preplanned surgeries will 
not be reported as SAEs, however if an AE occurs during hospitalization for preplanned surgery 
that meets the above criteria, it will be reported as an SAE. SAEs due to progressive disease 
(including death) should not be reported as SAEs unless the investigator also deems there is a 
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All SAEs occurring from the time the patient signs the ICD until the 30-day Follow-up visit must 
be reported to the sponsor or its designee regardless of relatedness to IMP or protocol 
procedures. Thereafter, SAEs will be reported only if the investigator feels the events were 
related to the IMP or a protocol procedure. 
Appendix 1 outlines specific safety assessments for the 30-day Follow-up visit. All drug-related 
AE and SAEs will be followed until the events resolve, the events are no longer considered to be 
drug-related, the patient dies or is lost to follow-up, or until a new treatment is initiated for the 
patient. Frequency of follow-up evaluation is left to the discretion of the investigator.  
The medical representative of the sponsor will monitor safety data throughout the course of 
the study. The sponsor and/or its designee will review SAEs within appropriate timeframes to 
meet reporting obligations imposed by regulatory authorities. All serious and unexpected AEs 
for this study will be reported to regulatory authorities in accordance with local laws, directives 
and regulations. 
 
 

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Appendix 1. 
Schedule of Events (Phase I and Phase II 
 
Screeninga 
Cycle 1 
Cycle 2 
Cycles ≥3t 
Discontinuationu 
30-Day 
Follow-upw 
Q 3 Months 
Follow-up 
Day      
≤28 
1b 
2 
8 
15 
1b 
8 
15 
1 
15 
 
 
 
 
V1 
V2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Enrollmentc 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographicsd 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and oncology historye 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight and heightf 
X 
 
X 
 
 
 
X 
 
 
X 
 
X 
 
 
Pregnancy testg 
X 
 
X 
 
 
 
X 
 
 
X 
 
X 
 
 
FSH and estradiolh 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Skin biopsyi 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
Tumor biopsyj 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
Blood sample for molecular 
profile 
 
 
X 
 
 
 
X 
 
 
X 
 
X 
 
 
Physical examk 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital Signsl 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
12-Lead ECGm 
X 
 
X 
 
 
X 
X 
 
X 
X 
X 
X 
 
 
ECOG performance statusn 
X 
 
X 
 
 
 
X 
 
 
X 
 
X 
X 
 
Hematologyo 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Clinical chemistryp 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis 
X 
 
X 
 
 
 
X 
 
 
X 
 
X 
 
 
Concomitant medication review 
X 
 
X 
 
X 
X 
X 
 
 
X 
 
X 
X 
 
AK-01 dosingq 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
PK samplingr 
 
 
X 
X 
X 
X 
 
 
 
 
 
X 
 
 
AK-01 compliance 
 
 
 
 
X 
X 
X 
 
 
X 
 
X 
 
 
AE monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Radiographic tumor assessment 
X 
 
 
 
 
 
 
 
 
Xs 
 
Xv 
 
 
Survival assessment 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xx 
Abbreviations: AE – adverse event; CT – computed tomography; C – cycle; ECG – electrocardiogram; ECOG – Eastern Cooperative Oncology Group; EDC – electronic data capture; 
D – day; FSH – follicle stimulating hormone; hr – hour; ICD – informed consent documents; MRI – magnetic resonance imaging; PK – pharmacokinetic; RECIST – Response 
Evaluable Criteria in Solid Tumors; V – visit; Q 3 months – every 3 months  
 

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a. All screening procedures must be performed within 28 days prior to Cycle 1 Day 1 (C1D1). Patients will undergo preliminary 
screening procedures at Visit 1 (V1) before becoming eligible for pre-treatment tumor biopsy (V2). 
b. Day 1 will be the day of receipt of the first dose of AK-01 in cycle 1, which will be administered in the clinic. Each visit in the 
cycle will occur +/- 2 days from the scheduled date regardless of dose interruptions. Procedures scheduled for Days 1, 8, and 
15 of a cycle may be performed up to 2 days prior to dosing, but not following dosing (with the exception of PK sampling, see 
schedule).  
c. A patient is considered entered in the study from the time the ICD is signed. A unique study number is assigned to each 
patient at this time. Between completion of screening and the first dose of IMP, a dose cohort will be assigned. A patient is 
considered enrolled in the study once a cohort has been assigned. 
d. The sex assigned at birth, birth date (month and year), and race will be recorded for each patient. Historical and current use 
of alcohol and tobacco products will also be recorded. 
e. Medical and oncology history will be reviewed at the Screening visit. This review will include documentation of any clinically 
significant medical condition, the presence and severity of any symptoms/conditions associated with locally advanced or 
metastatic tumors, and detailed oncology history (tumor type, stage of disease at diagnosis, stage of disease at study 
enrollment, duration of malignancy, presence and site of metastatic disease, surgical history, and history of anti-cancer 
therapies).  
f. Patients will wear lightweight clothing and no shoes during weighing. Height will only be measured at the Screening visit. 
g. Female patients capable of childbearing will be required to use 2 birth control methods while on study and for up to 3 
months after IMP discontinuation; sexually active male patients must use a barrier method of contraception (condom) during 
the study and for at least 90 days following the last dose of IMP. For all female patients, the investigator will document 
potential childbearing status. A pregnancy test will be done at screening, and must be negative for enrollment. Subsequently, 
pregnancy tests will be done for all patients of childbearing potential as indicated in the schedule; the results must be 
confirmed negative prior to dosing on Day 1 of each cycle. Pregnancy tests may use serum or urine; any positive urine 
pregnancy result will be confirmed with a serum pregnancy test. Any female patient or female partner of a male patient 
participating in this study must inform the investigator immediately if pregnancy is suspected. Pregnancy testing is not 
required after the Screening visit for female patients without childbearing potential (documented history of tubal ligation, 
bilateral oophorectomy or hysterectomy, or post-menopausal for at least 1 year with confirmatory FSH and estradiol results). 
h. For women who are post-menopausal, a confirmatory test of serum FSH and estradiol levels will be done at screening. 
i. In Phase I dose escalation and P2D confirmation cohorts, skin biopsy will be required pre-treatment (within 28 days prior to 
C1D1) and on-treatment (C2D8, ±3 days). Both skin biopsies may be scheduled once the patient is confirmed to meet all 
other eligibility criteria and has been assigned a study number. A punch biopsy 2 mm in width will be taken from clinically 

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normal skin; the on-treatment biopsy will be performed 2-6 hrs following the first dose of the day. Prior to opening 
enrollment in Phase II, the sponsor will inform investigators whether skin biopsies are required in Phase II.  If required, skin 
biopsies will be collected as described for Phase I. 
j. For all Phase I patients enrolled in the P2D confirmation cohorts, biopsy of primary or metastatic tumor is required pre-
treatment (within 28 days prior to C1D1) and on-treatment (C2D8, ±3 days). Both tumor biopsies will be scheduled once the 
patient is confirmed to meet all other eligibility criteria and has been assigned a study number. If available, archived 
specimen(s) from a diagnostic biopsy and/or surgery collected within 3 months of screening may be requested instead of the 
pre-treatment tumor biopsy as long as the biopsy was obtained after they had already failed previously therapy. The on-treatment tumor 
biopsy will be performed 2-6 hrs following the first dose of the day, preferably on the same day as the skin biopsy, and will be 
taken from the same tumor site (i.e., primary or metastatic) as the pre-treatment sample if possible. In Phase II, collection of 
a pre-treatment tumor biopsy (or archived tissue, as described above) is mandatory for all patients.  Prior to opening 
enrollment in Phase II, the sponsor will inform investigators whether additional tumor biopsies are required.  Anticoagulants, 
antiplatelets, and nonsteroidal anti-inflammatory drugs should be stopped prior to tumor biopsy according to institutional 
practice. 
k. Following the first administration of AK-01, the physical exam will be symptom-directed and at the discretion of the 
investigator. After ICD signature, any clinically significant change in physical exam from baseline will be recorded as an AE. 
l. Vital sign assessments will include sitting blood pressure, pulse and body temperature. Additional vital sign assessments may 
be performed as clinically indicated. For visits in which both vital signs and blood samples are collected, vital signs will be 
obtained prior to blood collection. Any clinically significant result of vital sign assessment will be documented as an AE.  
m. Each ECG will be a triplicate assessment.  In Cycle 1, ECGs will be performed at the following time points relative to the first 
dose on Day 1 and Day 15: 0 hours (pre-dose) and 1, 2, 4, 6, and 8-12 hours post-dose. ECGs will be performed predose on 
Day 1 and Day 15 in subsequent cycles.  An ECG will also be performed prior to any intrapatient dose escalation, and at any 
point the investigator considers it is clinically indicated. For visits in which both ECG and vital signs are collected, vital signs 
will be measured prior to ECG.  An ECHO evaluation may be performed if clinically indicated. 
n. ECOG status will be assessed according to the criteria in Appendix 4. 
o. Refer to Appendix 2 for a list of hematology assessments. Additional hematology assessments may be conducted if deemed 
necessary by the investigator 
p. Refer to Appendix 2 for a list of clinical chemistry assessments. Additional clinical chemistry assessments may be conducted if 
deemed necessary by the investigator 
q. Patients will be dispensed AK-01 capsules as follows: Days 1, 8, and 15 for Cycle 1 of Phase I, Day 1 for Cycles ≥2 of Phase I, 
and Day 1 for all cycles of Phase II. AK-01 may be dispensed up to 2 days prior to each scheduled dispensing day to facilitate 

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patient scheduling. All assessments on the day of dosing will be performed prior to the first administration of AK-01, unless 
noted otherwise. Patient safety and toxicity will be evaluated prior to each dose, and patients will only be dosed if the results 
of safety assessments are deemed acceptable by the investigator. AK-01 will be taken orally twice daily approximately 12 
hours apart (see Section 5.2). Patients will be encouraged to fast for 1 hour prior and following AK-01 dosing. Patients will 
self-administer the dose when not in the clinic, but on scheduled visit days the first dose of the day will be administered in 
the clinic after study procedures are completed. Patients will be dosed in cycles of 21 days at the dose assigned by the 
sponsor, unless the dose has been reduced for toxicity. Delays in the administration of AK-01 will be managed by the 
investigator on a case-by-case basis. 
r. PK sampling will be performed in Cycle 1 of both Phase I and II at the following time points relative to the first dose on Day 1 
and Day 15: 0 hours (pre-dose) and 1, 2, 4, 6, and 8-12 hours post-dose. Additional trough samples will be obtained prior to 
dosing on Day 2 and Day 8 of Cycle 1. The sampling schedule may be modified following review of PK data from the first 
cohort in Phase I to optimize collection times. A PK sample will also be obtained at the Discontinuation visit. A maximum of 3 
additional PK samples may be drawn at other time points during the study, if warranted and agreed upon by both the 
investigator and the sponsor.  
s. A CT scan with IV contrast and assessment of tumor response by RECIST (v. 1.1, see Appendix 10) will occur within 1 week of 
the last dose of Cycle 2 and Cycle 4, and every 9 weeks (± 1 week) thereafter for the duration of treatment. The schedule of 
tumor assessments will be maintained independent of any treatment schedule delays or changes. All CT scans will include 
the chest, abdomen and pelvis. For each tumor assessment, the date, method, and response evaluation will be recorded. 
Tumor response will not be evaluated at the screening CT scan (collected as the baseline). MRI may be performed instead of 
CT if a patient cannot tolerate CT contrast agents due to an iodine allergy. An individual patient will be monitored by the 
same methodology throughout the study. For patients that meet RECIST criteria for complete response or partial response, a 
confirmatory radiographic assessment will be obtained 4 weeks (+/- 5 days) after the response criteria was met. 
t. Dosing of AK-01 may continue until disease progression if the patient is receiving benefit and is experiencing no severe 
toxicity in the opinion of the investigator. Following Cycle 1, an entire cycle may be delayed or advanced by +/-1 day for 
administrative reasons, in which case it will be shortened (or lengthened) by 1 day, respectively. 
u. The discontinuation date will be recorded with the primary reason for discontinuation (if applicable). The patient will attend 
a Discontinuation visit as soon as possible after participation ceases. 
v. A CT scan and assessment of tumor response will be performed at the Discontinuation visit for patients who discontinue the 
study for reasons other than radiographic progression, and if a CT scan has not been performed within the prior 4 weeks. 
w. Patients will attend a follow-up visit 30 days (+/- 7 days) following the last dose of IMP.  
x. Patient survival will be confirmed approximately every 3 months for up to 1 year

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Appendix 6  
Medications Known to Cause Prolongation of the QT Interval or Torsades de 
Pointes7 
For the most current list of medications, refer to:  https://crediblemeds.org/ (free registration 
required). 
All medications listed in the table are a known risk of TdP and are prohibited while on study.  
This list is not considered comprehensive and the Crediblemeds site should be referenced for 
the most up to date listing.   
Class 
Medication 
Anesthetics 
Propofol 
Sevoflurane 
Antiarrhythmics 
Amiodarone 
Disopyramide 
Dofetilide 
Dronedarone 
Flecainide 
Ibutilide 
Procainamide 
Quinidine 
Sotalol 
Other cardiac drugs 
Bepridil 
Antineoplastic Agent 
Oxaliplatin 
Antipsychotics 
Chlorpromazine 
Haloperidol 
Levomepromazine 
Levosulpiride 
Mesoridazine 
Pimozide 
Sulpiride 
Sultopride 
Thioridazine 
Antibacterials 
Azithromycin 
Ciprofloxacin 
Erythromycin 
Clarithromycin 
Gatifloxacin 
Grepafloxacin 
Levofloxacin 
Moxifloxacin 
Roxithromycin 
Sparfloxacin 

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Antidepressants 
Citalopram 
Escitalopram 
Antifungals 
Fluconazole 
Pentamidine 
Antimalarials 
Chloroquine 
Halofantrine 
Opiates 
Methadone 
Levomethadyl 
Anti-emetics 
Cisapride 
Domperidone 
Droperidol 
Ondansetron 
Antihistamines 
Astemizole 
Terfenadine 
Anti-cancer agents 
Arsenic trioxide 
Vandetanib 
Miscellaneous 
Clobutinol 
Anagrelide 
Cilostazol 
Cocaine 
Donepezil 
Ibogaine 
Papaverine 
Probucol 
Terlipressin 
Terodiline 
 
 
 
 

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Protocol Version 3: AURA-001(b), 1/June/2017 
Protocol AURA-001 [A Phase I/II Open-Label Multicenter Study to Evaluate the Safety and 
Efficacy of AK-01 as Monotherapy in Patients with Locally Advanced or Metastatic Solid Tumors] 
has been amended to create Version 3, dated 1/June/2017.  The new protocol is indicated by 
amendment (b) and will be used to conduct the study in place of any preceding version of the 
protocol. 
The overall changes and rationale for the changes made to this protocol are as follows: 
3.4. 
Discussion of Design and Control 
Clarification has been provided to the modified 3+3 statistical design. 
 
Summary of Protocol Changes 
Inclusion/Exclusion Criteria Rational for the renal inclusion criteria is updated. 
 
 
 

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Revised Protocol Sections 
 
 
3.4. 
Discussion of Design and Control 
Phase I is a dose escalation study with a modified 3 + 3 design. The 3+3 design is modified to 
allow expansion of a cohort with 3 additional patients if 1 DLT is observed in 6 patients for a 
total of 9 patients in the cohort (see Figure 2).  The rules-based 3 + 3 method for dose 
escalation is well-established, safe, and does not require real-time PK or computational 
modeling.8 Intrapatient dose escalation is permitted to allow each patient to potentially receive 
a maximum tolerated dose of AK-01 (see Section 3.1.4). In Phase II, preliminary efficacy of AK-
01 will be assessed in up to 3 cohorts (BC, SCLC, and/or one other solid tumor of interest). 
Preclinical evidence indicates AK-01 may be particularly efficacious in these tumor types. 
Since this is not a comparison study, the use of a placebo control is not applicable. 
 
Summary of Protocol Changes 
Inclusion/Exclusion Criteria 
• The renal inclusion criteria is updated from ≥60 mL/min/1.73 m2 to ≥45 mL/min/1.73 
m2. 
In humans, elimination of AK-01 is anticipated to occur through oxidative metabolism 
followed by formation of glucuronide conjugates which are then excreted by the kidney. 
Conjugates such as these are typically pharmacologically inactive. Based on nonclinical data, 
approximately 15% of drug-related material was excreted in the urine, while the urinary 
elimination of intact AK-01 was less than 2%.   
 
Since the contribution of renal elimination is predicted to be minimal, diminished renal 
function should not significantly affect overall AK-01 exposure.   
Furthermore, the toxicity profile of AK-01 is monitorable and reversible. Dose escalations 
will be guided by safety, exposure, and PD data (as available) and will only be allowed after 
careful examination of the tolerability data of the dose in the previous cohort. 
 
In humans, excretion of AK-01 is anticipated to occur through metabolism followed by renal 
excretion, based on dog and monkey data that indicate that the urinary excretion of AK-01 
Note: 
Deletions have been identified by strikethroughs or grayed out for figures. 
Additions have been identified by the use of underscore.  

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is likely to be insignificant (less than 2%).  In addition, 19F-NMR data indicated that the 
amount of drug-related material excreted from urine was 15% of dose after oral dosing.   
Slow clearance was determined in preclinical species (5.5-37% of hepatic blood flow) 
with bile excretion and metabolism as the major clearance pathways.  Acyl 
glucuronidation and oxidative metabolism were major metabolism pathways.  
Glutathione conjugates were found in rodent hepatocytes, rat bile and urine and 
monkey feces, but not in human liver hepatocytes. No metabolites were observed in 
incubations with human recombinant P450s (rCYPs) and human liver microsome CYP 
fingerprinting assays, thus, the CYP isoform(s) responsible for LSN3295668 metabolism 
could not be identified.  
 
Since the contribution of urinary excretion to the metabolism and excretion of AK-01 is 
predicted to be minimal, a diminished renal function should not significantly affect 
overall exposure.   
Furthermore, the toxicity profile of AK-01 is monitorable and reversible. Dose escalations 
will be guided by safety, exposure, and PD data (as available) and will only be allowed after 
careful examination of the tolerability data of the dose in the previous cohort. 
 
 
 
 

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Protocol Version 4: AURA-001(c), 10/Apr/2018 
Protocol AURA-001 [A Phase I/II Open-Label Multicenter Study to Evaluate the Safety and 
Efficacy of AK-01 as Monotherapy in Patients with Locally Advanced or Metastatic Solid Tumors] 
has been amended to create Version 4, dated 10/Apr/2018.  The new protocol is indicated by 
amendment (c) and will be used to conduct the study in place of any preceding version of the 
protocol. 
The overall changes and rationale for the changes made to this protocol are as follows: 
• Data from the ongoing Phase I added  
• A 25 mg BID was selected as the Phase II dose. This has been added as appropriate. 
• Phase II population has been revised as below and included at all relevant places in the 
protocol: 
o Initially patients with SCLC and HER-2 negative BC will be enrolled in 2 cohorts. 
Subsequentlly, at sponsor’s discretion, patients will following tumor types may 
be enrolled in additional 2 cohorts: triple negative breast cancer, squamous cell 
cancers of the head neck that are HPV+ and have failed standard therapy, and/or 
any other tumor type that warrants further exploration. 
• Additional information were added to the inclusion criteria for all cancer/tumor types. 
• Sample size of Phase II was revised from 80 patients to 120 patients overall 
(≤30 patients in each of 4 cohorts). 
• A clarification added that all study sites will use the same formula for calculation of 
eGFR. 
 
 

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Revised Protocol Sections 
 
 
1.2.  
Rationale and Justification for the Study 
Preclinical data demonstrating biologic activity in vivo with an acceptable safety profile 
supports the evaluation of AK-01 in humans.  
The selectivity of AK-01 for AurA differentiates AK-01 from other inhibitors of Aurora kinases 
(e.g., MLN8237, AZD1152, and PHA-739358),1 and may allow AK-01 to elicit the benefits of 
AurA inhibition without triggering the adverse and often dose-limiting neutropenia associated 
with AurB inhibition.   
The present study will evaluate the safety and efficacy of AK-01 in patients with locally 
advanced or metastatic solid tumors, with an emphasis on small-cell lung cancer (SCLC), 
estrogen receptor (ER+) and/or progesterone receptor (PR+) positive/HER2-negative breast 
cancer (BC), triple negative- breast cancer (TNBC), human papilloma virus (HPV) associated 
squamous cell cancers of the head neck, and any other indication that warrants further 
exploration.  A large proportion of SCLC and hormone-positive BCthese patients bear a Rb1 
loss-of function mutation, a molecular signature which sensitized animal models to AK-01 in 
preclinical testing (see Investigator’s Brochure). Patients are eligible for the Phase II part of this 
study if they have failed standard of care therapies which do not preclude therapy with an AurA 
inhibitor: hormone therapy and CDK4/6 inhibitor for ER+ and/or PR+ BC, and platinum-
based- therapy for SCLC, relapsed/resistant TNBC, HPV associated squamous cell cancers of the 
head neck, and any other indication that warrants further exploration (see Investigator’s 
Brochure for further details). 
1.3. 
Data from Ongoing Phase I Part of the Study 
A total of 11 patients have been dosed in the ongoing Phase I part of the study since June 2017 
with doses of AK01 of up to 75 mg BID. Dose limiting toxicities (DLTs) were noted at both 75 mg 
and 50 mg dose levels. The 25 mg twice a day (BID) dose has been chosen as the dose for Phase 
II.   
Based on safety analysis of the ongoing Phase I part of the study, the following are considered 
as potential adverse events (AEs): bone marrow toxicity including neutropenia and 
thrombocytopenia; gastrointestinal toxicity including mucositis and diarrhea; and corneal 
deposition with blurry vision and double vision.  Appropriate follow up and rapid therapy for 
any of these events will be undertaken.  
Additional information on the reported AEs is available in the investigator’s brochure (IB).  
 
Note: 
Deletions have been identified by strikethroughs or grayed out for figures. 
Additions have been identified by the use of underscore.  

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2 
STUDY OBJECTIVES 
2.1 
Phase I 
The exploratory objectives are: 
• 
To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of 
AK-01. 
• 
To compare PD markers of AK-01 target engagement in skin and tumor biopsies. 
• 
To assess preliminary evidence of AK-01 anti-tumor activity.  
3. 
INVESTIGATIONAL PLAN 
This open-label, non-randomized, multi-center study will explore the safety, PK, PD, and 
efficacy of AK-01 administered in 21-day cycles to patients with locally advanced or metastatic 
solid tumors.  
In Phase I of this study, patients with locally advanced or metastatic solid tumors (all-comers) 
will be administered AK-01 according to a multiple ascending dose (MAD) schedule to 
determine the MTD.  The phase II dose (P2D) may be confirmed in up to 6 additional patients, 
and may take into consideration the MTD, evidence of AurA and AurB target engagement, and 
PK.  The P2D will not exceed the MTD. Throughout Phase I, safety, tolerability, PK, PD, and early 
evidence of anti-tumor activity will be assessed.  
In Phase II of this study, AK-01 will be administered in up to 34 cohorts: initially in patients with 
SCLC and BC, and subsequently, at the sponsor’s discretion, in patients with one of the 
following: TNBC, HPV associated SCC-HN, and/or any OT that warrants further exploration. BC, 
SCLC, and/or one other solid tumor type.  Specific inclusion/exclusion criteria to support a third 
tumor type will be added to the protocol by amendment.  Efficacy, safety, PK, and PD will be 
assessed.   
An overview of the study design is given in Figure 1. 

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3.1.3. Dose Escalation Rules 
Enrollment cannot begin in a new cohort until the Safety Assessment Committee (SAC, see 
Section 6.5.5) has met to discuss the data from the previous dose level. Safety data will be the 
primary criteria for both the decision to dose escalate and for selecting the dose to be 
administered in the next cohort.  The 25 mg BID dose has been chosen as the dose for Phase II 

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(Section 1.3). Plasma concentration will be reviewed following dosing of the third cohort (200 
mg BID dose suggested) and after occurrence of DLT, without halting enrollment.  Additional PK 
parameters may be evaluated, as available (maximum serum concentration [Cmax], area under 
the AK-01 plasma concentration versus time curve from time zero to 12 hours post-dose [AUC0-
12], and 24 hour post-dose [AUC0-24], and apparent clearance [Cl/F]. If available at the time of 
the SAC review, other PD and/or PK parameter results may be used as supporting data for 
evaluation of dose escalation. 
The dose for the subsequent cohort will be decided by the SAC.  Daily BID doses of 25, 75, 200, 
400, 600, or 800 mg are proposed, although intermediate doses or a reduced frequency of 
dosing may be selected by the SAC. 
Once the MTD is exceeded, the SAC may decide to further explore the P2D in a maximum of 6 
additional patients. The P2D may be any dose at or below the MTD. If the MTD is not reached, 
the P2D will not exceed the maximum dose tested in Phase I. The P2D dose will be established 
by the SAC and the sponsor, and may take into consideration the MTD, AurA and AurB target 
engagement, and PK at each dose level. 
3.2. 
Overall Study Design and Plan – Phase II 
Phase II will evaluate the preliminary efficacy of AK-01 in up to 4 cohorts; initially in patients 
with locally advanced or metastatic  SLCL and BC, and subsequently, at sponsor’s discretion, in 
patients with TNBC and/or HPV associated squamous cell cancers of the head neck and/or any 
other solid tumor of interest.tumor type that warrant further exploration. Up to 2030 patients 
may be enrolled in each cohort, giving an estimated total of 80120 patients.  Since AK-01 is an 
experimental treatment, patients will need to have failed standard of care therapies (i.e.,  
platinum-based therapy for SCLC; hormone therapy and a CDK4/6 inhibitor for BC; 
relapsed/resistant TNBC patients; standard therapy for HPV associated squamous cell cancers 
of the head neck) before being enrolled in this trial. 
Once the SAC has determined the MTD and P2D, enrollment may begin in Phase II. All open 
cohorts in Phase II may begin enrollment concurrently and will be dosed at the P2D 25 mg BID.  
Dose increases will not be allowed in Phase II. Dose modifications for toxicity are described in 
Section 3.3.2.  
After Cycle 1, dosing of AK-01 may continue in 21-day cycles until disease progression if the 
patient is receiving benefit, and is experiencing no severe toxicity in the opinion of the 
investigator. 
3.3.1. Potential AEs 
Based on safety data of the ongoing Phase I part of the study, the following are considered as 
potential AEs: bone marrow toxicity including neutropenia and thrombocytopenia; 
gastrointestinal toxicity including mucositis and diarrhea; and corneal deposition with blurry 
vision and double vision.  Appropriate follow up and rapid therapy for any of these events 
should be undertaken 
3.3.2. Dose Modification for Toxicity 

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Table 1. AK-01 Dose Modifications for Toxicity 
Toxicity 
Dose Modification 
QTcF Prolongation 
 
˂Grade 2 
Continue at current dose level. 
Grade 2 (QTcF average of 
triplicate readings >480 msec) 
Reduce dosing frequency by one dose level without 
interruption (see Table 2). If the event recurs, the dose 
may be withheldreduced a second time. If the event 
recurs a third time, dosing may only continue with 
sponsor approval. 
Grade 3 (QTcF average of 
triplicate readings >500 msec) 
 
Withhold AK-01 for up to 14 days. If QTcF returns to 
within 30 msec of baseline or <450 msec within 14 
days, treatment may be resumed at a reduced dosing 
frequency (see Table 2). If the event recurs a second 
time, the dose may again be reduced withheld and 
resumed after 14 days providingproviding the above 
criteria are met after 14 days. If a third occurrence is 
documented, treatment must be terminated. 
Grade 4 (QTcF average of 
triplicate readings >500 msec or 
>60 msec change from baseline, 
and TdP or polymorphic 
ventricular tachycardia or 
signs/symptoms of serious 
arrhythmia) 
Treatment should be terminated. 

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Other Non-Hematologic Toxicity 
 
Grade ≤2 
Continue at current dose level. 
Grade 3 (except alopecia, 
nausea, vomiting or diarrhea) not 
optimally managed per 
institutional guidelines 
Withhold AK-01 until event returns to Grade 1 or 
baseline. The first time the event occurs, maintain the 
AK-01 dose level when dosing is resumed.  
Each time the Grade 3 event recurs, withhold AK-01 
until event returns to Grade 1 or baseline, then 
decrease AK-01 by one dosing frequency level- when 
dosing is resumed (see Table 2). The dose level may be 
reduced successively each time the event recurs until 
the dose is 25 mg BID. If the event recurs at 25 mg 
BIDQD, the patient will be withdrawn. 
Grade 4 (except alopecia, 
nausea, vomiting or diarrhea) not 
optimally managed per 
institutional guidelines 
Patient will be withdrawn. Patient may not be 
rechallenged unless discussed with sponsor and 
approved by the SAC. 
Hematologic Toxicity 
 
Platelets ≤Grade 1 
ANC ≤Grade 1 on Day 1  
and/or 
ANC ≤Grade 2 on Day 8 or 15 
Continue at current dose level. 
Platelets ≥Grade 2, 
ANC ≥Grade 2 on Day 1, 
ANC ≥Grade 3 on Day 8 or 15, 
and/or  
≥Grade 3 platelets or ANC with 
spontaneous bleeding at any 
time 
Withhold AK-01 until platelets ≤Grade 1 and ANC 
≤Grade 1 (Day 1) or ≤Grade 2 (Day 8 or 15). Consider 
granulocyte colony stimulating factor (G-CSF) for low 
ANC. Decrease AK-01 by one dosing frequencylevel 
(see Table 2) when dosing is resumed.  
Each time the Grade 3 event recurs, withhold AK-01 
until counts recover. Consider G-CSF for low ANC. The 
dose level may be reduced successively each time the 
event recurs until the dose is 25 mg BID. If the event 
recurs at 25 mg QD BID, the patient will be withdrawn. 
 
The sponsor must be notified of dose reductions; once the dose has been reduced twice for a 
given patient, the SAC and sponsor must approve all subsequent dose reductions.  Given the 

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P2D of 25mg BID, the only dose reduction allowed will be a reduction in dosing frequency from 
25mg BID to 25mg QD.Sequential dose reductions are permitted to a minimum dose of 25 mg 
BID, after which a patient will be withdrawn. describes AK-01 dose reductions for toxicity 
throughout the study.  
3.4.  
Discussion of Design and Control 
Phase I is a dose escalation study with a modified 3 + 3 design. The 3+3 design is modified to 
allow expansion of a cohort with 3 additional patients if 1 DLT is observed in 6 patients for a 
total of 9 patients in the cohort (see Figure 2).  The rules-based 3 + 3 method for dose 
escalation is well-established, safe, and does not require real-time PK or computational 
modeling.8 Intrapatient dose escalation is permitted to allow each patient to potentially receive 
a maximum tolerated dose of AK-01 (see Section 3.1.4). In Phase II, preliminary efficacy of AK-
01 will be assessed in up to 34 cohorts (BC, SCLC, one TNBC, SCC-HN, and/or OT solid tumor of 
interest). Preclinical evidence indicates AK-01 may be particularly efficacious in these tumor 
types. 
Since this is not a comparison study, the use of a placebo control is not applicable. 
3.6. 
Determination of Sample Size 
In Phase II, up to 2030 patients for each tumor type will be administered IMP (up to 80120 
patients total). An observed ORR (proportion of partial or complete responders by RECIST) of 
≥20% with a durability of at least 4 months will be considered evidence of efficacy. With 15 
patients in a cohort, there is approximately 60% power to reject the null hypothesis of the ORR 
being ≤5% when the true ORR is 20% using a one-sided exact test for a single proportion at a 
significance level of 0.05. The power for this statistical test for a single tumor type without any 
adjustment for multiplicity is provided in Table 3 using various observed ORRs. 
4.  
STUDY POPULATION 
4.1. 
Criteria for Enrollment 
4.1.1. Inclusion Criteria 
Patients who meet all of the following inclusion criteria will be eligible for enrollment in the 
study: 
1. Are ≥18 years of age. 
2. Have given written informed consent prior to any study-specific procedures. 
3. Are willing to make themselves available for the duration of the study, and are willing to 
follow study procedures. 
4. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) 
scale (see Appendix 4). 
5. Have an estimated life expectancy of ≥12 weeks. 
6. Have adequate organ function including: 

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a. Hematologic: ANC ≥1.5 x 109/L, platelets ≥100 x 109/L, and hemoglobin ≥90 g/L. 
Patients may receive red blood cell transfusions to achieve this hemoglobin level at 
the discretion of the investigator. 
b. Hepatic: Albumin ≥30 g/L, bilirubin ≤1.5 times ULN, ALT and AST ≤2.5 times ULN.  If 
the liver has tumor involvement, AST and ALT ≤5 times ULN are acceptable. 
c. Renal: Estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2 (see Appendix 
3) 
7. Have discontinued all chemotherapy, investigational therapy, molecularly targeted 
therapy, and cancer-related hormonal therapy at least 14 days prior to study enrollment 
(6 weeks for mitomycin-C or nitrosoureas). 
8. Have discontinued biologic therapy and immunotherapy at least 21 days prior to study 
enrollment or have recovered from all AE to baseline or Grade 1 with the exception of 
alopecia or Grade 2 neuropathy.  
9. Patients who have had radiation therapy must be fully recovered in the opinion of the 
investigator prior to enrolling on study. 
10. Are recovered or recovering from the acute adverse effects of any chemotherapy, 
biologic therapy, immunotherapy, molecularly-targeted therapy, cancer-related hormonal 
therapy, and investigational therapy (≤Grade 1 or baseline), with the exception of 
alopecia or Grade 2 neuropathy. 
11. Have received at least 1 but no more than 4 prior systemic therapies for locally advanced 
or metastatic disease.  Hormone therapies are not considered in the determination of 
number of prior lines of systemic therapies. 
12. Patients who have had surgery must be fully recovered in the opinion of the investigator 
prior to enrolling on study. 
13. Female patients with reproductive potential must agree to use 2 forms of highly effective 
contraception during the study and for at least 3 months following the last dose of IMP. 
Sexually active male patients must use a barrier method of contraception (condom) 
during the study and for at least 3 months following the last dose of IMP. 
14. Females with child-bearing potential must have had a negative pregnancy test result 
≤28 days prior to the first dose of IMP, as well as ≤1 day prior to the first dose of IMP. 
15. Patients must be, in the judgment of the investigator, appropriate candidates for 
experimental therapy, and no standard therapy would confer clinical benefit to the 
patients. 
Phase I 
16. Patients must have histological or cytological evidence of cancer (solid tumors, excluding 
primary brain tumor) that is evaluable, and locally advanced and/or metastatic. 
Phase II 
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18. Patients must have histological or cytological evidence of a solid tumor that is locally 
advanced and/or metastatic and have failed locally approved therapies that have clinical 
benefit as follows: 
a. SCLC 
• Must have failed platinum-containing therapy, but be in a platinum sensitive 
relapse (having responded to up to 6 cycles of platinum therapy with at least 
SD, PR, or CR, and then maintained that response without progression for 3 
months after the last platinum dose.  Patients could have received maintenance 
therapy following the completion of platinum therapy.  Patient who never 
responded or progressed <3 months after the last platinum dose are not 
eligible); 
b. BC 
• ER+ and/or PR+ but HER2-negative (see Appendix 8 for eligible biomarker 
expression). 
• May have failed up to 2 prior chemotherapy regiments. 
• Must have failed a hormone therapy and a CDK4/6 inhibitor. 
c. A solid tumor type that has been approved by the sponsor. 
d. TNBC 
• Must have recurrent/refractory TNBC, defined as any breast cancer that 
expresses <1% ER, <1% PR, and is HER-2 negative (immunohistochemistry 
staining of 0 or +1, or no evidence of amplification using single or -dualprobe- in 
situ hybridization). Must have failed standard therapy. 
e. SCC-HN 
• For HPV associated squamous cell cancers of the head neck, must have failed 
standard therapy. 
f. OT 
• To be determined by the sponsor. 
 
5.1. 
Rationale for Selection of Dose 
The 25 mg BID has been chosen by the SAC and sponsor as the dose of Phase II.  Dose selection 
was based on the MTD, AurA and AurB target engagement, and PK from Phase I (Section 1.3). 
The predicted efficacious dose is planned to be administered to the third cohort (i.e. after 2 
dose escalation steps, each ≤3 fold the previous dose).  Once the 200 mg BID dose is reached, 
dose escalation steps will continue based on safety in ≤2 fold steps up to the highest proposed 
dose of 800 mg BID.  The 800 mg BID dose (1600 mg daily) is approximately double the 90% 
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Table 4 
Proposed AK-01 Dosing  
Dose Level 
Capsules Administered 
Total Daily Dose 
25 mg QD 
1 × 25 mg (morning) 
25 mg 
25 mg BID 
1 × 25 mg (morning) 
1 × 25 mg (evening) 
50 mg 
75 mg BID 
3 × 25 mg (morning) 
3 × 25 mg (evening) 
150 mg 
200 mg BID 
2 × 100 mg (morning) 
2 × 100 mg (evening) 
400 mg 
400 mg BID 
4 × 100 mg (morning) 
4 × 100 mg (evening) 
800 mg 
600 mg BID 
6 × 100 mg (morning) 
6 × 100 mg (evening) 
1200 mg 
800 mg BID 
8 × 100 mg (morning) 
8 × 100 mg (evening) 
1600 mg 
 
5.3. 
Method of Assignment to Treatment 
In Phase II a patient’s tumor type will determine their allocation to cohort. Study centers will 
enroll competitively as eligible patients become available.  The patients will be allocated to IMP 
only after the registration form is signed by both the investigator and sponsor representative. 
 
6.2. 
Pharmacodynamic Evaluations 
6.2.1. Samples for Pharmacodynamic Evaluations 
In Phase I, pre-treatment and on-treatment skin biopsies will be mandatory for all patients pre-
treatment and on-treatment (see Appendix 1). For all Phase I patients enrolled in the P2D 
confirmation cohorts (after identification of the MTD, see Section 3.1.3), pre-treatment and on-
treatment biopsies of primary or metastatic tumor will also be required (see Appendix 1). For 
all patients enrolled in Phase II, tumor biopsies will be required from either a primary or 
metastatic tumor site.  SCLC patients tumor biopsies will be required unless the primary or 
metastatic tumor site is inaccessible or a quality biopsy cannot be obtained. The initial tumor 
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the second biopsy should be collected at C2D8, ± 3 days.  Archived specimen(s) from a 
diagnostic biopsy and/or surgery of the tumor collected within 3 months of screening may be 
requested instead of pre-treatment tumor biopsy as long as the biopsy was obtained after they 
had already failed previously therapy. Tumor samples may be used for both PD and molecular 
profile analyses (see Section 6.3). 
The results of PD analyses in Phase I will determine which PD samples (skin and/or tumor 
biopsies) will be collected for Phase II.  The sponsor will inform investigators which samples will 
be required prior to opening enrollment of Phase II; all samples requested will be mandatory. In 
addition to samples for PD analysis, a pre-treatment tumor biopsy will be required for all 
patients in Phase II for analysis of molecular profile (see Section 6.3.1); 
6.2.2 Evaluation of Target Engagement 
Markers of dose-dependent target engagement will be evaluated, which may include 
assessment of levels of phospho-histone H3 and markers of apoptosis, phosphorylation, DNA 
damage, and mitosis.  Samples may be assessed using immunohistochemistry, Western 
blotting, ELISA, or other techniques, and will be compared across time points. The inhibition of 
AurA and AurB by AK-01 will be compared. Markers of dose-dependent target engagement may 
be compared between skin (collected in phase I) and tumor tissue. 
6.3. 
Molecular Profile Evaluation 
6.3.1. Samples for Molecular Profile Evaluations 
A pre-treatment tumor biopsy is required for all patients in Phase II for assessment of molecular 
profile (SCLC tumor/metastatic site biopsies are collected if possible). If available, archived 
sample(s) from a diagnostic biopsy/surgery of the primary or metastatic tumor collected prior 
to within 3 months of enrollment may be requested instead as long as the biopsy was obtained 
after they had already failed previously therapy. Any other tumor samples collected in the 
course of the study may also be profiled (see Section 6.2.1).  
6.3.2. Evaluation of Molecular Profile 
DNA and/or proteins from tumor samples and blood may be analyzed using immunohisto 
chemistry staining, next generation sequencing or other technology to identify the presence of 
certain proteins or DNA mutations (e.g., Rb, PTEN, myc, and TP53). Somatic mutations may be 
identified through analysis of paired data from tumor tissue and blood, if data is not already 
available in patient histories. These samples may be used to evaluate the genetic mechanisms 
underlying response to AK-01. 
6.4.  
Storage of Samples 
Biological samples collected for analysis of PD or molecular profile (i.e., blood, serum, plasma, 
skin (phase I only), and tumor tissue) will be retained for a maximum of 15 years following the 
last patient visit. 
Appendix 1. 
Schedule of Events 
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Footnotes related to skin and tumor biopsy updated per revised Section 6.3. 
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation10 
At all study sites, the CKD-EPI equation maymust be used to calculate eGFR as follows: 
  GFR = 141 × min (Scr/κ, 1)α × max(Scr/κ, 1)-1.209 × 0.993age × 1.018 [if female] × 1.159 [if black]  
 
where: 
Scr is serum creatinine in µmol/L 
κ is 61.9 for females and 79.6 for males 
α is -0.329 for females and -0.411 for males 
min indicates the minimum of Scr /κ or 1 
and max indicates the maximum of Scr /κ or 1