A Multicenter, Open-Label, Parallel, Phase 1b/2a Study of PLX2853 in Combination With Abiraterone Acetate and Prednisone and Phase 1b/2a Study of PLX2853 in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Phase: PHASE1
Conditions: Metastatic Castration-resistant Prostate Cancer
Sponsor: Opna Bio LLC

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PLX2853 
Protocol PLX124-04 Amendment 3, 29 Oct 2021 
CONFIDENTIAL/PROPRIETARY 
Page 3 of 148 
Plexxikon Inc. 
INVESTIGATOR AGREEMENT AND SIGNATURE 
Protocol PLX124-04: 
A Multicenter, Open-Label, Parallel, Phase 1b/2a Study of 
PLX2853 in Combination with Abiraterone Acetate and Prednisone 
and Phase 1b/2a Study of PLX2853 in Combination with Olaparib 
in Subjects with Metastatic Castration-Resistant Prostate Cancer 
(mCRPC) 
Sponsor: 
Plexxikon Inc. 
329 Oyster Point Blvd. 
South San Francisco, CA 94080, USA 
Telephone:  (510) 647-4000 
I have read and approved this protocol. My signature, in conjunction with the signature of the 
Sponsor, confirms the agreement of both parties that the clinical study will be conducted in 
accordance with the protocol and all applicable laws and regulations including, but not limited 
to, the International Conference on Harmonisation Guideline for Good Clinical Practice (GCP), 
the Code of Federal Regulations (CFR), and the ethical principles that have their origins in the 
Declaration of Helsinki. I agree to inform all who assist me in the conduct of this study of their 
responsibilities and obligations. 
Nothing in this document is intended to limit the authority of a physician to provide emergency 
medical care under applicable regulations. 
Principal Investigator Signature 
Date 
Principal Investigator Name and Title (print) 
Investigational site or name of institution and location (printed) 

PLX2853 
Protocol PLX124-04 Amendment 3, 29 Oct 2021 
CONFIDENTIAL/PROPRIETARY 
Page 4 of 148 
Plexxikon Inc. 
TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL ...............................................................................................1 
SPONSOR SIGNATURE ..............................................................................................................2 
INVESTIGATOR AGREEMENT AND SIGNATURE .............................................................3 
TABLE OF CONTENTS ..............................................................................................................4 
LIST OF TABLES ...............................................................................................................9 
LIST OF FIGURES .............................................................................................................9 
LIST OF ABBREVIATIONS AND GLOSSARY OF TERMS ...............................................10 
PROTOCOL SYNOPSIS ............................................................................................................13 
SYNOPSIS TABLE 1:  PHASE 1B PLX2853 + ABIRATERONE/PREDNISONE 
OR PLX2853 + OLAPARIB DOSE ESCALATION SCHEDULE OF 
EVENTS ................................................................................................................29 
SYNOPSIS TABLE 2:  PHASE 2A PLX2853 + ABIRATERONE 
ACETATE/PREDNISONE OR PLX2853 + OLAPARIB DOSE 
EXPANSION SCHEDULE OF EVENTS.............................................................33 
1.0 
BACKGROUND AND STUDY RATIONALE .............................................................37 
1.1 
Background ............................................................................................................37 
1.2 
Evidence of a Role for BET Proteins in Solid Tumors ..........................................37 
1.3 
Role of BET Inhibitors in Metastatic Castration Resistant Prostate Cancer .........38 
1.3.1 
Metastatic Castration Resistant Prostate Cancer ...................................38 
1.3.2 
Combination of BET Inhibitors with AR Signaling Inhibitors .............38 
1.3.3 
Combination of BET Inhibitors with PARP Inhibitors .........................39 
1.4 
PLX2853 ................................................................................................................39 
1.4.1 
Nonclinical Pharmacology ....................................................................39 
1.4.2 
Nonclinical Pharmacokinetics ...............................................................43 
1.4.3 
Toxicology Studies of PLX2853 ...........................................................45 
1.4.4 
Proposed Starting Dose for Study PLX124-04 .....................................49 
1.5 
Study Rationale ......................................................................................................49 
1.6 
Potential Risks and Benefits ..................................................................................51 
1.7 
Previous Pharmacokinetics and Pharmacodynamics Experience ..........................52 
1.7.1 
PLX2853 Clinical Pharmacokinetics ....................................................52 
1.7.2 
PLX2853 Clinical Pharmacodynamics .................................................53 
2.0 
STUDY OBJECTIVES ....................................................................................................55 
2.1 
PLX2853 + Abiraterone Acetate + Prednisone Combination ...............................55 
2.1.1 
Phase 1b (Dose Escalation) ...................................................................55 
2.1.2 
Phase 2a (Dose Expansion) ...................................................................55 
2.2 
PLX2853 + Olaparib Combination ........................................................................55 

PLX2853 
Protocol PLX124-04 Amendment 3, 29 Oct 2021 
CONFIDENTIAL/PROPRIETARY 
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Plexxikon Inc. 
2.2.1 
Phase 1b (Dose Escalation) ...................................................................55 
2.2.2 
Phase 2a (Dose Expansion) ...................................................................56 
2.3 
Exploratory Objectives (Both Phases, Both Combinations) ..................................56 
3.0 
STUDY DESIGN ..............................................................................................................57 
3.1 
PLX2853 + Abiraterone Acetate + Prednisone Combination Therapy .................57 
3.1.1 
Phase 1b – Determination of RP2D of PLX2853 in Combination 
with Abiraterone Acetate and Prednisone .............................................57 
3.1.2 
Phase 2a – Dose Expansion for Combination of PLX2853 + 
Abiraterone + Prednisone ......................................................................58 
3.1.3 
Pharmacokinetics of PLX2853 and Abiraterone ...................................58 
3.2 
PLX2853 + Olaparib Combination Therapy .........................................................58 
3.2.1 
Phase 1b – PLX2853 + Olaparib ...........................................................59 
3.2.2 
Phase 2a – Dose Expansion for Combination of PLX2853 + 
Olaparib .................................................................................................59 
3.2.3 
Pharmacokinetics of PLX2853 and Olaparib ........................................60 
3.3 
Number of Subjects................................................................................................60 
3.4 
Duration of Study ...................................................................................................61 
3.5 
Endpoints ...............................................................................................................61 
3.5.1 
PLX2853 + Abiraterone Acetate + Prednisone Combination ...............61 
3.5.1.1 
Phase 1b – Primary Endpoint ...................................................61 
3.5.1.2 
Phase 2a – Primary Endpoints .................................................61 
3.5.2 
PLX2853 + Olaparib Combination .......................................................62 
3.5.2.1 
Phase 1b – Primary Endpoint ...................................................62 
3.5.2.2 
Phase 2a – Primary Endpoint ...................................................62 
3.5.3 
Both Phases, Both Combinations ..........................................................62 
3.5.3.1 
Both Phases – Secondary Endpoints ........................................62 
3.5.3.2 
Both Phases – Exploratory Endpoints......................................63 
3.6 
Randomization .......................................................................................................63 
4.0 
STUDY POPULATION ..................................................................................................64 
4.1 
Inclusion Criteria ...................................................................................................64 
4.2 
Exclusion Criteria ..................................................................................................66 
4.2.1 
Birth Control Methods ..........................................................................69 
5.0 
STUDY TREATMENTS .................................................................................................70 
5.1 
Investigational Product and Test Article Properties ..............................................70 
5.1.1 
PLX2853 (Investigational Product) ......................................................70 
5.1.2 
Abiraterone Acetate (Test Article) ........................................................70 
5.1.3 
Prednisone (Test Article) ......................................................................70 

PLX2853 
Protocol PLX124-04 Amendment 3, 29 Oct 2021 
CONFIDENTIAL/PROPRIETARY 
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Plexxikon Inc. 
5.1.4 
Olaparib (Test Article) ..........................................................................70 
5.2 
Study Drug Administration ....................................................................................70 
5.2.1 
PLX2853 Administration ......................................................................70 
5.2.2 
Abiraterone Acetate Administration .....................................................71 
5.2.3 
Prednisone Administration ....................................................................71 
5.2.4 
Olaparib Administration .......................................................................71 
5.2.5 
Dosing on PK Sample Collection Days ................................................71 
5.3 
PLX2853 Dose Escalation .....................................................................................72 
5.4 
Dose Escalation Plan..............................................................................................72 
5.4.1 
Dose Escalation Plan for the Combination of PLX2855 + 
Abiraterone Acetate + Prednisone ........................................................72 
5.4.2 
Dose Escalation Plan for Combination of PLX2853 + Olaparib ..........74 
5.5 
Concomitant Medications (and Procedures) ..........................................................75 
5.6 
Precautions and Restrictions ..................................................................................77 
5.7 
Management of Clinical Events .............................................................................77 
5.8 
Blinding and Unblinding........................................................................................77 
5.9 
Preparation, Reconstitution, and Dispensation ......................................................78 
5.10 
Packaging and Labeling .........................................................................................78 
5.11 
Storage, Handling, and Accountability ..................................................................78 
5.12 
Other Protocol-specified Materials ........................................................................79 
6.0 
DOSE-LIMITING TOXICITIES AND DOSE MODIFICATIONS ...........................80 
6.1 
Definitions of Dose-limiting Toxicity ...................................................................80 
6.2 
Dose Modification Guidelines ...............................................................................81 
7.0 
STUDY CONDUCT AND ASSESSMENTS .................................................................87 
7.1 
Study Conduct ........................................................................................................87 
7.1.1 
Study Personnel and Organizations ......................................................87 
7.1.2 
Study Committee ...................................................................................87 
7.1.3 
Arrangements for Recruitment of Subjects ...........................................87 
7.1.4 
Treatment Group Assignments .............................................................88 
7.1.5 
Withdrawal of Subjects from Drug Treatment and Study, and 
Subject Replacement .............................................................................88 
7.1.6 
Study Compliance .................................................................................88 
7.1.7 
Enrollment of Subjects ..........................................................................89 
7.1.8 
Protocol Deviations ...............................................................................89 
7.2 
Study Assessments .................................................................................................89 
7.2.1 
Disease Assessment ..............................................................................90 
7.2.1.1 
Soft Tissue Evaluation .............................................................91 

PLX2853 
Protocol PLX124-04 Amendment 3, 29 Oct 2021 
CONFIDENTIAL/PROPRIETARY 
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7.2.1.2 
Bone Metastasis Evaluation .....................................................91 
7.2.1.3 
PSA Evaluation ........................................................................91 
7.2.1.4 
Symptomatic Skeletal-Related Events (SSRE) ........................92 
7.2.2 
Archival Tissue .....................................................................................92 
7.2.3 
Fresh Tumor Biopsy ..............................................................................92 
7.2.4 
Pharmacokinetic and Pharmacodynamic Assessments .........................92 
7.2.5 
Pharmacokinetic Assessments ..............................................................93 
7.2.6 
Biomarker Samples and Pharmacogenomics ........................................93 
7.2.7 
Safety Assessments ...............................................................................95 
7.2.7.1 
Medical and Medication History .............................................95 
7.2.7.2 
ECOG Performance Status Assessment ...................................95 
7.2.7.3 
Physical Examinations .............................................................95 
7.2.7.4 
Vital Signs ................................................................................95 
7.2.7.5 
Height and Weight ...................................................................95 
7.2.7.6 
Electrocardiogram ....................................................................96 
7.2.7.7 
Safety Laboratory Assessments ...............................................96 
7.3 
Blood Collection ....................................................................................................96 
8.0 
STATISTICAL AND QUANTITATIVE ANALYSES ................................................99 
8.1 
Randomization and Stratification ..........................................................................99 
8.2 
Definitions and Populations for Analysis ..............................................................99 
8.2.1 
Evaluable Populations ...........................................................................99 
8.3 
Procedures for Handling Missing, Unused, and Spurious Data.............................99 
8.4 
General Methodology ............................................................................................99 
8.5 
Baseline Comparisons ............................................................................................99 
8.6 
Efficacy Analysis ...................................................................................................99 
8.7 
Safety Analysis ....................................................................................................101 
8.8 
Pharmacokinetics, Pharmacodynamics, Biomarkers ...........................................101 
8.8.1 
Pharmacokinetic Analysis ...................................................................101 
8.8.2 
Pharmacodynamic and Other Biomarker Analysis .............................102 
8.9 
Analysis and Sample Size ....................................................................................102 
8.9.1 
Phase 1b – PLX2853 + Abiraterone Acetate + Prednisone 
Combination and PLX2853 + Olaparib Combination Analysis and 
Sample Size .........................................................................................102 
8.9.2 
Phase 2a (Dose Expansion) – PLX2853 + Abiraterone Acetate + 
Prednisone Combination Analysis and Sample Size ..........................102 
8.9.3 
Phase 2a (Dose Expansion) – PLX2853 + Olaparib Combination 
Analysis and Sample Size ...................................................................103 

PLX2853 
Protocol PLX124-04 Amendment 3, 29 Oct 2021 
CONFIDENTIAL/PROPRIETARY 
Page 8 of 148 
Plexxikon Inc. 
8.10 
Interim Analysis ...................................................................................................103 
9.0 
ASSESSMENT OF SAFETY AND ADVERSE EVENTS .........................................104 
9.1 
Definitions............................................................................................................104 
9.1.1 
Adverse Event Definition ....................................................................104 
9.1.2 
Serious Adverse Event Definition .......................................................105 
9.2 
Procedures for Recording and Reporting Adverse Events, Serious 
Adverse Events, and Adverse Events of Special Interest ....................................105 
9.3 
Timing of Evaluation of Adverse Events and Serious Adverse Events...............107 
9.3.1 
Adverse Events of Special Interest .....................................................108 
9.3.2 
Worsening of Cancer ..........................................................................108 
9.3.3 
Overdose .............................................................................................108 
9.4 
Monitoring of Adverse Events and Period of Observation ..................................108 
9.5 
Procedures for Reporting Drug Exposure During Pregnancy and Birth Events ..109 
10.0 
ADMINISTRATIVE REQUIREMENTS ....................................................................110 
10.1 
Good Clinical Practice .........................................................................................110 
10.2 
Data Quality Assurance .......................................................................................110 
10.3 
Electronic Case Report Form Completion ...........................................................110 
10.4 
Study Monitoring .................................................................................................110 
10.5 
Ethical Considerations .........................................................................................111 
10.6 
Subject Information and Informed Consent .........................................................111 
10.7 
Subject Confidentiality ........................................................................................111 
10.8 
Investigator Compliance ......................................................................................111 
10.9 
On-site Audits ......................................................................................................112 
10.10 Investigator and Site Responsibility for Drug Accountability .............................112 
10.11 Product Complaints ..............................................................................................112 
10.12 Closure of the Study.............................................................................................112 
10.13 Record Retention .................................................................................................113 
10.14 Publication and Use of Information .....................................................................113 
11.0 
REFERENCES ...............................................................................................................115 
APPENDIX 1: 
LABORATORY TESTS .............................................................................121 
APPENDIX 2: 
STRONG CYP3A4 AND/OR CYP2C8 INHIBITORS AND 
INDUCERS AND CYP2D6 SUBSTRATES WITH A NARROW 
THERAPEUTIC INDEX ..............................................................................................124 
APPENDIX 3: 
RECIST CRITERIA VERSION 1.1 ..........................................................125 
APPENDIX 4: 
DRUGS CLEARLY ASSOCIATED WITH THE RISK OF 
TORSADES DE POINTES (TDP) AND QT PROLONGATION ............................137 
APPENDIX 5: 
ECOG PERFORMANCE STATUS ...........................................................138 

PLX2853 
Protocol PLX124-04 Amendment 3, 29 Oct 2021 
CONFIDENTIAL/PROPRIETARY 
Page 9 of 148 
Plexxikon Inc. 
APPENDIX 6: 
PCWG3 CASTRATION-RESISTANT PROSTATE CANCER 
CLINICAL TRIAL RECOMMENDATIONS AND CRITERIA .............................139 
 
LIST OF TABLES 
Table 1: 
Kd Values of PLX2853 for Binding to the 8 Bromodomains from 4 BET 
Proteins ..................................................................................................................40 
Table 2: 
IC50 Values for PLX2853, Enzalutamide, and Niraparib in Prostate Cancer 
Cell Growth Assays ...............................................................................................41 
Table 3: 
Overview of PLX2853 Toxicology Program .........................................................46 
Table 4: 
Provisional PLX2853 Dose Escalation Plan for the Combination of PLX2853 
+ Abiraterone Acetate + Prednisone ......................................................................73 
Table 5: 
Provisional Dose Escalation Plan for the Combination of PLX2853 + Olaparib ..74 
Table 6: 
Recommended PLX2853 Dose Modifications ......................................................83 
Table 7: 
Contact Information ...............................................................................................87 
Table 8: 
Radiographic Progression Criteria .........................................................................91 
Table 9: 
Phase 1b:  Approximate Blood Sample Volumes Collected .................................97 
Table 10: 
Phase 2a:  Approximate Blood Sample Volumes Collected ..................................98 
Table 11: 
Time Point Response:  Subjects with Targets (± Non-target) Disease ................134 
Table 12: 
Time Point Response:  Subjects with Non-target Disease Only ..........................134 
Table 13: 
Best Overall Response When Confirmation of CR and PR Required .................135 
 
LIST OF FIGURES 
Figure 1: 
PLX2853 in Combination with Abiraterone and Enzalutamide in the 22Rv1 
Xenograft Model ....................................................................................................42 
Figure 2: 
PLX2853 Pharmacodynamic Effect on Peripheral Blood Cells in 
Study PLX124-01 (Subjects with Solid Tumors) ..................................................53 
Figure 3: 
PLX2853 Pharmacodynamic Effect in Peripheral Blood and Bone Marrow 
Cells in PLX124-02 (AML/MDS) .........................................................................54 
Figure 4: 
Study Schema, PLX2853 + Abiraterone Acetate + Prednisone Combination 
Therapy ..................................................................................................................57 
Figure 5: 
Study Schema, PLX2853 + Olaparib Combination Therapy.................................59 
 

PLX2853 
Protocol PLX124-04 Amendment 3, 29 Oct 2021 
CONFIDENTIAL/PROPRIETARY 
Page 10 of 148 
Plexxikon Inc. 
LIST OF ABBREVIATIONS AND GLOSSARY OF TERMS 
Abbreviation or Term 
Definition/Explanation 
ADT 
androgen deprivation therapy 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
aPTT 
activated partial thromboplastin time 
AR 
androgen receptor 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
AUC0- 
area under the concentration-time curve from time zero extrapolated to infinite time 
AUC0-24 
area under the concentration-time curve from time zero to 24 hours postdose 
AUC0-last 
area under the concentration-time curve from time zero to time of last measurable 
concentration postdose 
BCRP 
breast cancer resistance protein 
BET 
bromodomain and extra terminal domain 
BRD 
bromodomain-containing protein 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CI90 
90% confidence interval 
CI95 
95% confidence interval 
CL 
clearance 
Cmax 
maximum observed concentration 
CLIA 
Clinical Laboratory Improvement Amendments 
CR 
complete response 
CrCl 
creatinine clearance 
CRF 
case report form 
CRO 
contract research organization 
CRP 
c-reactive protein 
CT 
computed tomography 
CTC 
circulating tumor cell  
CxDx 
Cycle x Day x 
CYP 
cytochrome P450 
DCR 
disease control rate 
DLT 
dose-limiting toxicity 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EOC 
epithelial ovarian cancer 
ESI+ 
electrospray ionization in positive ion mode 
FDG PET 
(18)F-fluorodeoxyglucose positron-emission tomography 

PLX2853 
Protocol PLX124-04 Amendment 3, 29 Oct 2021 
CONFIDENTIAL/PROPRIETARY 
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Abbreviation or Term 
Definition/Explanation 
FU 
follow-up 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HNSTD 
highest non-severely toxic dose 
HPLC 
high performance liquid chromatography 
IBW 
ideal body weight 
IC 
inhibitory concentration 
ICH 
International Council for Harmonisation 
IND 
Investigational New Drug 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
IV 
intravenous, intravenously 
Kd 
dissociation constant 
LC/MS/MS 
liquid chromatography tandem mass spectrometry 
mCRPC 
metastatic castration-resistant prostate cancer 
MDCK 
Madin-Darby canine kidney 
MedDRA 
Medical Dictionary for Drug Regulatory Activities 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NGS 
next generation sequencing 
NOAEL 
no-observed-adverse-effect level 
OAT 
organic anion transporter 
OATP 
organic anion transporting polypeptide 
OCCC 
ovarian clear cell carcinoma 
ORR 
overall response rate 
OS 
overall survival 
PARP 
poly-(ADP-ribose) polymerase 
PCWG3 
Prostate Cancer Working Group 3  
PD 
progressive disease or pharmacodynamic 
PFS 
progression-free survival 
PG 
pharmacogenomics 
P-gp 
P-glycoprotein 
PK 
pharmacokinetic(s) 
PR 
partial response 
PSA 
prostate-specific antigen 
PT 
prothrombin time 
QD 
once daily 
QTc 
QT interval corrected 
QTcF 
QT interval corrected using Fridericia’s formula 

PLX2853 
Protocol PLX124-04 Amendment 3, 29 Oct 2021 
CONFIDENTIAL/PROPRIETARY 
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Plexxikon Inc. 
Abbreviation or Term 
Definition/Explanation 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SD 
stable disease 
SSRE 
Symptomatic Skeletal-Related Events 
T1/2 
terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
TGI 
tumor growth inhibition 
Tmax 
time to maximum observed concentration 
ULN 
upper limit of normal 
UV 
ultraviolet 
 

PLX2853 
Protocol PLX124-04 Amendment 3, 29 Oct 2021 
CONFIDENTIAL/PROPRIETARY 
Page 13 of 148 
Plexxikon Inc. 
PROTOCOL SYNOPSIS 
Title: 
A Multicenter, Open-Label, Parallel, Phase 1b/2a Study of PLX2853 in Combination with 
Abiraterone Acetate and Prednisone and Phase 1b/2a Study of PLX2853 in Combination 
with Olaparib in Subjects with Metastatic Castration-Resistant Prostate Cancer (mCRPC) 
Sponsor: 
Plexxikon Inc. 
Clinical Phase: 
Phase 1b/2a  
Indication: 
For PLX2853, abiraterone acetate, and prednisone combination:  mCRPC with 
progression while currently receiving initial treatment with abiraterone acetate and 
prednisone 
For PLX2853 and olaparib combination:  deleterious or suspected deleterious germline or 
somatic homologous recombination repair (HRR) gene-mutated mCRPC with progression 
after treatment with abiraterone acetate/prednisone or with enzalutamide 
Objectives: 
PLX2853 + Abiraterone Acetate + Prednisone Combination 
Phase 1b: 
Primary Objectives 
• 
To evaluate the safety and tolerability of PLX2853 + abiraterone acetate + 
prednisone including dose limiting toxicities (DLTs), maximum tolerated dose 
(MTD), and recommended Phase 2 dose (RP2D) in subjects with mCRPC who 
develop disease progression while currently receiving initial treatment with 
abiraterone acetate and prednisone 
Secondary Objectives 
• 
To characterize the PK of PLX2853 and abiraterone and efficacy of PLX2853 
combined with abiraterone acetate + prednisone in subjects with mCRPC who 
develop disease progression while currently receiving initial treatment with 
abiraterone acetate and prednisone 
Phase 2a: 
Primary Objectives 
• 
To evaluate the efficacy of PLX2853 + abiraterone acetate + prednisone at the RP2D 
in subjects with mCRPC who develop disease progression while currently receiving 
initial treatment with abiraterone acetate and prednisone 
Secondary Objectives 
• 
To further characterize the safety and PK of PLX2853 and abiraterone when 
PLX2853 is combined with abiraterone acetate + prednisone in subjects with 
mCRPC who develop disease progression while currently receiving initial treatment 
with abiraterone acetate and prednisone 
 
PLX2853 + Olaparib Combination 
Phase 1b: 
Primary Objectives 
• 
To evaluate the safety and tolerability of PLX2853 + olaparib including dose limiting 
toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase 2 dose 
(RP2D) in subjects with deleterious or suspected deleterious germline or somatic 
homologous recombination repair (HRR) gene-mutated mCRPC who have 
progressed following prior treatment with abiraterone acetate and prednisone or with 
enzalutamide 
Secondary Objectives 
• 
To characterize the PK of PLX2853 and olaparib and efficacy of PLX2853 combined 
with olaparib in subjects with deleterious or suspected deleterious germline or 

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somatic homologous recombination repair (HRR) gene-mutated mCRPC who have 
progressed following prior treatment with abiraterone acetate and prednisone or with 
enzalutamide 
Phase 2a: 
Primary Objective 
• 
To evaluate the efficacy of PLX2853 + olaparib at the RP2D in subjects with 
deleterious or suspected deleterious germline or somatic homologous recombination 
repair (HRR) gene-mutated mCRPC who have progressed following prior treatment 
with abiraterone acetate and prednisone or with enzalutamide 
Secondary Objectives 
• 
To further characterize the safety and PK of PLX2853 and olaparib when PLX2853 
is combined with olaparib in subjects with deleterious or suspected deleterious 
germline or somatic homologous recombination repair (HRR) gene-mutated mCRPC 
who have progressed following prior treatment with abiraterone acetate and 
prednisone or with enzalutamide 
 
Exploratory Objectives – Both Phases, Both Combinations 
• 
To assess biomarkers in peripheral blood cells, tumor cells, and tissue biopsies 
• 
To further evaluate the pharmacodynamics (PD) of PLX2853 
Study Design: 
PLX2853 + Abiraterone Acetate + Prednisone Combination – Ph1b/2a Study Design 
This multicenter, open-label, 2-part study will evaluate the safety, PK, PD, and efficacy 
of PLX2853 + abiraterone acetate + prednisone combination therapy in subjects with 
mCRPC who develop disease progression, while currently receiving initial abiraterone 
acetate and prednisone therapy, as documented by radiographic imaging, prostate-specific 
antigen (PSA), or clinical assessment. The study schema is presented below. 
 
 
Phase 1b:  Dose Escalation 
In Phase 1b (dose escalation), the safety profile, RP2D/MTD, PK, and PD of PLX2853 
(administered orally once daily) in combination with abiraterone acetate (administered 
orally once daily) and prednisone (administered orally twice daily) in 21-day treatment 
cycles will be evaluated. Each cohort will be enrolled and assessed using a standard 
“3+3” design. The rules for determining DLT and dose escalation are defined further 
below. 

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The provisional dose escalation plan is detailed as follows: 
Provisional PLX2853 Dose Escalation Plan 
Dose 
Level 
PLX2853 Dose 
(mg/day)a 
Abiraterone Acetate Dose 
(mg/day)a 
Prednisone Dose  
(total mg/day)b 
-1 
20 
1000  
10 
1 
40 
1000  
10 
2 
80 
1000  
10 
a 
Once daily (QD) dosing schedule unless otherwise specified. Initial cohort will assess 
QD dosing. Subsequent cohorts may evaluate alternative dosing regimens as agreed 
to by the Study Committee. 
b 
5 mg twice daily (BID) dosing schedule. 
 
DLTs will be assessed in the first 21-day treatment cycle. In the absence of a DLT and in 
conjunction with review of the safety, PK, and available PD data from each dose cohort 
by the Study Committee, dose escalations are planned to occur in the following manner: 
• 
A minimum of 3 to 4 subjects will be initially enrolled in Dose Level 1 (Cohort 1). If 
a DLT is observed in 1 subject in a given cohort, up to 6 subjects will be treated at 
that dose. 
• 
If DLTs are observed in 2 or more subjects (or ≥33% of the cohort) at a dose level, 
the dose at which this occurs will be considered intolerable and the MTD to have 
been exceeded. The highest dose level at which 0 or 1 of 6 subjects experience a 
DLT will be declared the RP2D. 
• 
If Dose Level 1 is not tolerated, Dose Level -1 (20 mg/day) will be studied. If that 
dose level is intolerable, the study will be halted. 
• 
At least 6 subjects must be evaluable at a given dose level in order to be considered 
an RP2D. 
• 
An RP2D may be declared at a dose level without reaching an MTD if further dose 
escalation is deemed unwarranted. 
• 
Any subject who misses more than 25% of doses in Cycle 1 (e.g., ≥6 doses of 
PLX2853 in 21 days) for reasons other than a treatment-related adverse event (AE), 
or is withdrawn from the study prior to completing Cycle 1 for reasons other than a 
DLT, will not be DLT evaluable and additional subject(s) may be enrolled to provide 
adequate data for dose escalation decision making. 
After dosing has been completed in each cohort, safety, PK data, and PD data (if 
available) will be reviewed, and dose escalation decisions will be made by the Study 
Committee. Dose escalation decisions will also take into consideration safety information 
beyond the DLT period from earlier cohorts. If no DLT is observed, the recommended 
dose for further evaluation may be established based on toxicity, PK, convenience of 
dosing, and PD (if available) in subjects treated at that dose. Dose escalation will only be 
permitted if adequate safety and tolerability have been demonstrated at the previous lower 
dose for 21 days. Once all ongoing subjects in a dose cohort have been treated for at least 
two 21-day cycles and the safety and tolerability of that dose level has been established, 
intra-subject dose escalation to that dose level may be permitted for subjects enrolled at 
lower dose levels who have not experienced a Grade 3 or higher treatment-related toxicity 
and have completed 2 cycles of PLX2853. Any intra-subject dose escalation requires a 
discussion and agreement with the Medical Monitor. 
Phase 2a:  Dose Expansion 
In Phase 2a, efficacy as well as additional safety, PK, and PD information of PLX2853 in 
combination with abiraterone acetate and prednisone at the RP2D dose established in 
Phase 1b by the Study Committee will be obtained using a Simon’s 2-stage design. 

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Initially, 9 subjects will be enrolled to assess for efficacy in Phase 2a. If 2 or more 
responses are observed in the first 9 evaluable subjects, an additional 10 evaluable 
subjects will be enrolled. Subjects in Phase 2a who do not complete their 12-week disease 
response assessment for reasons other than toxicity or disease progression may be 
replaced. 
Pharmacokinetics of PLX2853 and Abiraterone 
PLX2853 and abiraterone PK data will be analyzed in each dosing cohort for maximum 
observed concentration (Cmax), AUC, and accumulation at steady state and compared with 
prior dose levels. The number of subjects at a given dose level may be increased as a 
result of the review of safety, observed or anticipated disease activity, and PK data. 
Additional dosing schedules of PLX2853 may be studied, such as alternate day dosing 
(e.g., every other day) depending on emerging safety and PK data. 
 
PLX2853 + Olaparib Combination – Ph1b/2a Study Design 
This multicenter, open label 2-part study will evaluate the safety, PK, PD, and efficacy of 
PLX2853 + olaparib combination therapy in subjects with deleterious or suspected 
deleterious germline or somatic homologous recombination repair (HRR) gene-mutated 
mCRPC who have progressed, as documented by radiographic imaging, prostate-specific 
antigen (PSA), or clinical assessment, following prior treatment with abiraterone acetate 
and prednisone or with enzalutamide. This combination will only be investigated in 
regions where olaparib is approved. 
The study schema is presented below. 
 
 
Phase 1b:  Dose Escalation 
In Phase 1b, the safety profile, RP2D/MTD, PK, and PD of PLX2853 (administered 
orally once daily) in combination with olaparib (administered orally twice daily) in 
21-day treatment cycles will be evaluated. Each cohort will be enrolled and assessed 
using a standard “3+3” design. The rules for determining DLT and dose escalation are 
defined further below. 

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The provisional dose escalation plan is detailed as follows: 
Provisional PLX2853 Dose Escalation Plan 
Dose Level 
PLX2853 Dose 
(mg/day)a 
Olaparib 
(total mg/day)b 
-1 
20 
600  
1 
40 
600  
2 
80 
600  
a 
Once daily (QD) dosing schedule unless otherwise specified. Initial cohort will assess 
QD dosing. Subsequent cohorts may evaluate alternative dosing regimens as agreed 
to by the Study Committee. 
b 
300 mg twice daily (BID) dosing schedule. 
 
DLTs will be assessed in the first 21-day treatment cycle. In the absence of a DLT and in 
conjunction with review of the safety, PK, and available PD data from each cohort by the 
Study Committee, dose escalation is planned to occur in the following manner: 
• 
A minimum of 3 to 4 subjects will be initially enrolled in Dose Level 1 (Cohort 1). If 
a DLT is observed in 1 subject in a given cohort, up to 6 subjects will be treated at 
that dose. 
• 
If DLTs are observed in 2 or more subjects (or ≥33% of the cohort) at a dose level, 
the dose at which this occurs will be considered intolerable and the MTD to have 
been exceeded. The highest dose level at which 0 or 1 of 6 subjects experience a 
DLT will be declared the RP2D. 
• 
If Dose Level 1 is not tolerated, Dose Level -1 (20 mg/day) will be studied. If that 
dose level is intolerable, the study will be halted. 
• 
At least 6 subjects must be evaluable at a given dose level in order to be considered 
an RP2D.  
• 
An RP2D may be declared at a dose level without reaching an MTD if further dose 
escalation is deemed unwarranted. 
• 
Any subject who misses more than 25% of doses in Cycle 1 (e.g., ≥6 doses of 
PLX2853 in 21 days) for reasons other than a treatment-related AE, or is withdrawn 
from the study prior to completing Cycle 1 for reasons other than a DLT, will not be 
DLT evaluable and additional subject(s) may be enrolled to provide adequate data for 
dose escalation decision making. 
After dosing has been completed in each cohort, safety, PK data, and PD data (if 
available) will be reviewed, and dose escalation decisions will be made by the Study 
Committee. Dose escalation decisions will also take into consideration safety information 
beyond the DLT period from earlier cohorts. If no DLT is observed, the recommended 
dose for further evaluation may be established based on toxicity, PK, convenience of 
dosing, and PD (if available) in subjects treated at that dose. Dose escalation will only be 
permitted if adequate safety and tolerability have been demonstrated at the previous lower 
dose for 21 days. Once all ongoing subjects in a dose cohort have been treated for at least 
two 21-day cycles and the safety and tolerability of that dose level has been established, 
intra-subject dose escalation to that dose level may be permitted for subjects enrolled at 
lower dose levels who have not experienced a Grade 3 or higher treatment-related toxicity 
and have completed 2 cycles of PLX2853. Any intra-subject dose escalation requires a 
discussion and agreement with the Medical Monitor. 
Phase 2a:  Dose Expansion 
In Phase 2a (dose expansion), efficacy as well as additional safety, PK, and PD 
information of PLX2853 in combination with olaparib at the RP2D dose established in 
Phase 1b by the Study Committee will be obtained using a Simon’s 2-stage design. 

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Initially, 28 subjects will be enrolled to assess for efficacy in Phase 2a. If 16 or more 
responses are observed in the first 28 evaluable subjects, an additional 30 evaluable 
subjects will be enrolled. Subjects in Phase 2a who do not complete their 12-week disease 
response assessment for reasons other than toxicity or disease progression may be 
replaced. 
Pharmacokinetics of PLX2853 and Olaparib 
PLX2853 and olaparib PK data will be analyzed in each dosing cohort for maximum 
observed concentration (Cmax), AUC, and accumulation at steady state and compared with 
prior dose levels. The number of subjects at a given dose level may be increased as a 
result of the review of safety, observed or anticipated disease activity, and PK data. 
Additional dosing schedules of PLX2853 may be studied, such as alternate day dosing 
(e.g., every other day) depending on emerging safety and PK data. 
Number of Subjects: 
Up to 110 evaluable subjects will be enrolled in the study, as follows. 
 
PLX2853 + Abiraterone Acetate + Prednisone Combination 
 
Phase 1b:  Up to 15 evaluable subjects 
Approximately 9 to 15 evaluable subjects with mCRPC who develop disease 
progression while currently receiving initial treatment with abiraterone acetate and 
prednisone 
 
Phase 2a:  Up to 19 evaluable subjects 
There will be a single Simon’s 2-stage design cohort of between 9 to 19 evaluable 
subjects with mCRPC who develop disease progression while currently receiving 
initial treatment with abiraterone acetate and prednisone 
 
PLX2853 + Olaparib Combination 
 
Phase 1b:  Up to 18 evaluable subjects 
Approximately 9 to 18 evaluable subjects, with deleterious or suspected deleterious 
germline or somatic homologous recombination repair (HRR) gene-mutated mCRPC 
who have progressed following prior treatment with abiraterone acetate or 
enzalutamide. 
 
Phase 2a:  Up to 58 evaluable subjects 
There will be a single Simon’s 2-stage design cohort of between 28 to 58 evaluable 
subjects with deleterious or suspected deleterious germline or somatic homologous 
recombination repair (HRR) gene-mutated mCRPC who have progressed following 
prior treatment with abiraterone acetate or enzalutamide 
Inclusion Criteria: 
Inclusion Criteria Applicable to Both Combinations: 
1. Age ≥18 years at the time of signing informed consent. 
2. Histologically confirmed adenocarcinoma of the prostate with tumor tissue available 
for molecular analyses. 
3. Serum testosterone level of <50 ng/dL (<2.0 nM) assessed within 28 days of C1D1 
and surgically or medically castrated and/or receiving treatment with an 
LHRH/GnRH analogue (agonist/antagonist). 
4. Subjects must continue primary androgen deprivation with an LHRH/GnRH 
analogue (agonist/antagonist) or have received an orchiectomy. If receiving primary 
androgen deprivation therapy, this therapy must have been initiated at least 28 days 
prior to start of study dosing and must be continued throughout the study. 
5. Eastern Cooperative Oncology Group Performance Status 0 to 1. 

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6. Adequate organ function as demonstrated by the following laboratory values. All 
Screening laboratory tests should be performed within 10 days prior to the first 
PLX2853 dose. 
 
Hematological: 
 
Neutrophils ≥1500/µL. 
 
Platelets ≥100,000/µL (transfusion not permitted within 28 days prior to 
screening blood draw for olaparib, 14 days for abiraterone). 
 
Hemoglobin ≥9 g/dL (transfusion and erythropoietin not permitted within 
28 days prior to screening blood draw for olaparib, 14 days for abiraterone). 
 
Renal: 
 
Measured (by 24-hour urine collection) or calculated Creatinine Clearance 
(CrCL) >50 mL/min. The Cockcroft-Gault formula should be used for 
calculation (Appendix 1). 
 
Hepatic: 
 
Serum total bilirubin ≤1.5 × upper limit of normal (ULN). 
Exception for elevated bilirubin secondary to Gilbert’s disease. 
Confirmation of Gilbert’s diagnosis requires:  elevated unconjugated 
(indirect) bilirubin values; normal complete blood count in previous 
12 months, blood smear, and reticulocyte count; normal aminotransferases 
and alkaline phosphatase in previous 12 months. 
 
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
≤2 × ULN. 
For subjects with metastatic liver metastases ≤2.5 × ULN. 
 
Coagulation: 
 
International normalized ratio (INR) ≤1.5 × ULN. 
 
Activated partial thromboplastin time (aPTT) ≤1.5 × ULN. 
 
Chemistry: 
 
Albumin ≥3.0 g/dL. 
7. Fertile male subjects with female sexual partners must agree to use a highly effective 
method of birth control (defined in Section 4.2.1) during the study and for 90 days 
after the last dose of study drug. 
8. Except as specified above for organ function, all drug-related toxicity from previous 
cancer therapy (including ongoing abiraterone acetate + prednisone therapy if 
applicable) must be resolved (to Grade ≤1 or baseline per National Cancer Institute 
Common Terminology Criteria for Adverse Events version 5.0) prior to study 
treatment administration (Grade 2:  alopecia, hot flashes, decreased libido, or 
neuropathy is allowed). 
9. Willingness and ability to provide written informed consent prior to any study-related 
procedures and to comply with all study requirements. 
 
Inclusion Criteria Applicable to PLX2853 + Abiraterone Acetate + Prednisone 
Combination: 
10. Currently receiving initial abiraterone acetate 1000 mg QD and prednisone per 
abiraterone acetate label as most recent systemic therapy for mCRPC and showing 
evidence of progression as assessed by the investigator with one or more of the 
following (Subjects who begin treatment in the hormone sensitive setting and 
progress to mCRPC and have not discontinued their initial abiraterone acetate 
treatment are not excluded). Subjects must be on a stable dose of prednisone for at 
least 14 days prior to C1D1: 

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a. 
PSA progression defined, per PCWG3 criteria (Scher 2016; Appendix 6) at trial 
entry, as ≥2 occurrences of rising PSA levels with a minimum interval of 1 week 
and a PSA concentration of ≥1 ng/mL if confirmed PSA rise is the only measure 
of progression. 
b. Worsening measurable disease on CT/MRI per RECIST v1.1 criteria or at least 
one new documented bone lesion on a bone scan. 
11. Potassium within normal limits. 
 
Inclusion Criteria Applicable to PLX2853 + Olaparib Combination: 
12. Prior genetic testing completed with known deleterious or suspected deleterious 
germline or somatic homologous recombination repair (HRR) gene-mutation per 
FDA label for mCRPC as defined by an FDA-approved companion diagnostic (HRR 
mutation must be known prior to consent). 
13. Prior treatment with abiraterone acetate and/or enzalutamide for metastatic prostate 
cancer and/or CRPC. 
14. Evidence of radiographic progression of metastatic disease at study entry as assessed 
by the investigator defined as measurable disease on CT/MRI per RECIST v1.1 
criteria or at least one documented bone lesion on a bone scan. Subjects whose 
disease spread is limited to regional pelvic lymph nodes or local recurrence 
(e.g., bladder, rectum) are not eligible. 
Exclusion Criteria: 
Exclusion Criteria Applicable to Both Combinations: 
1. Prior exposure to a bromodomain inhibitor. 
2. Ongoing systemic infection requiring antibiotic, antiviral, or antifungal treatment. 
3. History of autoimmune hemolytic anemia or autoimmune thrombocytopenia. 
4. Presence of symptomatic or uncontrolled central nervous system or leptomeningeal 
metastases. 
Note:  Subjects with stable, treated brain metastases are eligible for this study. 
However, subjects must not have required steroid treatment for their brain metastases 
within 30 days of Screening. 
5. Symptomatic or impending cord compression unless appropriately treated beforehand 
and clinically stable and asymptomatic. 
6. Known or suspected allergy to the investigational agent or any agent given in 
association with this study. 
7. Clinically significant cardiac disease, defined as any of the following: 
 
Clinically significant cardiac arrhythmias including bradyarrhythmias and/or 
subjects who require anti-arrhythmic therapy (excluding beta blockers or 
digoxin). Subjects with controlled atrial fibrillation are not excluded. 
 
Congenital long QT syndrome or subjects taking concomitant medications 
known to prolong the QT interval (Drugs with a low risk of QTc prolongation 
that are needed for infection control or nausea may be permitted with approval 
from the Medical Monitor). A list of drugs known to prolong the QT interval and 
risk of TdP can be found in Appendix 4. 
 
QTcF ≥450 msec at Screening (based on average of triplicate ECGs at baseline). 
o 
If the QTc is prolonged in a subject with a pacemaker or bundle branch 
block, the subject may be enrolled in the study if confirmed by the medical 
monitor. 
 
History of clinically significant cardiac disease or congestive heart failure 
>New York Heart Association Class II or left ventricular ejection fraction 
measurement of <50% at baseline. Subjects must not have unstable angina 

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(anginal symptoms at rest) or new-onset angina within the last 3 months or have 
had a coronary artery bypass, angioplasty, vascular stent, or myocardial 
infarction within the past 6 months. 
 
Uncontrolled hypertension, defined as systolic blood pressure >160 mmHg or 
diastolic blood pressure >100 mmHg which has been confirmed by 2 successive 
measurements despite optimal medical management. 
 
Arterial or venous thrombotic or embolic events such as cerebrovascular 
accident (including transient ischemic attacks), deep vein thrombosis, or 
pulmonary embolism within the 3 months before start of study medication 
(except for adequately treated catheter-related venous thrombosis occurring 
>1 month before the start of study medication). 
8. Inability to take oral medication or significant nausea and vomiting, malabsorption, 
or significant small bowel resection that, in the opinion of the Investigator, would 
preclude adequate absorption. 
9. Non-healing wound or ulcer. 
10. Infection with HIV-1 or HIV-2. Exception:  subjects with well-controlled HIV 
(e.g., CD4 >350/mm3 and undetectable viral load) are eligible. 
11. Current active liver disease from any cause, including hepatitis A (hepatitis A virus 
immunoglobulin M positive), hepatitis B (hepatitis B virus [HBV] surface antigen 
positive), or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by 
HCV ribonucleic acid). Subjects with HCV with undetectable virus after treatment 
are eligible. Subjects with a prior history of HBV are eligible if quantitative PCR for 
HBV DNA is negative. These subjects must be willing to undergo additional testing 
per local standard of care. 
12. Baseline moderate or severe hepatic impairment (Child-Pugh Class B and C). 
13. Active known second malignancy with the exception of any of the following: 
 
Adequately treated basal cell carcinoma or squamous cell carcinoma of the skin. 
 
Adequately treated Stage I cancer from which the subject is currently in 
remission and has been in remission for ≥2 years. 
 
Any other cancer from which the subject has been disease-free for ≥3 years. 
14. Major surgery or significant traumatic injury within 28 days of Cycle 1 Day 1. 
15. Currently receiving medications known to be strong or moderate inducers or 
inhibitors of CYP3A4 and substrates of CYP2D6 with a narrow therapeutic window 
(Appendix 2). These strong and moderate inducers, inhibitors and substrates must be 
discontinued at least 7 days prior to the first administration of study drug). 
16. Use of biotin (i.e., Vitamin B7) or supplements containing biotin higher than the 
daily adequate intake of 30 µg (NIH-ODS 2020). Note:  Subjects who switch from a 
high dose to a dose of 30 µg/day or less are eligible for study entry. 
17. Any chronic medical condition requiring a dose of corticosteroids greater than 10 mg 
prednisone/prednisolone daily. 
18. Use of herbal, alternative and food supplements (i.e., PC-Spes, Saw Palmetto, 
St. John’s Wort, etc.) and probiotics must be discontinued before treatment start. 
Daily Multi-vitamin (provided it does not contain biotin >30 µg/day), calcium, and 
Vitamin D are permitted. 
19. Subjects with a history of adrenal insufficiency, hyperaldosteronism, or pituitary 
dysfunction. 

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20. Poorly controlled known type 2 diabetes with HbA1C >7.5% (must be assessed 
within 28 days of C1D1 for all subjects with known type 2 diabetes). 
21. Live vaccine within 4 weeks of starting treatment. 
22. Treatment with warfarin within 7 days of C1D1. 
23. Subject is participating in any other therapeutic clinical study (observational or 
registry studies are allowed). 
24. Presence of any other medical, psychological, familial, sociological, or geographic 
condition potentially hampering compliance with the study protocol or would 
interfere with the study endpoints or the subject’s ability to participate in the study in 
the judgment of the Investigator. 
 
Exclusion Criteria Applicable to PLX2853 + Abiraterone Acetate + Prednisone 
Combination: 
25. Receipt of any anti-cancer therapy prior to Cycle 1 Day 1 with the exception of 
abiraterone acetate and GnRH therapy: 
 
Prior systemic chemotherapy in the setting of mCRPC is not permitted (prior 
chemotherapy in the hormone-sensitive setting is allowed provided last dose was 
at least 6 months prior to Cycle 1 Day 1). Prior chemotherapy for any other 
disease within 2 years is prohibited. 
 
Radiation therapy within 14 days prior to Cycle 1 Day 1. 
 
Small molecule anti-cancer therapy for the treatment of cancer within 14 days or 
5 half-lives (whichever is shorter) prior to Cycle 1 Day 1. 
 
Immunotherapy or other biologic therapy (e.g., monoclonal antibodies, antibody-
drug conjugates) for the treatment of cancer within 21 days or 5 half-lives 
(whichever is shorter) prior to Cycle 1 Day 1. 
 
5-α reductase inhibitors (e.g., finasteride, dutasteride), estrogen compounds 
(including estramustine) and megesterol are considered to be anti-cancer agents 
and prohibited within 21 days or 5 half-lives (whichever is shorter) prior to 
Cycle 1 Day 1. 
Note:  Subjects can receive a stable dose of bisphosphonates or denosumab for bone 
metastases before and during the study, as long as these were started at least 4 weeks 
prior to treatment with study drug. 
 
Exclusion Criteria Applicable to PLX2853 + Olaparib Combination: 
26. A medical history that includes any of myelodysplastic syndrome, monoclonal 
gammopathy of undetermined significance or acute myeloid leukemia. 
27. Receipt of any anti-cancer therapy prior to Cycle 1 Day 1 with the exception of 
GnRH therapy: 
 
Radiation therapy within 14 days prior to Cycle 1 Day 1. 
 
Small molecule anti-cancer therapy for the treatment of cancer within 14 days or 
5 half-lives (whichever is shorter) prior to Cycle 1 Day 1. 
 
Immunotherapy or other biologic therapy (e.g., monoclonal antibodies, antibody-
drug conjugates) for the treatment of cancer within 21 days or 5 half-lives 
(whichever is shorter) prior to Cycle 1 Day 1. 
 
5-α reductase inhibitors (e.g., finasteride, dutasteride), estrogen compounds 
(including estramustine) and megesterol are considered to be anti-cancer agents 
and prohibited within 21 days or 5 half-lives (whichever is shorter) prior to 
Cycle 1 Day 1. 

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 
Prior treatment with DNA-damaging cytotoxic chemotherapy (including 
platinum-based agents, cyclophosphamide, and mitoxantrone) is excluded with 
the exception of estramustine. Non-DNA-damaging chemotherapy (docetaxel, 
cabazetaxel, etc.) within 14 days or 5 half-lives (whichever is shorter) is 
excluded. Any chemotherapy not listed requires Medical Monitor review and 
approval to confirm eligibility. 
Note:  Subjects can receive a stable dose of bisphosphonates or denosumab for bone 
metastases before and during the study as long as these were started at least 4 weeks 
prior to treatment with study drug. 
28. Prior exposure to a PARP inhibitor. 
Duration of Study: 
Screening: 
 
Up to 28 days prior to the first dose of study drug 
Treatment Period: 
 
Daily in 21-day treatment cycles until subject discontinuation or withdrawal or study 
termination 
30-Day Follow-Up Visit: 
 
Approximately 30 days after the last dose of study drug or prior to starting any new 
anti-cancer therapy, whichever occurs first. 
Long-Term Follow-Up Visits: 
 
Subjects will be followed until death, withdrawal of consent, or loss to follow-up 
according to the following schedule: 
 
First two years after the 30-day FU Visit – Every 3 months 
 
Third year after the 30-day FU Visit and beyond – Every 6 months 
 
Survival follow-up can be via clinic visit, phone call to the subject or referring 
physician, or other method deemed appropriate by the site and should assess survival, 
progression, subsequent therapy, and response 
 
Any subject with a confirmed response who discontinues treatment for reasons other 
than disease progression will continue to be followed per standard of care and no less 
than every 3 months until documented disease progression, initiation of a new anti-
cancer treatment, or 1 year from discontinuation of study treatment. Response 
assessment during follow-up will include at minimum the modality used to determine 
response (radiographic imaging, PSA, and/or CTC assessment). 
Test Products, Doses, 
and Mode of 
Administration: 
PLX2853 
PLX2853 is formulated as 20-mg strength tablets for oral use. Subjects should fast for 
2 hours before and 1 hour after taking PLX2853. Doses will be taken orally with water. 
PLX2853 should be taken at approximately the same time each day. PLX2853 tablets 
should be swallowed whole and not crushed, chewed, or dissolved in water. A dosing 
period of up to 30 minutes is permissible if required by the number of tablets to be taken 
or as convenient for the subject. 
Abiraterone Acetate 
Abiraterone acetate 1000 mg is administered orally once daily in combination with 
prednisone 5 mg administered orally twice daily. Abiraterone acetate (ZYTIGA® or 
generic equivalent) is available as either 500 mg film-coated tablets or 250 mg uncoated 
tablets. Abiraterone acetate must be taken on an empty stomach. No food should be 
consumed for at least 2 hours before the dose of abiraterone acetate is taken and for at 
least 1 hour after the dose of abiraterone acetate is taken. The tablets should be swallowed 
whole with water and not be crushed or chewed. Please refer to the ZYTIGA® FDA label 
or SmPC for additional information. 
PLX2853 and abiraterone acetate should be taken at the same time. 
 

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Prednisone 
Prednisone 5 mg tablets are administered per the label for abiraterone acetate. Prednisone 
is recommended to be taken with food or milk at least 2 hours before PLX2853 and 
abiraterone acetate or 1 hour after taking PLX2853 and abiraterone acetate, except for PK 
collection days when subjects should take prednisone with food or milk at least 1 hour 
after taking PLX2853 and abiraterone acetate. An equivalent approved steroid may be 
used where applicable (prednisolone is acceptable; other equivalent agents must be 
approved by the Plexxikon Medical Monitor). 
Olaparib 
Olaparib 300 mg is administered orally twice daily. The morning dose of olaparib should 
be taken at the same time as PLX2853 and subjects should fast for at least 2 hours before 
and 1 hour after taking PLX2853 and olaparib. The evening olaparib dose may be taken 
with or without food. The tablets should be swallowed whole with water and not be 
chewed, crushed, dissolved, or divided. Olaparib tablets are available in 2 strengths, 
100 mg and 150 mg. Please refer to the LYNPARZA® FDA label for additional 
information. 
PLX2853 and olaparib (morning dose) should be taken at the same time. 
Definition of 
Dose-limiting 
Toxicity (DLT) 
(Phase 1b PLX2853, 
abiraterone acetate, 
and/or prednisone, 
and Phase 1b 
PLX2853 and/or 
olaparib) 
DLTs are defined as clinically significant AEs or laboratory abnormalities occurring 
during the first cycle (21 days) of study drug administration that are at least possibly 
related to any study drug (PLX2853, abiraterone acetate, olaparib, or prednisone), and 
that meet one of the following CTCAE v5.0 criteria below. DLTs will be evaluated for 
each cohort. DLTs will be assessed during a DLT assessment window of 21 days in 
Cycle 1. Toxicities occurring in treatment Cycle 2 or later will be reviewed and their 
impact on dose escalation and dosing frequency assessed. If during the DLT window a 
subject requires treatment with a concomitant medication that results in a dose reduction 
of abiraterone acetate or olaparib (per their label), the patient will be considered 
inevaluable, unless the AE requiring treatment meets the definition of a DLT. 
In Phase 1, a subject who misses greater than 25% of their expected doses in Cycle 1, or 
does not complete Cycle 1, for reasons other than a related toxicity will be considered 
inevaluable and may be replaced. 
DLTs will be determined based on the following criteria: 
Hematologic Toxicities 
• 
Grade 4 neutropenia lasting >5 days 
• 
Febrile neutropenia 
• 
Grade 4 thrombocytopenia of any duration 
• 
Grade ≥3 thrombocytopenia associated with clinically significant hemorrhage for any 
duration 
• 
Grade 4 anemia 
Non-Hematologic Toxicities 
• 
A dose reduction required during Cycle 1 due to an AE (except as specified above) 
• 
AE related treatment delays causing a subject to miss at least 25% of their total 
expected doses of any drug in the combination during Cycle 1 
• 
Any Grade ≥3 non-hematologic toxicity of any duration, except: 
▪ 
Grade 3 nausea, vomiting, or diarrhea and Grade 4 vomiting or diarrhea in the 
absence of maximal medical therapy that resolves in 72 hours 
▪ 
Grade 3 fatigue lasting <5 days 
▪ 
Grade 3 hypertension that can be controlled with medical therapy 
▪ 
An increase of indirect (unconjugated) bilirubin indicative of 
M. Meulengracht/Gilbert’s syndrome 

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▪ 
Serum lipase and/or serum amylase Grade 3 ≤7 consecutive days without clinical 
signs or symptoms of pancreatitis 
▪ 
Grade 3 AST/ALT for <5 days 
▪ 
Grade 3 neuropathy in subjects with pre-existing Grade 2 neuropathy 
• 
ALT/AST >3 x ULN with total bilirubin >2 x ULN without another explanation 
(e.g., cholestasis) 
• 
Any Grade 3 clinically significant electrolyte imbalance confirmed with repeat 
assessment within 24 hours. 
A subject who experiences a DLT may remain in the study and continue receiving 
PLX2853, abiraterone acetate, and prednisone or PLX2853 and olaparib at a lower dose if 
the Investigator deems the potential benefit outweighs the risk and that the subject is not 
eligible for, and/or interested in, an alternative therapy after agreement by the Medical 
Monitor. If a subject is required to permanently discontinue at least one of the study 
medications for any reason they will be discontinued from all study treatment. For 
patients receiving abiraterone acetate, if PLX2853 and abiraterone acetate are withheld, 
then consideration should be given to tapering the dose of prednisone as clinically 
indicated. 
AEs occurring in treatment Cycle 2 or later will be collected, analyzed, and discussed 
with the Study Committee to help inform the selection of doses for subsequent study 
cohorts, including the option of dose reduction. If cumulative toxicities (e.g., AEs 
meeting the criteria of a DLT occurring in Cycle 2 or later) are observed requiring dose 
reductions, dose escalation may be halted and more subjects may be treated at that or a 
lower dose level.  
Pharmacokinetic 
Parameters: 
The PK parameters of PLX2853 and abiraterone or olaparib will be assessed by 
measuring the AUC from time zero to time of last measurable concentration postdose 
(AUC0-last), AUC from time zero to 24 hours postdose (AUC0-24), AUC from time zero 
extrapolated to infinite time (AUC0-∞), Cmax, time to Cmax (Tmax), terminal elimination 
half-life (T1/2), and accumulation ratio at steady state. 
Dose proportionality following study dosing will be explored by analyzing natural 
log -transformed PK variables, AUC0-last, AUC0-24, AUC0-∞, and Cmax, with a linear model 
including the natural log-transformed dose as a covariate.  
Biomarker and 
Pharmacodynamic 
(PD) Parameters: 
Biomarker analyses for PD include, but are not limited to: 
• 
Gene expression, nucleic acid sequencing, histochemical and/or protein analyses of 
plasma, peripheral blood cells, and/or tumor tissue. 
• 
Analysis of CTC status and possibly other exploratory markers of response or 
resistance. 
Exploratory analysis of biomarker samples may also be performed to learn about the drug 
and disease properties. 
Efficacy Parameters: Treatment response will be defined as: 
• 
Objective response by RECIST v1.1 with a minimum interval for confirmation of CR 
and PR of 4 weeks and/or 
• 
PSA decline of ≥50% from baseline, confirmed by a second consecutive PSA 
assessment at least 3 weeks later 
• 
Conversion of circulating tumor cell count (CTC) to <5 cells/7.5 mL blood nadir 
confirmed by an additional assessment at least 3 weeks later (for subjects with a CTC 
count of ≥5 cells/7.5 mL blood at baseline) 
Treatment failure will be defined as: 
• 
Progression by RECIST v1.1 and/or 
• 
Progression by bone scan with a confirmatory scan ≥6 weeks later and/or 

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• 
PSA progression per PCWG3 (Scher 2016) (a ≥25% increase and an absolute 
increase of ≥2 ng/mL above the nadir, occurring at least 12 weeks from start of 
treatment, and confirmed by a second consecutive value obtained at least three weeks 
later). PSA progression alone does not necessitate treatment discontinuation. 
The last value of PSA, CTC count, CT scan, and bone scan before the date of first study 
treatment (within 28 days for imaging; within 10 days for laboratory assessments) will be 
used as the baseline value for this assessment. 
In addition, the following parameters will be assessed: 
• 
Radiographic progression-free survival (rPFS) 
• 
Time to PSA progression 
• 
Duration of PSA response 
• 
Overall survival 
• 
PK parameters of PLX2853 and abiraterone and PLX2853 and olaparib following 
single and repeated dosing 
• 
Best Overall Response (BOR) per RECIST v1.1 
• 
Duration of Response (DOR) 
• 
Time to first Symptomatic Skeletal-Related Event (SSRE)  
Safety Parameters: 
Safety variables to be assessed will include assessment of AEs, physical examinations, 
laboratory test results (hematology, clinical chemistry, coagulation, serum inflammation 
markers, and urinalysis), electrocardiogram, MUGA/ECHO, weight, and vital signs. 
Endpoints: 
PLX2853 + Abiraterone Acetate + Prednisone Combination 
Phase 1b, Primary Endpoint: 
• 
Incidence of DLTs, TEAEs, changes in safety parameters, and unacceptable 
toxicities 
Phase 2a, Primary Endpoint: 
• 
Response as defined by any of the outcomes listed below. If any of these occur, the 
subject will be considered to have responded. 
▪ 
Objective response by per RECIST v1.1 with a minimum interval for 
confirmation of CR and PR of 4 weeks 
▪ 
PSA decline of ≥50% from baseline, confirmed by a second consecutive PSA 
assessment at least 3 weeks later 
▪ 
Conversion of circulating tumor cell count (CTC) to <5 cells/7.5 mL blood nadir 
confirmed by an additional assessment at least 3 weeks later (for subjects with a 
CTC count of ≥5 cells/7.5 mL blood at baseline) 
 
PLX2853 + Olaparib Combination 
Phase 1b, Primary Endpoint: 
• 
Incidence of DLTs, TEAEs, changes in safety parameters, and unacceptable 
toxicities 
Phase 2a, Primary Endpoint: 
• 
Response as defined by any of the outcomes listed below. If any of these occur, the 
subject will be considered to have responded. 
▪ 
Objective response by modified RECIST v1.1 with a minimum interval for 
confirmation of CR and PR of 4 weeks 
▪ 
PSA decline of ≥50% from baseline, confirmed by a second consecutive PSA 
assessment at least 3 weeks later 

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▪ 
Conversion of circulating tumor cell count (CTC) to <5 cells/7.5 mL blood nadir 
confirmed by an additional assessment at least 3 weeks later (for subjects with a 
CTC count of ≥5 cells/7.5 mL blood at baseline) 
 
Secondary Endpoints – Both Phases, Both Combinations 
• 
Radiographic progression-free survival (rPFS) 
• 
Time to PSA progression 
• 
Duration of PSA response 
• 
Overall survival defined as the time from the first dose of study drug to the date of 
death due to any cause 
• 
Incidence of TEAEs, changes in safety parameters, and unacceptable toxicities 
• 
PK parameters of PLX2853 and abiraterone and PLX2853 and olaparib following 
single and repeated dosing 
• 
BOR per RECIST v1.1 
• 
DOR (time from date of first documented, confirmed response using RECIST v1.1 
and PCWG3 until date of documented progression or death from any cause). 
• 
Time to first SSRE defined as: 
▪ 
Use of radiation therapy to prevent or relieve skeletal symptoms. 
▪ 
Occurrence of new symptomatic pathological bone fractures (vertebral or non-
vertebral). Radiologic documentation is required. 
▪ 
Occurrence of spinal cord compression. Radiologic documentation required. 
▪ 
Orthopedic surgical intervention for bone metastasis. 
 
Exploratory Endpoints – Both Phases, Both Combinations 
• 
Analysis of peripheral blood cells for dose- and exposure-dependent changes in the 
expression of BET target genes as measured by a 12-gene BET inhibitor responsive 
signature 
• 
Pharmacodynamic assessments for potential biomarkers 
Statistical 
Considerations: 
Phase 1b (PLX2853 + Abiraterone Acetate + Prednisone Combination and 
PLX2853 + Olaparib Combination): 
Both combinations will be evaluated in Phase 1b using a standard “3+3” design in order 
to determine the MTD/RP2D taking into consideration safety, PK, and PD data (if 
applicable). 
Data will be tabulated and evaluated by descriptive statistics. Statistical analyses for the 
primary objectives will be descriptive only, with no hypothesis testing. Summary tables 
will present results for each dose cohort. Descriptive statistics will be presented for 
continuous variables, and frequencies and percentages will be presented for categorical 
and ordinal variables. 
 
Phase 2a (PLX2853 + Abiraterone Acetate + Prednisone Combination): 
Efficacy of PLX2853 + abiraterone acetate + prednisone will be investigated in a cohort 
of subjects with mCRPC. Phase 2a will enroll up to 19 evaluable subjects using a Simon’s 
2-stage design in which initially 9 evaluable subjects are enrolled. If 2 or more responders 
are observed in 9 evaluable subjects, another 10 evaluable subjects will be enrolled for a 
total of 19 subjects. If 6 or more responders are observed, the study has 80% power with 
alpha of 0.05 to reject the RR of 15% in favor of the RR of 40%. Recruitment will stop if 
no more than 1 responder is observed after the initial 9 subjects have been accrued. ORR 

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will be summarized along with a 95% confidence interval (CI). A 2-sided 95% CI will be 
calculated for the true response rate based on the Clopper-Pearson method. 
Response will be defined on the basis of the following outcomes, if any of these occur 
subjects will be considered to have responded: 
• 
Objective response by RECIST v1.1 with a minimum interval for confirmation of CR 
and PR of 4 weeks and/or 
• 
PSA decline of ≥50% from baseline, confirmed by a second consecutive PSA 
assessment at least 3 weeks later 
• 
Conversion of circulating tumor cell count (CTC) to <5 cells/7.5 mL blood nadir 
confirmed by an additional assessment at least 3 weeks later (for subjects with a CTC 
count of ≥5 cells/7.5 mL blood at baseline) 
Safety, PK, and PD data will be tabulated and evaluated by descriptive statistics. 
Statistical analyses for the primary objectives will be descriptive only, with no hypothesis 
testing. Summary tables will present results for each dose cohort. Descriptive statistics 
will be presented for continuous variables, and frequencies and percentages will be 
presented for categorical and ordinal variables. 
 
Phase 2a (PLX2853 + Olaparib): 
Efficacy of PLX2853 + olaparib will be investigated in a cohort of subjects with mCRPC. 
Phase 2a will enroll up to 58 evaluable subjects using a Simon’s 2-stage design in which 
initially 28 evaluable subjects are enrolled. If 16 or more responders are observed in 
28 evaluable subjects, another 30 evaluable subjects will be enrolled for a total of 
58 subjects. If 38 or more responders are observed, the study has 80% power with alpha 
of 0.05 to reject the RR of 54% in favor of the RR of 70%. Recruitment will stop if no 
more than 15 responders are observed after the initial 28 subjects have been accrued. 
ORR will be summarized along with a 95% confidence interval (CI). A 2-sided 95% CI 
will be calculated for the true response rate based on the Clopper-Pearson method. 
Response will be defined on the basis of the following outcomes, if any of these occur 
subjects will be considered to have responded: 
• 
Objective response by RECIST v1.1 and/or 
• 
PSA decline of ≥50% from baseline, confirmed by a second consecutive PSA 
assessment at least 3 weeks later 
• 
Conversion of circulating tumor cell count (CTC) to <5 cells/7.5 mL blood nadir 
confirmed by an additional assessment at least 3 weeks later (for subjects with a CTC 
count of ≥5 cells/7.5 mL blood at baseline) 
Safety, PK, and PD data will be tabulated and evaluated by descriptive statistics. 
Statistical analyses for the primary objectives will be descriptive only, with no hypothesis 
testing. Summary tables will present results for each dose cohort. Descriptive statistics 
will be presented for continuous variables, and frequencies and percentages will be 
presented for categorical and ordinal variables. 
 

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SYNOPSIS TABLE 1:  PHASE 1B PLX2853 + ABIRATERONE/PREDNISONE OR PLX2853 + OLAPARIB DOSE ESCALATION 
SCHEDULE OF EVENTS 
ASSESSMENTS▼ PROCEDURE▼ 
SCR1 
C1 
C2 
C3 
C4+2 
30-day 
FU3 
LTFU 
 
STUDY DAY► -28 to -1 
1 
2 
8 
15 
1 
15 
1 
1 
 
WINDOW (days)► 
 
 
 
± 2 
± 2 
+ 3 
± 3 
± 5 
± 5 
± 7 
± 14 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
History 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Identification of HRR Defect (Olaparib only; historical 
testing)4 
X 
 
 
 
 
 
 
 
 
 
 
Vital 
Vital signs5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
Safety 
Physical exam6 
X 
X7 
 
X 
X 
X 
X 
X 
X 
X 
 
ECOG 
X 
X7 
 
X 
X 
X 
X 
X 
X 
X 
 
12-lead ECG8,18 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
ECHO or MUGA (abiraterone only)9 
X 
 
 
 
 
 
 
 
 
 
 
Lab 
PG sample 
X 
 
 
 
 
 
 
 
 
 
 
Hepatitis A, B and C, HIV10 
X1 
 
 
 
 
 
 
 
 
 
 
Hematology11 
X1 
X7 
 
X 
X 
X 
X 
X 
X 
X 
 
Chemistry12 
X1 
X7 
 
X 
X 
X 
X 
X 
X 
X 
 
Coagulation tests13 
X1 
X7 
 
X 
X 
X 
X 
X 
X 
X 
 
Hemoglobin A1c (Type 2 diabetics only) 
X30 
 
 
 
 
 
 
 
 
 
 
Testosterone 
X31 
 
 
 
 
 
 
 
X31 
 
 
PSA 
X1 
X7 
 
 
 
X 
 
X 
X 
X 
 
Circulating Tumor Cells14 
X 
X7 
 
 
 
 
 
 
X22 
X 
X27 
Urinalysis15 
X1 
X7 
 
X 
X 
X 
X 
X 
X 
X 
 
Serum c-reactive protein 
X1 
X7 
 
X 
X 
X 
 
X 
X 
X 
 
PK sample16,17,18 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Biomarker (PD) blood sample19 
 
X 
X 
 
X 
X 
 
X 
X 
X 
 

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ASSESSMENTS▼ PROCEDURE▼ 
SCR1 
C1 
C2 
C3 
C4+2 
30-day 
FU3 
LTFU 
 
STUDY DAY► -28 to -1 
1 
2 
8 
15 
1 
15 
1 
1 
 
WINDOW (days)► 
 
 
 
± 2 
± 2 
+ 3 
± 3 
± 5 
± 5 
± 7 
± 14 
Medications, 
Non-drug 
Treatments, 
Radiotherapy 
Prior treatment 
X 
 
 
 
 
 
 
 
 
 
 
Concomitant Medication Review 
X 
 
AE 
Adverse events20 
X 
 
Treatment Response Archival tissue sample 
X 
 
 
 
 
 
 
 
 
 
 
Paired biopsy for malignant lesion (optional) 
X28 
 
 
 
 
X 
 
 
 
 
 
CT Scan21 
X 
 
 
 
 
 
 
 
X22 
 
X27 
Bone Scan21 
X 
 
 
 
 
 
 
 
X22 
 
X27 
SSRE evaluation 
X 
 
Treatment 
PLX2853 administration16,23 
 
Daily administration for 21 days (full cycle) 
 
 
Abiraterone acetate or olaparib administration16,23 
X29 
Abiraterone:  QD administration for 21 days (full cycle) or 
Olaparib:  BID administration for 21 days (full cycle) 
 
 
Prednisone administration (abiraterone combo only)16,24 
X29 
BID administration for 21 days (full cycle) 
 
 
Study drug compliance (diary review and accountability)25 
 
 
 
X 
X 
X 
X 
 
Survival 
Survival follow-up26 
 
 
 
 
 
 
 
 
 
 
X 
30-day FU = 30-day follow-up visit; AE = adverse event; aPTT = activated partial thromboplastin time; AUC = area under the concentration-time curve; BID = twice daily; 
C = cycle; CTC = circulating tumor cells; D = day; DLT = dose-limiting toxicity; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group;  
INR = international normalized ratio; LTFU = long-term follow-up visit; PD = pharmacodynamics; PG = pharmacogenomics; PK = pharmacokinetic;  
PSA = prostate-specific antigen; PT = prothrombin time; QD = once daily 
1 
Unless otherwise specified, all screening laboratory tests should be performed within 10 days of C1D1. A complete list of required tests is found in Appendix 1 to the protocol. 
2 
If the subject does not have any ongoing Grade 2 or higher treatment-related AEs and following discussion with the Medical Monitor, subjects on treatment longer than 
12 months may be given the option to only have study visits every 2 cycles. 
3 
The 30-day FU visit should occur approximately 30 days after the last dose of PLX2853 or prior to starting any new anti-cancer therapy, whichever occurs first. 
4 
Olaparib combination only:  known HRR status assessed per standard of care testing (FoundationOne CDx or BRACAnalysis CDx are suggested). Results of test must be 
available prior to consent. 
5 
Vital signs must be obtained predose (PLX2853, abiraterone acetate, prednisone, and olaparib) on PK collection days. 
6 
Complete physical examination at Screening and 30-day FU only. All other physical examinations may be abbreviated and symptom-directed. 

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7 
ECOG Performance Status, symptom-directed physical examination, hematology, chemistry, coagulation, urinalysis, C-reactive protein, and PSA do not need to be repeated if 
these assessments from Screening occurred within 3 days of C1D1. CTC count does not need to be repeated if the assessment from Screening occurred within 10 days of 
C1D1 unless the screening sample was unable to be processed or a change in status is suspected. Subjects must continue to meet all eligibility criteria that are repeated at the 
time of initiation of C1D1 dosing. 
8 
All ECGs are single tracings on the specified days and only Screening and predose C1D1 should be done in triplicate (approximately 10 seconds per ECG over a 5-minute 
period). Standard 12-lead ECG with QTcF calculation. Fridericia’s correction is required. QTcF = (QT)/3√(RR). Subjects must continue to meet eligibility criteria on C1D1 
pre-dose assessment in order to proceed with dosing. 
9 
Abiraterone combination only:  ECHO or MUGA will be performed in screening and as clinically indicated once on study. 
10 Serology testing for hepatitis A, B, and C, and HIV should be performed within 28 days of C1D1 if the subject is taking ≤30 µg/day biotin. If the subject is taking >30 µg/day 
biotin, the subject must lower their daily biotin intake to ≤30 µg and wait 14 days before hepatitis A, B, and C serology testing can be performed (elevated levels of biotin may 
interfere with viral serology testing). 
11 Hematology evaluation must include hemoglobin, hematocrit, and white blood cell count with differential and platelet count. A complete list of required tests is found in 
Appendix 1 to the protocol. 
12 Chemistry evaluation must include a complete chemistry panel including liver transaminases, amylase, lipase, and gamma-glutamyl transferase. A complete list of required 
tests is found in Appendix 1 to the protocol. 
13 Coagulation evaluation must include PT/INR, aPTT, fibrinogen, d-dimer, and Factor VII. A complete list of required tests is found in Appendix 1 to the protocol. 
14 Subjects with a positive CTC sample at baseline, as indicated by a value of at least 5 cells/7.5 mL blood, will continue to have CTC samples collected while on treatment at 
each radiographic assessment timepoint. If the baseline sample does not meet this criterion then no additional CTC samples will be collected after the subject has received 
their first dose of PLX2853. 
15 Urinalysis with urine dipstick is sufficient; if there is significant proteinuria, hematuria, or pyuria, a microscopic examination should be obtained. A complete list of required 
tests is found in Appendix 1 to the protocol. 
16 On PK days, subjects should be instructed not to take their study drug dose (PLX2853, abiraterone acetate, and prednisone or PLX2853 and olaparib) at home. 
17 Additional samples for PK may be collected if a subject experiences a DLT, serious adverse event, AE of special interest, or at the Sponsor’s request. Samples for PK should 
be collected for any dose modification at predose and 0.5, 1, 2, 3, and 5 hours postdose (prior to second daily dose when applicable) 2 weeks (± 1 week) after the modification 
or at the next scheduled clinic visit if occurs no less than 1 week after the modification. The time since the last dose of PLX2853 and abiraterone acetate or PLX2853 and 
olaparib should be noted. 
18 
 
Note:  All PK and PD samples and ECGs should be collected at the specified time points ±10 minutes at the 0.5- and 1-hour sample and ±30 minutes at subsequent time 
points. PK and PD samples should be collected after the corresponding ECGs have been obtained. 
Assessment 
C1D1 
C1D2 
C1D15 
C2+D1 
C2D15 
30-day FU 
ECG  
Predose and at 0.5, 1, 2, 3, and 
5 hours postdose 
Predose 
Predose and at 0.5, 1, 2, 3, and 
5 hours postdose 
Predose and 1 hour postdose 
at the start of each cycle 
Predose and 1 hour 
postdose  
Anytime 
PK for PLX2853, 
abiraterone, and 
olaparib 
Predose and 0.5, 1, 2, 3, and 
5 hours postdose (prior to second 
daily dose when applicable) 
Predose 
Predose and 0.5, 1, 2, 3, and 5 hours 
postdose (prior to second daily dose 
when applicable) 
Predose, 1, and 3 hours 
postdose 
Predose, 1, and 3 hours 
postdose 
Anytime 
PD 
Predose, 3, and 5 hours postdose Predose 
Predose and 3 hours postdose 
Predose 
N/A 
Anytime 

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19 Multiple pharmacodynamics samples and sample types (e.g., serum, whole blood, plasma) may be collected at a given timepoint (detailed sample collection information is 
provided in the Laboratory Manual). 
20 AE monitoring occurs both predose and postdose on days when PLX2853 is taken in the clinic. All AEs will be monitored for approximately 30 days after the last dose of 
study drug or prior to starting any new anti-cancer therapy, whichever occurs first. 
21 CT (or MRI for subjects with a contraindication to contrast) should include at minimum chest, abdomen, and pelvis. Soft tissue progression is assessed per RECIST v1.1 and 
does not require a confirmatory scan. Progression per bone scan is assessed per PCWG3 and requires a confirmatory bone scan at least 6 weeks later. 
22 Radiographic assessment of tumor burden will occur every 9 weeks (±7 days) for the first 24 weeks of treatment (pre-C4, pre-C7, pre-C10), or more frequently as clinically 
indicated. After C10, radiographic assessments will occur every 12 weeks (pre-C14, pre-C18, etc.), or more frequently as clinically indicated. CTCs will be assessed at every 
radiographic assessment as indicated in footnote 14. 
23 PLX2853 and abiraterone acetate should be taken at the same time. PLX2853 and the morning dose of olaparib should be taken at the same time. Subjects should fast for 
2 hours before and 1 hour after taking the PLX2853 and abiraterone acetate or olaparib, except for PK collection days as noted above. The evening dose of olaparib may be 
taken with or without food. The tablets should be swallowed whole with water and not be crushed or chewed. 
24 Prednisone should be taken at least 2 hours before PLX2853 and abiraterone acetate or 1 hour after taking PLX2853 and abiraterone acetate, except for PK collection days 
when subjects should take prednisone 1 hour after taking PLX2853 and abiraterone acetate. 
25 Collection of completed drug diary and distribution of new diary to occur at the beginning of each cycle. 
26 Subjects will be followed until death, withdrawal of consent, or loss to follow-up – every 3 months for the first 2 years and every 6 months thereafter. Survival follow-up can 
be via clinic visit, phone call to the subject or referring physician, or other method deemed appropriate by the site, and should assess survival, progression, subsequent therapy, 
and response. 
27 Any subject with a confirmed response who discontinues treatment for reasons other than disease progression will continue to be followed per standard of care and no less 
than every 3 months until documented disease progression, initiation of a new anti-cancer treatment, or 1 year from discontinuation of study treatment. Response assessment in 
follow up will include at minimum the modality used to determine response (radiographic imaging, PSA, and/or CTC assessment). 
28 If the subject agrees to participate in the optional paired biopsy collection and  the archival tissue provided was collected within 2 months of Screening, a fresh sample does 
not need to be collected at Screening for the optional paired biopsy baseline sample. The paired biopsies should be from the same lesion if possible/feasible, and preferably 
from a non-target lesion. 
29 Abiraterone/Prednisone Only: Subject must be receiving abiraterone acetate 1000 mg QD and prednisone 5–10 mg total daily dose at time of study entry. 
30 Hemoglobin A1c evaluation is required within 28 days of C1D1 for all patients with confirmed or suspected Type 2 diabetes. 
31 Serum testosterone evaluation is required within 28 days of C1D1 and all radiographic response timepoints while on study treatment (every 9 weeks for the first 24 weeks of 
treatment and then every 12 weeks). 
 
 

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SYNOPSIS TABLE 2:  PHASE 2A PLX2853 + ABIRATERONE ACETATE/PREDNISONE OR PLX2853 + OLAPARIB DOSE 
EXPANSION SCHEDULE OF EVENTS 
ASSESSMENTS▼ PROCEDURE▼ 
SCR1 
C1 
C2 
C3 
C4+2 
30-day 
FU3 
LTFU 
 
STUDY DAY► 
-28 to -1 
1 
8 
15 
1 
15 
1 
1 
 
WINDOW (days)► 
 
 
± 2 
± 2 
± 33 
± 3 
± 5 
± 5 
± 7 
± 14 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
History 
Medical history 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Identification of HRR Defect (Olaparib only)4 
X 
 
 
 
 
 
 
 
 
 
Vital 
Vital signs5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Height 
X 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Safety 
Physical exam6 
X 
X7 
X 
X 
X 
X 
X 
X 
X 
 
ECOG 
X 
X7 
X 
X 
X 
X 
X 
X 
X 
 
12-lead ECG8 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
ECHO or MUGA (abiraterone only)9 
X 
 
 
 
 
 
 
 
 
 
Lab 
PG sample 
X 
 
 
 
 
 
 
 
 
 
Hepatitis A, B and C, HIV10 
X1 
 
 
 
 
 
 
 
 
 
Hematology11 
X1 
X7 
X 
X 
X 
X 
X 
X 
X 
 
Chemistry12 
X1 
X7 
X 
X 
X 
X 
X 
X 
X 
 
Coagulation tests13 
X1 
X7 
X 
X 
X 
X 
X 
X 
X 
 
Hemoglobin A1c (Type 2 diabetics only) 
X30 
 
 
 
 
 
 
 
 
 
Testosterone 
X31 
 
 
 
 
 
 
X31 
 
 
PSA 
X1 
X7 
 
 
X 
 
X 
X 
X 
 
Circulating Tumor Cells14 
X 
X7 
 
 
 
 
 
X22 
X 
X27 
Urinalysis15 
X1 
X7 
X 
X 
X 
X 
X 
X 
X 
 
Serum c-reactive protein 
X1 
X 
X 
X 
X 
 
X 
X 
X 
 
PK sample16,17,18 
 
X 
 
X 
X 
X 
X 
X 
X 
 
Biomarker (PD) blood sample19 
 
X 
 
X 
X 
 
X 
X 
X 
 

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ASSESSMENTS▼ PROCEDURE▼ 
SCR1 
C1 
C2 
C3 
C4+2 
30-day 
FU3 
LTFU 
 
STUDY DAY► 
-28 to -1 
1 
8 
15 
1 
15 
1 
1 
 
WINDOW (days)► 
 
 
± 2 
± 2 
± 33 
± 3 
± 5 
± 5 
± 7 
± 14 
Medications, Non-
drug Treatments, 
Radiotherapy 
Prior treatment 
X 
 
 
 
 
 
 
 
 
 
Concomitant Medication Review  
X 
 
AE 
Adverse events20 
X 
 
Treatment Response Archival tissue sample 
X 
 
 
 
 
 
 
 
 
 
Paired biopsy for malignant lesion (optional) 
X28 
 
 
 
X 
 
 
 
 
 
CT Scan21 
X 
 
 
 
 
 
X22 
 
 
X27 
Bone Scan21 
X 
 
 
 
 
 
X22 
 
 
X27 
SSRE evaluation 
X 
 
Treatment 
PLX2853 administration16,23 
 
Daily administration for 21 days (full cycle) 
 
 
Abiraterone acetate or olaparib administration16,23 
X29 
Abiraterone:  QD administration for 21 days (full cycle) or 
Olaparib:  BID administration for 21 days (full cycle) 
 
 
Prednisone administration16,24 
X29 
BID administration for 21 days (full cycle) 
 
 
Study drug compliance (diary review and accountability)25 
 
 
 
 
X 
 
X 
 
X 
 
Survival 
Survival follow-up26 
 
 
 
 
 
 
 
 
 
X 
30-day FU = 30-day follow-up visit; AE = adverse event; aPTT = activated partial thromboplastin time; AUC = area under the concentration-time curve; BID = twice daily; 
C = cycle; CTC = circulating tumor cell; D = day; DLT = dose-limiting toxicity; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group;  
INR = international normalized ratio; LTFU = long-term follow-up visit; PD = pharmacodynamics; PG = pharmacogenomics; PK = pharmacokinetic;  
PSA = prostate-specific antigen; PT = prothrombin time; QD = once daily 
1 
Unless otherwise specified, all screening laboratory tests should be performed within 10 days of C1D1. A complete list of required tests is found in Appendix 1 to the protocol. 
2 
If the subject does not have any ongoing Grade 2 or higher treatment-related AEs and following discussion with the Medical Monitor, subjects on treatment longer than 
12 months may be given the option to only have study visits have study visits every 2 cycles. 
3 
The 30-day FU visit should occur approximately 30 days after the last dose of PLX2853 or prior to starting any new anti-cancer therapy, whichever occurs first. 
4 
Olaparib combination only:  known HRR status assessed per standard of care testing (FoundationOne CDx or BRACAnalysis CDx are suggested). Results of test must be 
available prior to consent. 
5 
Vital signs must be obtained predose (PLX2853, abiraterone acetate, and prednisone) on PK collection days. 
6 
Complete physical examination at Screening and 30-day FU only. All other physical examinations may be abbreviated and symptom-directed. 
7 
ECOG Performance Status, symptom-directed physical examination, hematology, chemistry, coagulation, urinalysis, C-reactive protein, and PSA do not need to be repeated if 
these assessments from Screening occurred within 3 days of C1D1. CTC count does not need to be repeated if the assessment from Screening occurred within 10 days of 
C1D1 unless the screening sample was unable to be processed or a change in status is suspected. Subjects must continue to meet all eligibility criteria that are repeated at the 
time of initiation of C1D1 dosing. 

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8 
All ECGs are single tracings on the specified days and only Screening and predose C1D1 should be done in triplicate (approximately 10 seconds per ECG over a 5-minute 
period). Standard 12-lead ECG with QTcF calculation. Fridericia’s correction is required. QTcF = (QT)/3√(RR). Subjects must continue to meet eligibility criteria on C1D1 
pre-dose assessment in order to proceed with dosing. 
9 
Abiraterone combination only:  ECHO or MUGA will be performed in screening and as clinically indicated once on study. 
10 Serology testing for hepatitis A, B, and C, and HIV should be performed within 28 days of C1D1 if the subject is taking ≤30 µg/day biotin. If the subject is taking >30 µg/day 
biotin, the subject must lower their daily biotin intake to ≤30 µg and wait 14 days before hepatitis A, B, and C serology testing can be performed (elevated levels of biotin may 
interfere with viral serology testing). 
11 Hematology evaluation must include hemoglobin, hematocrit, and white blood cell count with differential and platelet count. A complete list of required tests is found in 
Appendix 1 to the protocol. 
12 Chemistry evaluation must include a complete chemistry panel including liver transaminases, amylase, lipase, and gamma-glutamyl transferase. A complete list of required 
tests is found in Appendix 1 to the protocol. 
13 Coagulation evaluation must include PT/INR, aPTT, fibrinogen, d-dimer, and Factor VII. A complete list of required tests is found in Appendix 1 to the protocol. 
14 Subjects with a positive CTC sample at baseline, as indicated by a value of at least 5 cells/7.5 mL blood, will continue to have CTC samples collected while on treatment at 
each radiographic assessment timepoint. If the baseline sample does not meet this criterion then no additional CTC samples will be collected after the subject has received 
their first dose of PLX2853. 
15 Urinalysis with urine dipstick is sufficient; if there is significant proteinuria, hematuria, or pyuria, a microscopic examination should be obtained. A complete list of required 
tests is found in Appendix 1 to the protocol. 
16 On PK days, subjects should be instructed not to take their study drug dose (PLX2853, abiraterone acetate, and prednisone or PLX2853 and olaparib) at home. 
17 Additional samples for PK may be collected if a subject experiences a DLT, serious adverse event, AE of special interest, or at the Sponsor’s request. Samples for PK should 
be collected for any dose modification at predose and 0.5, 1, 2, 3, and 5 hours postdose (prior to second daily dose when applicable) 2 weeks (± 1 week) after the modification 
or at the next scheduled clinic visit if occurs no less than 1 week after the modification. The time since the last dose of PLX2853 and abiraterone acetate or PLX2853 and 
olaparib should be noted. 
18 
Assessment 
C1D1 
C1D15 
C2-4 D1 
C2D15 
C5+ D1 
30-day FU 
ECG  
Predose 
Predose 
Predose  
Predose  
Predose  
Anytime 
PK for PLX2853, 
abiraterone, and 
olaparib 
Predose and 0.5, 1, 2, 3, and 5 hours 
postdose (prior to second daily dose 
when applicable) 
Predose and 0.5, 1, 2, 3, and 5 hours 
postdose (prior to second daily dose 
when applicable) 
Predose, 1 and 
3 hours postdose 
Predose, 1 and 
3 hours postdose 
Predose 
Anytime 
PD 
Predose, 3 and 5 hours postdose 
Predose, 3 hours postdose 
Predose 
N/A 
Predose 
Anytime 
 
Note:  All PK and PD samples and ECGs should be collected at the specified time points ±10 minutes at the 0.5- and 1-hour sample and ±30 minutes at subsequent time 
points. PK and PD samples should be collected after the corresponding ECGs have been obtained. 
19 Multiple pharmacodynamics samples and sample types (e.g., serum, whole blood, plasma) may be collected at a given timepoint (detailed sample collection information is 
provided in the Laboratory Manual). 
20 AE monitoring occurs both predose and postdose on days when PLX2853 is taken in the clinic. All AEs will be monitored for approximately 30 days after the last dose of 
study drug or prior to starting any new anti-cancer therapy, whichever occurs first. 

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21 CT (or MRI for subjects with a contraindication to contrast) should include at minimum chest, abdomen, and pelvis. Soft tissue progression is assessed per RECIST v1.1 and 
does not require a confirmatory scan. Progression per bone scan is assessed per PCWG3 and requires a confirmatory bone scan at least 6 weeks later. 
22 Radiographic assessment of tumor burden will occur every 9 weeks (±7 days) for the first 24 weeks of treatment (pre-C4, pre-C7, pre-C10), or more frequently as clinically 
indicated. After C10, radiographic assessments will occur every 12 weeks (pre-C14, pre-C18, etc.), or more frequently as clinically indicated. CTCs will be assessed at every 
radiographic assessment as indicated in footnote 14. 
23 PLX2853 and abiraterone acetate should be taken at the same time. PLX2853 and the morning dose of olaparib should be taken at the same time. Subjects should fast for 
2 hours before and 1 hour after taking the PLX2853 and abiraterone acetate or olaparib, except for PK collection days as noted above. The evening dose of olaparib may be 
taken with or without food. The tablets should be swallowed whole with water and not be crushed or chewed. 
24 Prednisone should be taken at least 2 hours before PLX2853 and abiraterone acetate or 1 hour after taking PLX2853 and abiraterone acetate, except for PK collection days 
when subjects should take prednisone 1 hour after taking PLX2853 and abiraterone acetate. 
25 Collection of completed drug diary and distribution of new diary to occur at the beginning of each cycle. 
26 Subjects will be followed until death, withdrawal of consent, or loss to follow-up – every 3 months for the first 2 years and every 6 months thereafter. Survival follow-up can 
be via clinic visit, phone call to the subject or referring physician, or other method deemed appropriate by the site, and should assess survival, progression, subsequent therapy, 
and response. 
27 Any subject with a confirmed response who discontinues treatment for reasons other than disease progression will continue to be followed per standard of care and no less 
than every 3 months until documented disease progression, initiation of a new anti-cancer treatment, or 1 year from discontinuation of study treatment. Response assessment in 
follow up will include at minimum the modality used to determine response (radiographic imaging, PSA, and/or CTC assessment) 
28  If the subject agrees to participate in the optional paired biopsy collection and the archival tissue provided was collected within 2 months of Screening, a fresh sample does not 
need to be collected at Screening for the optional paired biopsy sample. The paired biopsies should be from the same lesion if possible/feasible, and preferably from a 
non-target lesion. 
29 Abiraterone and Prednisone Only: Subject must be receiving abiraterone acetate 1000 mg QD and prednisone 5–10 mg total daily dose at time of study entry. 
30 Hemoglobin A1c evaluation is required within 28 days of C1D1 for all patients with confirmed or suspected Type 2 diabetes. 
31 Serum testosterone evaluation is required within 28 days of C1D1 and all radiographic response timepoints while on study treatment (every 9 weeks for the first 24 weeks of 
treatment and then every 12 weeks). 
 

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1.0 
BACKGROUND AND STUDY RATIONALE 
1.1 
Background 
Cancers are biologically heterogeneous diseases that are characterized by a medley of genomic 
aberrations and mutations. Recently, aberrant regulation of epigenetic processes has emerged as 
a common feature underlying many malignancies, with epigenetic regulation of gene expression 
impacting both the initiation and maintenance of these malignancies. Bromodomain and extra 
terminal domain (BET) proteins in particular serve as a common driver of malignancy through 
their effects on the expression of a specific set of genes essential for tumor growth and survival. 
PLX2853 is an orally active, small molecule inhibitor of BET bromodomain-mediated 
interactions. PLX2853 exhibits low nanomolar potency in blocking all 4 BET family members 
(BRD2, BRD3, BRD4, and BRDT). 
1.2 
Evidence of a Role for BET Proteins in Solid Tumors 
Bromodomains are protein interaction modules that recognize acetylated lysine residues on 
target proteins. Bromodomains are present in diverse nuclear proteins and function as epigenetic 
readers for transcriptional regulators and chromatin modifying enzymes (Filippakopoulos 2012). 
Dysfunction of a subset of bromodomain-containing proteins has been strongly associated with 
the development of cancer (Muller 2011). In particular the BET family bromodomain proteins 
(BRD2, BRD3, BRD4, BRDT) have recently received much attention with the development of 
potent, cell-active inhibitors (Filippakopoulos 2012; Dawson 2011). Pharmacological inhibition 
of BET proteins leads to selective killing of tumor cells across a broad range of malignancies 
(Filippakopoulos 2012; Picaud 2013; Delmore 2011; Zuber 2011; Lockwood 2012; 
Cheng 2013). 
BET proteins facilitate the development of many types of human neoplasms by serving as the 
epigenetic regulators of many genes essential for tumor growth and survival. BET proteins are 
expressed as malignant oncogenic fusions in several rare forms of cancer. In particular, through 
chromosomal translation, BRD4 forms in-frame fusions with the NUT gene to initiate an 
aggressive cancer called NUT midline carcinoma (French 2010). The resulting BRD4NUT 
oncoprotein is an aberrant transcriptional regulator that relies on the bromodomains of BRD4 for 
its oncogenic function (Alekseyenko 2015). Studies using patient-derived NUT midline 
carcinoma xenografts provided the first demonstration of efficacy for a BET inhibitor in a 
preclinical cancer model (Filippakopoulos 2010). BET inhibitors (Filippakopoulos 2010; 
Nicodeme 2010) have since shown therapeutic effects in other solid tumors. For non-small cell 
lung cancer, the effects correlate with suppression of FOSL1 expression (Lockwood 2012; 
Shimamura 2013), while the sensitivity of small cell lung cancer appears to be mediated by 
regulation of ASCL1 gene expression (Lenhart 2015). Neuroblastomas that harbor MYCN 
amplifications are also sensitive to BET inhibition, correlating with suppression of MYCN 
transcription (Puissant 2013; Wyce 2013). In addition, BET inhibitors have also shown antitumor 
activity in genetically diverse glioblastomas (Cheng 2013; Pastori 2015), MYC-amplified 

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medulloblastoma (Bandopadhayay 2014; Henssen 2013), castration-resistant prostate cancer 
(Asangani 2014; Cho 2014), basal-like and Her2-positive breast cancer (Shi 2014; 
Stuhlmiller 2015), and melanoma (Ambrosini 2011; Heinemann 2015). 
1.3 
Role of BET Inhibitors in Metastatic Castration Resistant Prostate Cancer 
1.3.1 
Metastatic Castration Resistant Prostate Cancer 
Prostate cancer is the second leading cause of cancer-related deaths in men in the United States. 
While treatment options are expanding, over 31,000 American men are still predicted to die from 
this disease in 2020 (Siegel 2019). The principal treatments for advanced prostate cancer are 
based on disrupting androgen receptor (AR) function, either by blocking production of 
androgens or by inhibiting androgen binding to its receptor. However, resistance to these 
treatments and disease progression is nearly universal. Patients who develop metastatic 
castration-resistant prostate cancer (mCRPC) generally succumb to the disease. Progression to 
mCRPC after androgen deprivation therapy (ADT) is driven by deregulated AR signaling 
(Taylor 2010; Chen 2004; Visakorpi 1995). Maintenance of AR signaling is the most common 
resistance mechanism that develops after conventional hormone treatments (Harris 2009). 
AR amplification, mutation or alternative splicing have all been identified as resistance 
mechanisms to anti-androgen treatments (Chen 2004; Taplin 1999; Sun 2010). Over one half of 
mCRPC patients have at least one of these aberrations in the AR pathway (Grasso 2012). 
Therapies that target AR signaling including abiraterone + prednisone (Stein 2012; Reid 2010; 
de Bono 2011) and enzalutamide (Mukherji 2012; Scher 2012) have become first-line therapies 
for mCRPC. Additionally, the PARP inhibitor, olaparib, has recently been approved for patients 
with HRR after progression on abiraterone or enzalutamide. As these are oral agents and 
generally well tolerated, they are favored over chemotherapy. Despite the success of AR 
signaling inhibitors and PARP inhibitors, durable responses are limited. All mCRPC patients will 
eventually progress despite evidence-based first-line treatments that patients receive. Additional 
agents with complementary mechanisms of action are required to help improve clinical 
outcomes. 
1.3.2 
Combination of BET Inhibitors with AR Signaling Inhibitors 
Recent preclinical studies have shown that AR-signaling-competent human CRPC cell lines are 
preferentially sensitive to BET inhibitors (Asangani 2014). BRD4 physically interacts with the 
N-terminal domain of AR and can be disrupted by BET inhibitors such as JQ1 (Delmore 2011; 
Filippakopoulos 2010). Inhibiting the AR-BRD4 interaction disrupts transcription of AR target 
genes (Asangani 2014) and represents a promising strategy to block the function of AR in 
mCRPC resistance. BET inhibition by PLX2853 was found to be efficacious in CRPC xenograft 
mouse models such as VCaP model. This model is comprised of cells expressing both WT AR as 
well as the truncated variant ARv7 which can drive expression of AR target genes in the absence 
of androgen. Since BET inhibitors like PLX2853 can disrupt pathways downstream of AR by 
inhibiting multiple acetyl-lysine interactions, we have shown that PLX2853 in combination with 
abiraterone (EXP-20-AG9412) and enzalutamide (EXP-20-AH3303) can potentiate the 

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anti-androgenic effect as well as potentially overcome resistance to anti-androgenic therapies. 
This study will evaluate whether PLX2853 in combination with abiraterone + prednisone 
represents an effective approach for overcoming resistance to the approved therapy. Abiraterone 
+ prednisone is selected based on the interim results from an ongoing randomized phase II study 
that favors abiraterone + prednisone over enzalutamide in patients with treatment-naïve mCRPC 
(Khalaf 2018). 
1.3.3 
Combination of BET Inhibitors with PARP Inhibitors 
There is a unique subset of mCRPC patients with tumors harboring deleterious mutations in 
DNA-repair genes, in particular genes involved in homologous recombination repair (HRR). In 
these patients poly(ADP-ribose) polymerase (PARP) inhibitors have been reported to confer high 
rates of response. Recently, FDA has approved olaparib for the treatment of adult patients with 
deleterious or suspected deleterious germline or somatic homologous recombination repair 
(HRR) gene-mutated mCRPC who have progressed following prior treatment with enzalutamide 
or abiraterone acetate +prednisone. This represents an example of how mCRPC treatment can be 
tailored according to the tumor mutation profile. BET inhibitors have been shown to induce 
homologous recombination defects (HRD). This supports the evaluation of PLX2853 in 
combination with olaparib in mCRPC, 
1.4 
PLX2853 
Unlike the first generation BET inhibitors including JQ1 (Filippakopoulos 2010), I-BET762 
(Mirguet 2013), and OTX015 (Boi 2015), PLX2853 is structurally unrelated to the 
benzodiazepines. The nonclinical pharmacology, pharmacokinetics (PK), and toxicology profiles 
of PLX2853 have been characterized in an extensive program of in vitro and in vivo studies. The 
data from these studies supported clinical development of PLX2853 as a novel epigenetic 
therapy for certain solid tumor cancers. PLX2853 is currently in clinical development for both 
hematologic malignancies (Study PLX124-02 [NCT03787498]) and solid tumors 
(Studies PLX124-01 [NCT03297424] and PLX124-03 [NCT04493619]). The data to date have 
demonstrated evidence of antitumor activity with manageable toxicity. In clinical experience 
with PLX2853 monotherapy, at the time of protocol initiation, 2 evaluable subjects with heavily 
pretreated mCRPC were enrolled into a PLX2853 dose escalation study (PLX124-01; 
NCT03297424) with one subject having stable disease after 2 cycles of treatment before 
progressing after 4 cycles of treatment. 
1.4.1 
Nonclinical Pharmacology 
The 4 BET family proteins, BRD2, BRD3, BRD4 and BRDT, share the feature of containing 
2 conserved N-terminal bromodomains (BD1 and BD2), an extra terminal domain, and a 
divergent C-terminal recruitment domain. The dissociation constant (Kd) values of PLX2853 
were determined for the 8 isolated BET bromodomains. Based on the measured Kd values, 
PLX2853 is more potent against isolated bromodomains from the BET proteins BRD2, BRD3, 
and BRD4 than those from the testes-specific BRDT (Table 1). Within these isolated domains 

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there is a slight preference for binding to the BD2. Structural analyses of the interactions of BET 
proteins with histone tails suggested that both BD1 and BD2 are involved in the recognition of 
acetyl-lysine epitopes. Thus, potent inhibition of both bromodomains likely contributes to the 
overall pharmacological effects of PLX2853. In biochemical assays that examined the binding of 
acetylated histone tail to BET proteins containing both bromodomains, PLX2853 displayed 
potent inhibitory activity (inhibitory concentration [IC]50 = 4.3 nM for BRD4 and 7.3 nM for 
BRD2) (EXP-16-AE6869). 
Table 1: 
Kd Values of PLX2853 for Binding to the 8 Bromodomains from 4 BET 
Proteins 
Bromodomaina 
PLX2853 Kd (nM) 
BRD2 (BD1) 
0.32 
BRD2 (BD2) 
0.21 
BRD3 (BD1) 
0.34 
BRD3 (BD2) 
0.21 
BRD4 (BD1) 
0.51 
BRD4 (BD2) 
0.24 
BRDT (BD1) 
1.5 
BRDT (BD2) 
3.9 
Source:  EXP-15-AD5580 
a 
Each assay used a truncated protein containing a single bromodomain. The 2 bromodomains of each BET 
protein are labeled as BD1 and BD2, respectively. 
 
Binding interactions of PLX2853 to 24 isolated bromodomains from 22 different proteins were 
measured using BROMOscan (EXP-15-AD5580). At a 1 μM concentration, PLX2853 shows 
interactions with the bromodomains in 3 non-BET proteins, CREBBP, EP300, and TAF1-BD2. 
The Kd values of PLX2853 were determined for all bromodomains that showed >50% binding in 
the single concentration primary screen. Of the non-BET proteins, only CREBBP and EP300 had 
sub-micromolar potencies with Kd values in the 100 nM range. 
A functional MYC reporter assay was generated by placing a firefly luciferase gene construct 
under the control of a minimal CMV promoter and tandem repeats of a MYC binding element 
(E-box) to determine the cellular pharmacodynamic effect of PLX2853. PLX2853 potently 
inhibits MYC reporter activity in MV4-11 cells with an IC50 of 7.2 nM (EXP-16-AE6870). 
The antitumor effects of PLX2853 were also evaluated in a panel of 127 solid tumor cell lines 
(EXP-15-AD8492), including five corresponding to prostate cancer cell lines (Table 2). Prostate 
cancer cell lines show sensitivity to PLX2853. This finding provides a rationale for testing 
PLX2853 as a potential new therapy in the treatment of prostate cancer. 

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Table 2: 
IC50 Values for PLX2853, Enzalutamide, and Niraparib in Prostate Cancer 
Cell Growth Assays 
Cell Line 
AR Status 
BRCA 
Status 
PLX2853  
IC50 (µM) 
[CI95 (µM)] 
Enzalutamidea 
IC50 (µM) 
[CI95 (µM)] 
Niraparibb  
IC50 (µM) 
[CI95 (µM)] 
DU145  
AR negative 
BRCA1/2 
mutation 
0.73 
[0.596–0.895] 
7.88 
[N/A] 
13.3 
[12.6–14.1] 
PC3 
AR negative 
  
0.655 
[N/A] 
>30 
[N/A] 
2.3 
[N/A] 
LNCaP 
AR positive 
BRCA2 
mutation 
0.00885 
[0.00801–0.00978] 
5.26 
[3.4–8.14] 
3.73 
[3.22–4.32] 
22Rv1  
AR positive, 
full length and 
ARv7 
BRCA2 
mutation 
0.0203 
[0.0179–0.0229] 
>30 
[N/A] 
2.56 
[2.16–3.03] 
VCaP  
AR positive 
  
0.00348 
[0.00314–0.00385] 
2.57 
[1.23–5.4] 
7.59 
[5.8–10] 
Source:  EXP-20-AH3303 
CI95 = 95% confidence interval; IC50 = Half maximal inhibitory concentration 
a 
Enzalutamide was used as representative AR signaling inhibitor. 
b 
Niraparib was used as representative PARP inhibitor. 
 
Progression to mCRPC after ADT is primarily due to deregulated AR signaling. Initial 
treatments with agents such as abiraterone acetate and enzalutamide are successful but acquired 
resistance develops frequently. A number of paths leading to primary and acquired resistance to 
anti-androgen therapies have been reported. These include overexpression of androgen synthesis 
enzymes, amplification, and point mutations in AR, overexpression of the AR splice variant 
(ARv7), and induction of GR. BET inhibitors have been shown to avert these resistance 
mechanisms in vivo with mechanisms of action supported by extensive in vitro analyses 
(Vázquez 2019). In the xenograft model with 22Rv1 cell line, PLX2853 resensitizes both 
abiraterone and enzalutamide (Figure 1). We anticipate that combining PLX2853 with anti-
androgen agents such as abiraterone acetate + prednisone and enzalutamide will result in more 
durable therapeutic responses in clinic. 

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Figure 1: 
PLX2853 in Combination with Abiraterone and Enzalutamide in the 
22Rv1 Xenograft Model 
 
Source:  EXP-20-AG9412 
 
BET inhibitors including PLX2853 have also been shown to induce homologous recombination 
defects (HRD) in cells which can render them sensitive to PARP inhibition. BET inhibitors and 
PARP inhibitors have shown strong synergy in tumor cells with germline or somatic mutations 
conferring a HRD state, resulting in improved efficacy in both in vitro and in vivo studies 
(Asangani 2014; Vázquez 2019). The ability of BET inhibitors to overcome resistance to PARP 
inhibition derives from their ability to induce HRD through down regulation of DNA-repair and 
damage response genes as well as other epigenetic modifications brought about by BET 
inhibition. 
Together these data support two approaches:  1) the combination of PLX2853 with abiraterone 
acetate as a concerted blockade of AR signaling, the oncogenic driver in advanced CRPC; 2) 
potential for enhanced efficacy when combining PLX2853 with a non-AR-targeted therapy such 
as a PARP inhibitor (olaparib). Both strategies provide new possibilities to improve clinical 
outcomes for patients with advanced mCRPC. 
Recently, immunotherapies and especially checkpoint inhibitors have shown significant clinical 
benefit in selected patient populations. These therapies can offer broader clinical benefit with 
0
200
400
600
800
1000
1200
1400
1600
1800
0
7
14
21
28
35
Tumor Volume (mm³)
Study Days
Vehicle
PLX2853
Abiraterone (ABI)
enazlutamide (ENZ)
PLX2853 + ABI
PLX2853 + ENZ

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auxiliary strategies to mitigate the immunosuppressive nature of the tumor microenvironment. A 
selective BET inhibitor holds promise to improve the efficacy of cancer immunotherapies. By 
inhibiting the accumulation of immunosuppressive macrophages and myeloid-derived suppressor 
cells, BET inhibitors have been shown to reprogram the tumor microenvironment to facilitate 
T cell-mediated antitumor immunity (Zhu 2016). Study EXP-16-AF3502 evaluated the potential 
of combining PLX2853 with αCTLA4 in the treatment of solid tumors using the MC38 
syngeneic xenograft model. As single agent, PLX2853 at 6 mg/kg once daily (QD) and αCTLA4 
performed equally well, resulting in 78% and 74% tumor growth inhibition (TGI), respectively, 
by the end of a 21-day dosing period. The combined treatment generated stronger efficacy, 
achieving nearly complete (93%) TGI. A similar TGI (95%) and a higher rate of complete 
response (CR) were observed when a higher dose of PLX2853 administered every other day was 
combined with αCTLA4. The 5 animals in this group that had achieved sustained CRs rejected 
the re-implantation of MC38 tumor cells, illustrating the development of full immunity in these 
animals (Zhu 2016). 
1.4.2 
Nonclinical Pharmacokinetics 
PLX2853 is an achiral molecule with a molecular weight of 515.6 Da. The absorption, 
distribution, metabolism, and elimination properties of PLX2853 have been characterized 
through a comprehensive panel of nonclinical in vitro and in vivo studies. PLX2853 is lipophilic 
with a logP of 4.15 and a logD (pH 7.4) of 0.93. Because the molecule contains ionizable groups, 
the aqueous solubility of PLX2853 is pH-dependent. PLX2853 is more soluble at both low and 
alkaline pH. The presence of bio-relevant media (e.g., simulated intestinal or gastric fluid) 
appears to have minor impact on its aqueous solubility. PLX2853 has a solubility of 94.3 µM 
(48.6 µg/mL) at pH 7 and is stable in simulated intestinal and gastric fluids. PLX2853 shows 
high bidirectional permeability across Caco-2 monolayers with a low efflux ratio. Because of its 
moderate solubility and high permeability, PLX2853 is a Biopharmaceutics Classification 
System class II drug with oral absorption limited by the dissolution rate. 
The preclinical PK of PLX2853 was evaluated in 3 species (mouse, rat, and dog) following 
intravenous (IV) and oral administration of the compound. PLX2853 exhibited low IV clearance 
(CL) in all 3 species (CL = 1.68, 2.71, and 2.69 mL/min/kg in mice, rats, and dogs, respectively) 
with a terminal elimination half-life (T1/2) of 2 hours or less. Rat and dog, the 2 species selected 
for preclinical safety testing, were used more extensively to evaluate the PK and bioavailability 
of oral doses of PLX2853. Because of the limited solubility, an immediate-release amorphous 
formulation using spray-dried dispersion technology was developed to enhance bioavailability of 
PLX2853. In both single-dose and repeat-dose PK studies, the time required to reach maximum 
observed concentration (Tmax) was usually within 2 hours following oral administration. In the 
definitive 28-day Good Laboratory Practice (GLP) rat and dog toxicology studies, PLX2853 
showed near dose-proportional increase in exposure over the dose range evaluated. Because of 
the relatively short T1/2, only a modest level of accumulation was observed at steady state. At the 
highest dose, the exposure, in terms of AUC0-24, was slightly lower in females than in males, 
though differences were less than 2-fold. 

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In the IND-enabling toxicology studies, PLX2853 was quantified in plasma using fully-validated 
liquid chromatography tandem mass spectrometry (LC/MS/MS) bioanalytical methods. Two 
GLP-compliant studies validated chromatographic methods used for quantification of PLX2853 
in rat and dog plasma samples, as well as in aqueous media. The first method was performed 
using high performance liquid chromatography (HPLC) coupled with electro spray ionization in 
positive ion mode (ESI+) (LC/MS/MS) for rat and dog plasma sample analysis, and the second 
method was performed with HPLC coupled with ultraviolet (UV) absorption for dosing solution 
analysis. 
Protein binding of PLX2853 is moderate to high in human (96.1%), monkey (93.4%), dog 
(95.5%), rat (97.9%), and mouse (95.4%) plasma. PLX2853 is stable in the plasma of all 
5 species. In a single-dose tissue distribution study in rats, the brain penetration of PLX2853 was 
minimal with a brain to plasma ratio of <0.01 two hours after administration of 10 mg/kg oral 
dose of PLX2853. 
PLX2853 is metabolically stable. The metabolic turnover was low for PLX2853 in mouse, rat, 
dog, monkey, and human S9 fractions (S9-based intrinsic clearance <4.9 µL/min/mg in all 
5 species). Liver S9 metabolite profiling identified an oxidation metabolite (labeled M1) in 
human and dog and no major metabolites in rat. Cytochrome P450 (CYP) reaction phenotyping 
indicates that CYP2C8 and CYP3A4 are the major contributors for the formation of the 
PLX2853 oxidative metabolite M1. Their relative contributions to the formation of M1 were 
similar. However, because the rate of oxidative metabolism is so low, CYP2C8 and CYP3A4 
inhibitors are not expected to have a significant effect on the clearance of PLX2853. 
The excretion profiles of PLX2853 in bile duct-cannulated (BDC) male Sprague Dawley rats 
following IV administration were determined. Following IV administration of 1, 10, and 
25 mg/kg PLX2853 to BDC rats, by 24 hours postdose, 4.08, 5.56, and 4.56% and 0.118, 0.082, 
and 0.587% of the administered dose were recovered as PLX2853 in bile and urine, respectively. 
Based on these data, biliary and urinary excretion of untransformed PLX2853 do not appear to 
be major routes of elimination of PLX2853 in rats. 
The drug-drug interaction potential of PLX2853 was further evaluated by measurement of CYP 
inhibition using recombinant enzymes and CYP induction potential in human hepatocytes. 
Studies have also been conducted to assess the potential of PLX2853 as an inhibitor of human 
breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), organic anion transporter 
(OAT)1, OAT3,organic cation transporter (OCT)2, organic anion transporting polypeptide 
(OATP)1B1, and OATP1B3 mediated transport in polarized monolayer of MDCK-II cells. 
PLX2853 demonstrated no potential to cause reversible and/or time-dependent inhibition of 
CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4. PLX2853 did not induce  CYP1A, CYP2B, and 
CYP3A genes at all the concentrations tested in human, monkey, dog, and rat hepatocytes, 
except CYP3A in monkey (34% to 49% of the positive control). Compared to vehicle control, 
PLX2853 at 10 µM inhibited OCT2, OATP1B1, OATP1B3, BCRP, and P-gp mediated transport 
by 24.4%, 82.4%, 50.7%, 37.2%, and 48.8%, respectively. Considering the plasma protein 
binding of PLX2853 (96.1% in human), the plasma concentration to achieve 10 µM free fraction 

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is >250 µM, well beyond the anticipated in vivo exposures. Collectively, these results suggest 
that the risk of in vivo drug-drug interactions is low for PLX2853. 
The food effect on the PK of PLX2853 was evaluated following a single oral dose to male beagle 
dogs under fasted or fed (high fat diet) conditions. This was a single-dose, 2-period crossover 
study where each group received a 40 mg dose of PLX2853 (two 20 mg strength tablets) while 
either fasted or fed and then received the alternate treatment (fasted or fed) following a washout 
period of 4 days (96 hours) between doses. Dogs receiving the high fat diet resulted in a 
significant reduction in exposure of PLX2853. The mean Cmax values were 903 and 4870 ng/mL 
for fed and fasted groups, respectively. The mean AUC0-24 values were 3280 and 
14,100 ng•hr/mL for fed vs fasted groups, respectively. The geometric mean ratios (fed/fasted) 
with the calculated CI90 for the ratios for Cmax, and AUC0-24, and area under the concentration-
time curve from time zero extrapolated to infinite time (AUC0-∞) were 17.72% (11.71% to 
26.81%), and 25.15% (18.34% to 34.548%), and 25.82% (18.92% to 35.24%), respectively. 
1.4.3 
Toxicology Studies of PLX2853 
The PLX2853 toxicology program is consistent with the guidance provided in the International 
Council for Harmonisation (ICH) S9 guideline and is comprised of repeat-dose exploratory 
toxicology studies and definitive 4-week toxicology studies conducted in 2 mammalian species 
(rat and dog) using the clinically-relevant route of administration (oral) and dosing schedule 
(continuous daily administration). Additionally, definitive in vitro and in vivo genotoxicity 
studies were conducted. Clinically-relevant polymer-based blend formulations of PLX2853 were 
used in the dose-range finding and definitive in vivo studies. Doses/concentrations of test article 
used in the definitive studies were corrected for polymer loading and reflect the 
dose/concentration of active moiety. PLX2853 was administered to rats via oral gavage and to 
dogs via oral capsule. An overview of the PLX2853 toxicology program is provided in Table 3. 

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Table 3: 
Overview of PLX2853 Toxicology Program 
Study Type  
(Study Number)  
Species 
and Strain 
Method of 
Administration 
Doses (mg/kg/day)a 
Repeat-dose Toxicity 
 
 
 
14-day dose range-finding 
(EXP-15-AC2093) 
Rat/Crl:CD 
(Sprague Dawley) 
Oral (gavage) 
0, 1b, 5, 10 
28-day definitive 
(EXP-16-AF1301) 
Rat/Crl:CD 
(Sprague Dawley) 
Oral (gavage) 
0, 0.5, 1.5, 5c 
14-day dose range-finding 
(EXP-16-AC2095) 
Dog/Beagle 
Oral (capsule) 
0, 1, 3, 6 
28-day definitive 
(EXP-16-AF1302) 
Dog/Beagle 
Oral (capsule) 
0, 0.3, 1c, 3 
Genotoxicity 
 
 
 
Bacterial reverse mutation 
assay 
(EXP-16-AF1308) 
S. typhimurium, E. coli  
In vitro  
≤5000 μg/plate 
Chromosome aberration 
assay 
(EXP-16-AF1309) 
Human (peripheral blood 
lymphocytes) 
In vitro 
3 hours without metabolic 
activation:  3.13–250 µg/mL 
3 hours with metabolic  
activation:  0.783–3.13 µg/mL 
22 hours without metabolic 
activation:  0.0061–0.0244 µg/mL  
Erythrocyte micronucleus 
assay and alkaline comet 
assay 
(EXP-20-AF1337) 
Rat/Crl:CD 
(Sprague Dawley) 
Oral (gavage) 
5, 10, 20, 40 
Other Toxicity Studies 
 
 
 
Phototoxicity assay 
(EXP-16-AF0914) 
NIH/3T3  
(ATCC® CRL-1658™) 
In vitro 
≤50 µM 
Hepatocyte cytotoxicity assay 
(EXP-16-AF0943) 
Human 
In vitro 
0.07–50.00 µM 
Cell viability assay 
(EXP-16-AF0957) 
Human kidney (293T) 
and liver (HepG2) cell 
lines 
In vitro 
≤50 µM 
HNSTD = highest non-severely toxic dose; NOAEL = no-observed-adverse-effect-level 
a 
Unless otherwise specified. For repeat-dose toxicity, the NOAEL is underlined. 
b 
NOAEL for females; the NOAEL for males could not be defined. 
c 
HNSTD for both males and females. A NOAEL could not be determined for either sex. 
 
The rat and dog were selected for the PLX2853 toxicology program as the rodent and nonrodent 
toxicology species, respectively, on the basis of in vitro metabolism studies which indicated that 
metabolism of PLX2853 in rat and dog hepatocytes is qualitatively comparable to that in human 
hepatocytes. 
In both rats and dogs, 14-day exploratory studies were conducted as dose range-finders for 
subsequent 28-day definitive studies. In rats, QD oral administration of PLX2853 at dose levels 

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of 1, 5, and 10 mg/kg/day for up to 14 consecutive days resulted in moribundity at 10 mg/kg/day 
in both sexes, resulting in early termination of 10 mg/kg/day animals on Day 7. Adverse test 
article-related microscopic findings noted in PLX2853-treated rats included:  increased minimal 
to moderate thickness of the femoral physis in males at all dose levels; atrophy and lymphoid 
depletion in the thymus and lymphoid depletion in the spleen in both sexes at 5 mg/kg/day; and 
minimal atretic follicles in the ovary, and an alteration in estrous cyclicity in females at 5 and 
10 mg/kg/day. Under the conditions of this study, the highest non-severely toxic dose (HNSTD) 
of PLX2853 was considered to be 5 mg/kg/day for both sexes. Systemic exposure (AUC0-24 and 
Cmax) at the HNSTD on Day 13 was 9420 ng•hr/mL and 1580 ng/mL, respectively for males and 
2350 ng•hr/mL and 771 ng/mL, respectively, for females. The no-observed-adverse-effect level 
(NOAEL) for PLX2853 in this study was considered to be 1 mg/kg/day for females but could not 
be defined for males. Based on the results of this dose range-finding study, PLX2853 dose levels 
of 0.5, 1.5, and 5 mg/kg/day were selected for evaluation in the subsequent 28-day definitive 
toxicity study. In the 28-day study, QD oral administration of PLX2853 for a minimum of 
28 consecutive days resulted in adverse test article-related effects including reduced body weight 
gain and food consumption in males at 1.5 and 5 mg/kg/day. Adverse microscopic findings in 
lymphoid and hematopoietic tissues at the terminal necropsy included:  hypocellularity of the 
bone marrow at 0.5 (females only), 1.5, and 5 mg/kg/day in both sexes, with clinical pathology 
correlates of decreased mean total white blood cell, absolute lymphocyte, and basophil counts at 
all dose levels, decreased mean absolute eosinophil counts (males only) at 5 mg/kg/day, and 
possibly decreased mean platelet count (males only) at 5 mg/kg/day; atrophy of the thymus in 
males at all dose levels and atrophy and lymphoid necrosis of the thymus in females at 
5 mg/kg/day; and lymphoid depletion of the spleen, mesenteric lymph node (males only), and/or 
thymus in males at all dose levels and in females at 1.5 and 5 mg/kg/day (correlating in males 
with decreased mean absolute lymphocyte counts, decreased mean thymus and spleen weights at 
all dose levels, and macroscopic small thymus at 5 mg/kg/day and in females with decreased 
mean thymus and spleen weights at 1.5 and 5 mg/kg/day). All adverse effects were resolved 
following the 28-day treatment-free recovery period. Under the conditions of this study, the 
HNSTD for PLX2853 was considered to be 5 mg/kg/day. Systemic exposure (AUC0-24 and Cmax) 
at the HNSTD on Day 27 was 1800 ng•hr/mL and 1400 ng/mL, respectively for males and 
1190 ng•hr/mL and 1370 ng/mL, respectively, for females. A NOAEL could not be determined 
for either sex in this study. 
In dogs, QD oral administration of PLX2853 at dose levels of 1, 3, and 6 mg/kg/day for up to 
14 consecutive days resulted in overt toxicity in both sexes at the 6 mg/kg/day high-dose level. 
Two of 3 high-dose male animals were euthanized in moribund condition on Days 5 and 12. As a 
result, the surviving high-dose animals were scheduled for early termination on Day 13. Adverse 
test article-related findings in PLX2853-treated dogs included:  intestinal mucosal changes, 
lymphoid depletion, necrosis of lymphoid organs, bone marrow hypocellularity, and 
prolongations of activated partial thromboplastin time (aPTT) in both sexes; atrophy of the 
thymus, correlating with macroscopic findings and effects on thymic weight in both sexes at 
3 mg/kg/day; and lesions in the male reproductive tract at 3 mg/kg/day. Under the conditions of 
this study, the HNSTD for PLX2853 was considered to be 3 mg/kg/day for both sexes, while the 

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NOAEL was considered to be 1 mg/kg/day for both sexes. Systemic exposure (AUC0-24 and 
Cmax) at the HNSTD on Day 13 was 5050 ng•hr/mL and 1900 ng/mL, respectively for males and 
879 ng•hr/mL and 203 ng/mL, respectively, for females. Systemic exposure (AUC0-24 and Cmax) 
at the NOAEL on Day 13 was 2600 ng•hr/mL and 503 ng/mL, respectively for males and 
1230 ng•hr/mL and 333 ng/mL, respectively, for females. Based on the results of this dose 
range-finding study, PLX2853 dose levels of 0.3, 1, and 3 mg/kg/day were selected for 
evaluation in the subsequent 28-day definitive toxicity study. In the 28-day study, all animals 
administered 0.3 or 1 mg/kg/day PLX2853 survived until scheduled termination, whereas 
animals administered 3 mg/kg/day PLX2853 were submitted for early termination on the day of 
the scheduled terminal necropsy. Once daily administration of 3 mg/kg/day PLX2853 resulted in 
adverse clinical observations indicating severe toxicity, body weight loss, reduced food 
consumption, altered organ weights, altered hematology, coagulation, and clinical chemistry 
parameters, and macroscopic and microscopic findings in both males and females. Test 
article-related effects included:  erosion/ulcer and/or hemorrhage in the gastrointestinal tract 
tissues and lung hemorrhage and inflammation, together with concurrent altered serum 
electrolytes, prolonged prothrombin time, and aPTT, and decreased platelet and reticulocyte 
counts at 3 mg/kg/day; tubular degeneration in the testes with associated epididymides and 
prostate changes at 1 and 3 mg/kg/day; hypocellular marrow in both sexes at all dose levels; and 
thymic atrophy, lymphoid depletion of Peyer’s patches and axillary lymph nodes in both sexes at 
3 mg/kg/day. In addition, 1 male in the 0.3 mg/kg/day low-dose group was noted for hemorrhage 
and inflammation in the lung, which was considered adverse. Following 28 days of 
treatment-free recovery, microscopic findings had either completely resolved or were considered 
to be in the process of resolving. Under the conditions of this study, the HNSTD for PLX2853 
was considered to be 1.0 mg/kg/day in both sexes. Systemic exposure (AUC0-24 and Cmax) at the 
HNSTD on Day 27 was 1940 ng•hr/mL and 935 ng/mL, respectively for males and 
1610 ng•hr/mL and 775 ng/mL, respectively, for females. A NOAEL could not be determined 
for either sex in this study. 
PLX2853 was found to be non-mutagenic in a definitive bacterial reverse mutation assay. In a 
definitive in vitro chromosome aberration assay conducted in human peripheral blood 
lymphocytes, PLX2853 was considered positive for inducing structural aberrations in the 3-hour 
treatment without metabolic activation. In addition, statistically significant increases in 
numerical aberrations (polyploidy or endoreduplication) were noted PLX2853-treated cultures 
after 3 hours of treatment without metabolic activation. PLX2853 was also evaluated for its 
genotoxic potential in vivo in the bone marrow and liver of rats. In the micronucleus assay, 
increases in the incidence of micronucleated polychromatic erythrocytes (MnPCEs) were 
observed at ≥10 mg/kg. In the comet assay, no increases in % tail DNA were observed. 
Therefore, PLX2853 was positive for the induction of MnPCEs in rat bone marrow and negative 
for the induction of DNA damage in liver. The in vivo rat micronucleus assays results are 
consistent with the in vitro chromosomal aberration and indicate a potential for genotoxicity. 

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In a preliminary assessment of photosafety, PLX2853 did not reduce the viability of 3T3 mouse 
fibroblasts with and without UV A exposure and was therefore concluded to have no phototoxic 
potential. 
In exploratory in vitro studies, PLX2853 was not toxic to human hepatocytes in culture after 
either 24 or 72 hours of exposure (IC50 >50 μM) and did not reduce the viability of human 
HepG2 or 293T cells after either 24 or 72 hours with 10% fetal bovine serum (IC50 >50 μM), 
indicating that the metabolites of PLX2853 are not toxic to liver and kidney cells. 
Additional detailed information regarding the nonclinical pharmacology and toxicology of 
PLX2853 can be found in the Investigator’s Brochure. 
1.4.4 
Proposed Starting Dose for Study PLX124-04 
The RP2D of 80 mg QD was determined in consideration of the totality of clinical, PD, and PK 
data across both advanced solid tumors and hematological malignancies. No DLTs were 
observed at or below 80 mg QD in Study PLX124-01 and Study PLX124-02 and in the safety 
lead-in of Study PLX124-03. An appropriate therapeutic index was observed at the RP2D with a 
sustained PD effect, and clinical efficacy was achieved across a broad range of malignancies at 
or below the RP2D. 
Combination treatment with PLX2853 + abiraterone acetate + prednisone or PLX2853 + 
olaparib may have a different safety profile compared with PLX2853 single agent. To ensure 
adequate safety margin in the combination trial, a starting dose of 40 mg/day for PLX2853 is 
recommended. Based on the clinical PD results and preclinical experience, the proposed starting 
dose of 40 mg/day for PLX2853 with abiraterone acetate + prednisone or with olaparib 
combination therapy is expected to be pharmacologically active and reasonably safe. 
1.5 
Study Rationale 
During the past 15 years, there has been significant scientific progress and investment in drug 
development for patients with mCRPC. This has resulted in the market approval of several lines 
of systemic therapies on grounds of pain palliation, minimizing disease adverse effects, and 
overall survival (OS) prolongation. However, the reported impact on OS in mCRPC patients 
from each of these individual agents is still modest, resulting in an addition of only a few 
months. It is necessary to explore new molecular understanding of castration resistance and 
complementary mechanisms of action to enhance current therapies and improve clinical 
outcomes. 
BET inhibitors such as PLX2853 have shown efficacy preclinically in multiple tumor types, 
including CRPC (Asangani 2014; Faivre 2018; Welti 2018; Pawar 2019; Coleman 2019). The 
transcription factor drivers of CRPC progression, including AR, are critically dependent on BET 
family members such as BRD4. In particular, BET inhibition disrupted the composition and 
function of AR-occupied enhancers. BET inhibitors inhibited the activity of the AR splice 

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variant ARdv7 and ligand-binding domain gain-of-function mutations, F877L and L702H. BET 
inhibitors also inhibit the activities of important parallel transcription factor drivers of CRPC 
such as MYC. In vivo, BET inhibitors displayed potent antiproliferative activity in models of 
resistance to second generation antiandrogens represented by abiraterone and enzalutamide 
(EXP-20-AH3303). 
BET inhibitors including PLX2853 have also been shown to induce homologous recombination 
(HR) defects in cells which can render them sensitive to PARP inhibition. PARP inhibition is a 
recently approved approach for targeting and treating tumors with deficiencies in DNA repair 
mechanisms. The PARP family of enzymes are required for the correct repair of DNA single 
strand breaks. Inhibition of PARP enzymes leads to an increase in DNA single strand breaks 
which then lead to increased double strand breaks during replication. Cells that have functional 
homologous recombination (HR) machinery can correct these double strand breaks during cell 
division. However, cells that contain defects in their HR machinery are incapable of repairing 
such breaks and will undergo apoptosis. PARP inhibitors olaparib and rucaparib have recently 
been approved for the treatment of mCRPC patients with suspected or deleterious germline or 
somatic mutations associated with homologous recombination repair (HRR) genes who have 
progressed on prior treatment with abiraterone acetate or enzalutamide. Hence, there is a 
rationale for the combination of PLX2853 and olaparib in the treatment of prostate cancer based 
on their complementary mechanisms of action. 
This study will evaluate the investigational drug PLX2853 when given on a background of the 
approved drug abiraterone acetate + prednisone in patients with mCRPC. PLX2853 will also be 
evaluated when given on a background of the approved drug olaparib in mCRPC patients with 
germline or somatic mutations in HRR genes identified by FoundationOne CDx or 
BRACAnalysis CDx. These two parallel groups will provide an initial assessment of 
safety/tolerability and potential for pharmacokinetic (PK) interaction between the respective 
drugs. In the PLX2853-abiraterone acetate + prednisone combination, subjects with mCRPC 
who develop disease progression whilst currently receiving initial treatment with abiraterone 
acetate + prednisone will be studied. Subjects with deleterious or suspected deleterious germline 
or somatic HRR genes mutated mCRPC who have progressed following prior treatment with 
abiraterone acetate + prednisone or enzalutamide will be studied in the PLX2853-olaparib 
combination. 
Abiraterone acetate was selected based on the interim results of an ongoing randomized Phase 2 
clinical study comparing abiraterone acetate versus enzalutamide in patients with treatment-naïve 
mCRPC (Khalaf 2018). A PSA decline of more than 50% occurred in 34% of abiraterone acetate 
treated patients compared to 4% in the enzalutamide treated patients (p <0.001) after a median 
follow-up of 22.3 months. Additionally, the median time to PSA progression on 2nd-line therapy 
was 2.7 versus 1.3 months (hazard ration [HR] 0.38, 95% CI 0.26–0.56) in favor of abiraterone 
acetate. Lastly, the median OS was not reached versus 24.3 months (HR 0.82, 95% CI  
0.53–1.27) in favor of abiraterone acetate. 

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Olaparib was selected based on the PROfound study. The study was divided into two cohorts 
based on patient HRR status. Cohort A, patients with BRCA1/2 or ATM mutations, and 
Cohort B, patients based on 12 gene HRR signature excluding BRCA1/2 and ATM. A 
statistically significant improvement was demonstrated for olaparib compared to investigator’s 
choice in Cohort A for rPFS with a median of 7.4 months vs. 3.6 months (HR 0.34; 95% CI:  
0.25, 0.47; p <0.0001), for OS with a median of 19.1 months vs. 14.7 months (HR 0.69; 95% CI:  
0.50, 0.97, p = 0.0175) and for ORR 33% vs 2% (p <0.0001). A statistically significant 
improvement for olaparib compared to investigator’s choice was also demonstrated for rPFS in 
Cohort A+B, with a median of 5.8 months vs. 3.5 months (HR 0.49; 95% CI:  0.38, 0.63; 
p <0.0001). 
1.6 
Potential Risks and Benefits 
This study is intended to evaluate safety, PK, tolerability, and preliminary efficacy of PLX2853 
in combination with abiraterone acetate and PLX2853 in combination with olaparib. The 
identified risks of treatment with BET inhibitors from preclinical experience and other clinical 
development programs are hematologic toxicities, including thrombocytopenia, decreased white 
blood cell and red blood cell counts. Decrease of lymphatic tissue and lymphocytes may also 
contribute to increased risk of infection. Intestinal mucosal atrophy was observed with mucosal 
inflammation and hemorrhage as a possible consequence. Prolongation of coagulation times 
(aPTT, prothrombin time) was also observed nonclinically and lung inflammation with 
hemorrhage was reported. Testicular atrophy was also reported in nonclinical studies. In the 
nonclinical toxicology studies, following 28 days of treatment-free recovery, microscopic 
findings had either completely resolved or were considered to be in the process of resolving, 
demonstrating the potential for reversibility of these findings. Most of these parameters can be 
monitored for their appearance and followed in clinical studies. Nonclinical genotoxicity studies 
with PLX2853 (in vitro chromosomal aberration and in vivo rat micronucleus assays) identified 
chromosomal abnormalities indicating a potential for genotoxicity. Potential benefits for 
qualifying subjects with mCRPC include the opportunity to receive an experimental treatment 
that may increase the probability of clinical response, extend the duration of response, survival 
and/or symptomatic improvement. 
As of 30 June 2021, a total of 79 subjects have received PLX2853 monotherapy at doses ranging 
from 5 to 180 mg QD and 40 to 60 mg BID in Studies PLX124-01, PLX124-02, and PLX124-03. 
No treatment-related deaths have been reported. A total of 5 subjects have experienced DLTs, all 
with PLX2853 monotherapy. In PLX124-01, 3 DLTs were reported: 2 subjects experienced a 
DLT of Grade 4 thrombocytopenia at 120 mg QD. One of the thrombocytopenia events also had 
three treatment-related serious adverse events (SAEs) of embolism, ischemic stroke, and 
subarachnoid hemorrhage reported at the same time. One subject experienced Grade 3 fatigue, 
Grade 2 cheilitis, and Grade 2 nausea at 40 mg BID requiring a dose reduction in cycle 1, which 
is a DLT. In PLX124-02, 2 DLTs were reported: 1 event of Grade 3 hyperbilirubinemia at 
140 mg QD and one event of Grade 3 blood bilirubin increased at 180 mg QD. 

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The most common adverse events (AEs) associated with PLX2853 monotherapy reported in 
>10% of subjects are nausea, fatigue, diarrhea, anorexia, dysgeusia, vomiting, anemia, 
hyperbilirubinemia/blood bilirubin increased, and thrombocytopenia/platelet count decreased. 
Less common side effects recorded in >5% to 10% of subjects associated with PLX2853 are 
dizziness, dry mouth, gastroesophageal reflux disease, and leukopenia/white blood cell count 
decreased, hyponatremia, increased aspartate aminotransferase (AST), hyperglycemia, 
abdominal distension, dyspnea, hypophosphatemia, hypertension, prolonged aPTT, headache, 
hypokalemia, lymphopenia/lymphocyte count decreased, epistaxis, and weight decreased. 
As of 30 June 2021, a single fatal case of potential differentiation syndrome has been identified 
in a subject with relapsed acute myeloid leukemia treated with a bromodomain inhibitor 
(PLX51107) in a clinical study sponsored by Plexxikon. Thus, the treatment of hematological 
myeloid malignancies with PLX2853 carries a theoretical risk for differentiation syndrome. No 
events of differentiation syndrome were reported in study PLX124-02 (R/R AML and High-risk 
MDS). There is no known basis for this risk in solid tumors. 
Refer to the Reference Safety Information section of the Investigator’s Brochure and applicable 
labels for abiraterone acetate, prednisone, and/or olaparib, for additional safety information. 
1.7 
Previous Pharmacokinetics and Pharmacodynamics Experience 
1.7.1 
PLX2853 Clinical Pharmacokinetics 
As of 30 June 2021, exposure to PLX2853 has been evaluated in 4 clinical studies: PLX124-01, 
PLX124-02, PLX124-03, and PLX124-04. PLX2853 has been administered as a single agent in 
3 studies and in combination with carboplatin, abiraterone acetate, prednisone, and olaparib in 
2 studies.  
The PK of PLX2853 was evaluated in 46 subjects in PLX124-01 (solid tumors and lymphoma) 
at dose levels between 5 mg/day and 120 mg/day using once daily (QD) or twice daily (BID) 
dosing in the fasted state. The time to peak plasma concentration (Tmax) was approximately 1 
hour. Dose-dependent increases in exposures (Cmax and AUC0-24) were observed on both Day 1 
and Day 15 (steady-state). PK data indicated that QD and BID of the same total daily dose 
resulted in similar daily exposures. There was no significant accumulation observed at steady-
state, which is consistent with the short terminal half-life.  
The PK of PLX2853 was evaluated in 21 subjects in PLX124-02 (R/R AML and High-Risk 
MDS) at dose levels between 20 mg/day and 180 mg/day using QD dosing in the fasted state. 
Comparable exposures were achieved in Study PLX124-02 and Study PLX124-01. 
The PK of PLX2853 was evaluated in 17 subjects in PLX124-03 (advanced gynecological 
malignancies) at 80 mg QD monotherapy and at 40 mg QD and 80 mg QD in combination with 
carboplatin in the fasted state. Comparable exposures of PLX2853 were achieved in combination 
with carboplatin and as a single agent. 

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The PK of PLX2853 was evaluated in 3 subjects in PLX124-04 (mCRPC) at 40 mg QD in 
combination with abiraterone acetate and prednisone in the fasted state. Comparable exposures 
of PLX2853 were achieved in combination with abiraterone acetate and prednisone and as a 
single agent. 
1.7.2 
PLX2853 Clinical Pharmacodynamics 
As of 30 June 2021, PD data were available from 36 subjects enrolled in Study PLX124-01. 
Analysis of peripheral blood cells from subjects on Day 1 (before and after a single dose of 
PLX2853) demonstrated dose- and exposure-dependent changes in the expression of BET target 
genes. Figure 2 shows the dose response as measured by a 12-gene BET inhibitor responsive 
signature (the 12 genes are as follows:  HEXIM1, WDR47, GLS, G3BP1, CALM1, CIRBP, 
CCR1, CCR2, TNFRSF8, SCIMP, BTN3A2, and KMO). 
Figure 2: 
PLX2853 Pharmacodynamic Effect on Peripheral Blood Cells in 
Study PLX124-01 (Subjects with Solid Tumors) 
 
Of the 12 genes, 6 (HEXIM1, WDR47, GLS, G3BP1, CALM1, CIRBP) are up-regulated and 6 (CCR1, CCR2, 
TNFRSF8, SCIMP, BTN3A2, KMO) are down-regulated. The Y-axis shows the average of the absolute value of the 
Log2 fold change at 3 hours relative to baseline for the 12 genes. The figure above is plotted for Cycle 1 Day 1 data. 
The 40 and 60 mg dose levels include both once daily and twice daily dosing, where twice daily AUC0-24 was 
calculated as 2 × AUC0-12. 
Figure 3 shows the dose response as measured by a 12-gene BET inhibitor responsive signature 
in peripheral blood (Cycle 1 Day 1 [C1D1] 3 hours postdose versus C1D1 predose) and bone 
marrow (C2D1 3 hours postdose versus Screening) in PLX124-02 subjects. A robust PD 

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response in peripheral blood cells on C1D1 was measurable in all subjects at 3 hours postdose, 
with the highest responses observed at the 80 mg dose. Gene expression was also profiled in 
bone marrow aspirates that were collected at Screening and on C2D1, approximately 3 hours 
postdose. A consistent PD response was observed in the bone marrow cells of all 6 subjects on 
C2D1, but the magnitudes were not dose dependent.  
Figure 3: 
PLX2853 Pharmacodynamic Effect in Peripheral Blood and Bone 
Marrow Cells in PLX124-02 (AML/MDS) 
 
AML = acute myeloid leukemia; MDS = myelodysplastic syndrome; QD = once daily 
At the time of the cut-off, no PD data was available for PLX124-03 or PLX124-04. 

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2.0 
STUDY OBJECTIVES 
2.1 
PLX2853 + Abiraterone Acetate + Prednisone Combination 
2.1.1 
Phase 1b (Dose Escalation) 
The primary objective is as follows: 
• To evaluate the safety and tolerability of PLX2853 + abiraterone acetate + prednisone 
including dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and 
recommended Phase 2 dose (RP2D) in subjects with mCRPC who develop disease 
progression while currently receiving initial treatment with abiraterone acetate and 
prednisone 
The secondary objective is as follows: 
• To characterize the PK of PLX2853 and abiraterone and efficacy of PLX2853 combined with 
abiraterone acetate + prednisone in subjects with mCRPC who develop disease progression 
while currently receiving initial treatment with abiraterone acetate and prednisone 
 
2.1.2 
Phase 2a (Dose Expansion) 
The primary objective is as follows: 
• To evaluate the efficacy of PLX2853 + abiraterone acetate + prednisone at the RP2D in subjects 
with mCRPC who develop disease progression while currently receiving initial treatment with 
abiraterone acetate and prednisone 
The secondary objective is as follows: 
• To further characterize the safety and PK of PLX2853 and abiraterone when PLX2853 is 
combined with abiraterone acetate + prednisone in subjects with mCRPC who develop disease 
progression while currently receiving initial treatment with abiraterone acetate and prednisone 
 
2.2 
PLX2853 + Olaparib Combination 
2.2.1 
Phase 1b (Dose Escalation) 
The primary objective is as follows: 
• To evaluate the safety and tolerability of PLX2853 + olaparib including dose limiting 
toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) 
in subjects with deleterious or suspected deleterious germline or somatic homologous 
recombination repair (HRR) gene-mutated mCRPC who have progressed following prior 
treatment with abiraterone acetate and prednisone or with enzalutamide 

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The secondary objective is as follows: 
• To characterize the PK of PLX2853 and olaparib and efficacy of PLX2853 combined with 
olaparib in subjects with deleterious or suspected deleterious germline or somatic 
homologous recombination repair (HRR) gene-mutated mCRPC who have progressed 
following prior treatment with abiraterone acetate and prednisone or with enzalutamide 
 
2.2.2 
Phase 2a (Dose Expansion) 
The primary objective is as follows: 
• To evaluate the efficacy of PLX2853 + olaparib at the RP2D in subjects with deleterious or 
suspected deleterious germline or somatic homologous recombination repair (HRR) gene-
mutated mCRPC who have progressed following prior treatment with abiraterone acetate and 
prednisone or with enzalutamide 
The secondary objective is as follows: 
• To further characterize the safety and PK of PLX2853 and olaparib when PLX2853 is 
combined with olaparib in subjects with deleterious or suspected deleterious germline or 
somatic homologous recombination repair (HRR) gene-mutated mCRPC who have 
progressed following prior treatment with abiraterone acetate and prednisone or with 
enzalutamide 
 
2.3 
Exploratory Objectives (Both Phases, Both Combinations) 
The exploratory objectives are as follows: 
• To assess biomarkers in peripheral blood cells, tumor cells, and tissue biopsies 
• To further evaluate the pharmacodynamics (PD) of PLX2853 

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3.0 
STUDY DESIGN 
3.1 
PLX2853 + Abiraterone Acetate + Prednisone Combination Therapy 
This multicenter, open-label, 2-part study will evaluate the safety, PK, PD, and efficacy of 
PLX2853 + abiraterone acetate + prednisone combination therapy in subjects with mCRPC who 
develop disease progression, while currently receiving initial abiraterone acetate and prednisone 
therapy, as documented by radiographic imaging, prostate-specific antigen (PSA), or clinical 
assessment. The study schema is presented in Figure 4. 
Figure 4: 
Study Schema, PLX2853 + Abiraterone Acetate + Prednisone 
Combination Therapy 
 
QD = once daily; RP2D = recommended Phase 2 dose 
 
3.1.1 
Phase 1b – Determination of RP2D of PLX2853 in Combination with 
Abiraterone Acetate and Prednisone 
The safety, PK, PD, and efficacy of the combination of PLX2853 + abiraterone acetate + 
prednisone will be evaluated. The study population is patients with mCRPC who develop disease 
progression while currently receiving initial abiraterone acetate therapy, as documented by 
radiographic imaging, prostate-specific antigen (PSA), or clinical assessment. The combination 
of PLX2853 + abiraterone acetate + prednisone will be administered daily in 21-day treatment 
cycles. A standard “3+3” dose-escalation design will be followed. The starting dose level 
(Cohort 1) of PLX2853 will be 40 mg, which is 50% below the PLX2853 monotherapy RP2D of 
80 mg/day defined in study PLX124-01 (NCT03297424). PLX2853 will be administered once 
daily + abiraterone acetate 1000 mg orally once daily + prednisone 5 mg orally twice daily. Note 

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that the doses of abiraterone acetate and prednisone are fixed and will not be modified. See 
Section 5.4 for a full description of the dose escalation plan. 
3.1.2 
Phase 2a – Dose Expansion for Combination of PLX2853 + Abiraterone + 
Prednisone 
In Phase 2a (dose expansion), efficacy as well as additional safety, PK, and PD information of 
PLX2853 in combination with abiraterone acetate and prednisone at the RP2D dose established 
in Phase 1b by the Study Committee will be obtained using a Simon’s 2-stage design. 
Initially, 9 subjects will be enrolled to assess for efficacy in Phase 2a. If 2 or more responses are 
observed in the first 9 evaluable subjects, an additional 10 evaluable subjects will be enrolled. 
Subjects in Phase 2a who do not complete their 12-week disease response assessment for reasons 
other than toxicity or disease progression may be replaced. 
3.1.3 
Pharmacokinetics of PLX2853 and Abiraterone 
PLX2853 and abiraterone PK data will be analyzed in each dosing cohort for maximum observed 
concentration (Cmax), AUC, and accumulation at steady state and compared with prior dose 
levels. The number of subjects at a given dose level may be increased as a result of the review of 
safety, observed or anticipated disease activity, and PK data. Additional dosing schedules of 
PLX2853 in combination with abiraterone acetate and prednisone may be studied, such as 
alternate-day dosing (e.g., every other day) depending on emerging safety and PK data for the 
combination. 
3.2 
PLX2853 + Olaparib Combination Therapy 
This multicenter, open label 2-part study will evaluate the safety, PK, PD, and efficacy of 
PLX2853 + olaparib combination therapy in subjects with deleterious or suspected deleterious 
germline or somatic homologous recombination repair (HRR) gene-mutated mCRPC who have 
progressed, as documented by radiographic imaging, prostate-specific antigen (PSA), or clinical 
assessment, following prior treatment with abiraterone acetate and prednisone or with 
enzalutamide. This combination will only be investigated in regions where olaparib is approved. 
This combination will only be investigated in regions where olaparib is approved. The study 
schema is presented in Figure 5. 

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Figure 5: 
Study Schema, PLX2853 + Olaparib Combination Therapy 
 
QD = once daily; RP2D = recommended Phase 2 dose 
 
3.2.1 
Phase 1b – PLX2853 + Olaparib 
The safety, PK, PD, and efficacy of PLX2853 + olaparib will be evaluated. The study population 
is patients with deleterious or suspected deleterious germline or somatic homologous 
recombination repair (HRR) gene-mutated mCRPC who have progressed following prior 
treatment with abiraterone acetate and prednisone or with enzalutamide, as documented by 
radiographic imaging, prostate-specific antigen (PSA), or clinical assessment. This combination 
will only be investigated at U.S. sites. The combination of PLX2853 + olaparib will be 
administered daily in 21-day treatment cycles. A standard “3+3” dose-escalation design will be 
followed. The starting dose level (Cohort 1) of PLX2853 will be 40 mg, which is 50% below the 
PLX2853 monotherapy RP2D of 80 mg/day defined in study PLX124-01 (NCT03297424). 
PLX2853 will be administered once daily + olaparib 600 mg (300 mg twice daily). Note that the 
dose of olaparib is fixed and will not be modified. See Section 5.4 for a full description of the 
dose escalation plan. 
3.2.2 
Phase 2a – Dose Expansion for Combination of PLX2853 + Olaparib 
In Phase 2a (dose expansion), efficacy as well as additional safety, PK, and PD information of 
PLX2853 in combination with olaparib at the RP2D dose established in Phase 1b by the Study 
Committee will be obtained using a Simon’s 2-stage design. 
Initially, 28 subjects will be enrolled to assess for efficacy in Phase 2a. If 16 or more responses 
are observed in the first 28 evaluable subjects, an additional 30 evaluable subjects will be 

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enrolled. Subjects in Phase 2a who do not complete their 12-week disease response assessment 
for reasons other than toxicity or disease progression may be replaced. 
3.2.3 
Pharmacokinetics of PLX2853 and Olaparib 
PLX2853 and olaparib PK data will be analyzed in each dosing cohort for Cmax, AUC, and 
accumulation at steady state and compared with prior dose levels. The number of subjects at a 
given dose level may be increased as a result of the review of safety, observed or anticipated 
disease activity, and PK data. Additional dosing schedules of PLX2853 in combination with 
olaparib may be studied, such as alternate-day dosing (e.g., every other day) depending on 
emerging safety and PK data for the combination. 
3.3 
Number of Subjects 
Up to 110 evaluable subjects will be enrolled. 
PLX2853 + Abiraterone Acetate + Prednisone Combination 
 
Phase 1b:  Up to 15 evaluable subjects 
• Approximately 9 to 15 evaluable subjects with mCRPC who develop disease progression 
while currently receiving initial treatment with abiraterone acetate and prednisone 
 
Phase 2a (Dose Expansion):  Up to 19 evaluable subjects 
• There will be a single Simon’s 2-stage design cohort of between 9 to 19 evaluable 
subjects with mCRPC who develop disease progression while currently receiving initial 
treatment with abiraterone acetate and prednisone 
 
PLX2853 + Olaparib Combination 
Phase 1b:  Up to 18 evaluable subjects 
• Approximately 9 to 18 evaluable subjects, with deleterious or suspected deleterious 
germline or somatic homologous recombination repair (HRR) gene-mutated mCRPC 
who have progressed following prior treatment with abiraterone acetate or enzalutamide. 
Phase 2a (Dose Expansion):  Up to 58 evaluable subjects 
• There will be a single Simon’s 2-stage design cohort of between 28 to 58 evaluable 
subjects with deleterious or suspected deleterious germline or somatic homologous 
recombination repair (HRR) gene-mutated mCRPC who have progressed following prior 
treatment with abiraterone acetate or enzalutamide 
 

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3.4 
Duration of Study 
The study encompasses the following periods: 
• Screening Period:  Up to 28 days prior to the first dose of study drug. 
• Treatment Period:  Daily in 21-day cycles until subject discontinuation or withdrawal or 
study termination (see Section 7.1.5). 
• 30-day Follow-up (FU) Visit:  Approximately 30 days after the last dose of study drug 
or prior to starting any new anti-cancer therapy, whichever occurs first. 
• Long-term Follow-up Period:  Subjects will be followed until death, withdrawal of 
consent, or loss to follow-up according to the following schedule: 
– First two years after the 30-day FU Visit – Every 3 months 
– Third year after the 30-day FU Visit and beyond – Every 6 months 
– Survival follow-up can be via clinic visit, phone call to the subject or referring 
physician, or other method deemed appropriate by the site and should assess survival, 
progression, subsequent therapy, and response. 
• Any subject with a confirmed response who discontinues treatment for reasons other than 
disease progression will continue to be followed per standard of care and no less than 
every 3 months until documented disease progression, initiation of a new anti-cancer 
treatment, or 1 year from discontinuation of study treatment. Response assessment in 
follow up will include at minimum the modality used to determine response (radiographic 
imaging, PSA, and/or CTC assessment) 
 
3.5 
Endpoints 
3.5.1 
PLX2853 + Abiraterone Acetate + Prednisone Combination 
3.5.1.1 
Phase 1b – Primary Endpoint 
Primary Endpoint: 
• Incidence of DLTs, TEAEs, changes in safety parameters, and unacceptable toxicities 
 
3.5.1.2 
Phase 2a – Primary Endpoints 
Primary Endpoints: 
• Response as defined by any of the outcomes listed below. If any of these occur, the subject 
will be considered to have responded. 
• Objective response by per RECIST v1.1 with a minimum interval for confirmation of CR 
and PR of 4 weeks 

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• PSA decline of ≥50% from baseline, confirmed by a second consecutive PSA assessment 
at least 3 weeks later 
• Conversion of circulating tumor cell count (CTC) to <5 cells/7.5 mL blood nadir 
confirmed by an additional assessment at least 3 weeks later (for subjects with a CTC 
count of ≥5 cells/7.5 mL blood at baseline) 
 
3.5.2 
PLX2853 + Olaparib Combination 
3.5.2.1 
Phase 1b – Primary Endpoint 
Primary Endpoint: 
• Incidence of DLTs, TEAEs, changes in safety parameters, and unacceptable toxicities 
 
3.5.2.2 
Phase 2a – Primary Endpoint 
Primary Endpoint: 
• Response as defined by any of the outcomes listed below. If any of these occur, the subject 
will be considered to have responded. 
• Objective response by modified RECIST v1.1 with a minimum interval for confirmation 
of CR and PR of 4 weeks 
• PSA decline of ≥50% from baseline, confirmed by a second consecutive PSA assessment 
at least 3 weeks later 
• Conversion of circulating tumor cell count (CTC) to <5 cells/7.5 mL blood nadir 
confirmed by an additional assessment at least 3 weeks later (for subjects with a CTC 
count of ≥5 cells/7.5 mL blood at baseline) 
 
3.5.3 
Both Phases, Both Combinations 
3.5.3.1 
Both Phases – Secondary Endpoints 
Secondary Endpoints: 
• Radiographic progression-free survival (rPFS) 
• Time to PSA progression 
• Duration of PSA response 
• Overall survival defined as the time from the first dose of study drug to the date of death due 
to any cause 
• Incidence of TEAEs, changes in safety parameters, and unacceptable toxicities 

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• PK parameters of PLX2853 and abiraterone and PLX2853 and olaparib following single and 
repeated dosing 
• BOR per RECIST v1.1 
• DOR (time from date of first documented, confirmed response using RECIST v1.1 and 
PCWG3 until date of documented progression or death from any cause). 
• Time to first SSRE defined as: 
• Use of radiation therapy to prevent or relieve skeletal symptoms. 
• Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral). 
Radiologic documentation is required. 
• Occurrence of spinal cord compression. Radiologic documentation required. 
• Orthopedic surgical intervention for bone metastasis. 
 
3.5.3.2 
Both Phases – Exploratory Endpoints 
Exploratory Endpoints: 
• Analysis of peripheral blood cells for dose- and exposure-dependent changes in the 
expression of BET target genes as measured by a 12-gene BET inhibitor responsive signature 
• Pharmacodynamic assessments for potential biomarkers 
 
3.6 
Randomization 
None of the subjects in this study will be randomized. 

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4.0 
STUDY POPULATION 
Subjects must meet the following inclusion and not meet the following exclusion criteria to be 
enrolled in the study. 
4.1 
Inclusion Criteria 
Inclusion Criteria Applicable to Both Combinations: 
1. Age ≥18 years at the time of signing informed consent. 
2. Histologically confirmed adenocarcinoma of the prostate with tumor tissue available for 
molecular analyses. 
3. Serum testosterone level of <50 ng/dL (<2.0 nM) assessed within 28 days of C1D1 and 
surgically or medically castrated and/or receiving treatment with an LHRH/GnRH analogue 
(agonist/antagonist).  
4. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue 
(agonist/antagonist) or have received an orchiectomy. If receiving primary androgen 
deprivation therapy, this therapy must have been initiated at least 28 days prior to start of 
study dosing and must be continued throughout the study. 
5. Eastern Cooperative Oncology Group Performance Status 0 to 1. 
6. Adequate organ function as demonstrated by the following laboratory values. All Screening 
laboratory tests should be performed within 10 days prior to the first PLX2853 dose. 
 Hematological: 
 Neutrophils ≥1500/µL. 
 Platelets ≥100,000/µL (transfusion not permitted within 28 days prior to screening 
blood draw for olaparib, 14 days for abiraterone). 
 Hemoglobin ≥9 g/dL (transfusion and erythropoietin not permitted within 28 days 
prior to screening blood draw for olaparib, 14 days for abiraterone). 
 Renal: 
 Measured (by 24-hour urine collection) or calculated Creatinine Clearance (CrCL) 
>50 mL/min. The Cockcroft-Gault formula should be used for calculation 
(Appendix 1). 
 Hepatic: 
 Serum total bilirubin ≤1.5 × upper limit of normal (ULN). 
Exception for elevated bilirubin secondary to Gilbert’s disease. Confirmation of 
Gilbert’s diagnosis requires:  elevated unconjugated (indirect) bilirubin values; 
normal complete blood count in previous 12 months, blood smear, and reticulocyte 
count; normal aminotransferases and alkaline phosphatase in previous 12 months. 
 Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2 × ULN. 
For subjects with metastatic liver metastases ≤2.5 × ULN. 

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 Coagulation: 
 International normalized ratio (INR) ≤1.5 × ULN. 
 Activated partial thromboplastin time (aPTT) ≤1.5 × ULN. 
 Chemistry: 
 Albumin ≥3.0 g/dL. 
7. Fertile male subjects with female sexual partners must agree to use a highly effective 
method of birth control (defined in Section 4.2.1) during the study and for 90 days after the 
last dose of study drug. 
8. Except as specified above for organ function, all drug-related toxicity from previous cancer 
therapy (including ongoing abiraterone acetate + prednisone therapy if applicable) must be 
resolved (to Grade ≤1 or baseline per National Cancer Institute Common Terminology 
Criteria for Adverse Events version 5.0) prior to study treatment administration (Grade 2:  
alopecia, hot flashes, decreased libido, or neuropathy is allowed). 
9. Willingness and ability to provide written informed consent prior to any study-related 
procedures and to comply with all study requirements. 
Inclusion Criteria Applicable to PLX2853 + Abiraterone Acetate + Prednisone 
Combination: 
10. Currently receiving initial abiraterone acetate 1000 mg QD and prednisone per the 
abiraterone acetate label as most recent systemic therapy for mCRPC and showing evidence 
of progression as assessed by the investigator with one or more of the following (subjects 
who begin treatment in the hormone sensitive setting and progress to mCRPC and have not 
discontinued their initial abiraterone acetate treatment are not excluded). Subjects must be 
on a stable dose of prednisone for at least 14 days prior to C1D1: 
a. PSA progression defined, per PCWG3 criteria (Scher 2016; Appendix 6) at trial entry, as 
≥2 occurrences of rising PSA levels with a minimum interval of 1 week and a PSA 
concentration of ≥1 ng/mL if confirmed PSA rise is the only measure of progression. 
b. Worsening measurable disease on CT/MRI per RECIST v1.1 criteria or at least one new 
documented bone lesion on a bone scan. 
11. Potassium within normal limits. 
Inclusion Criteria Applicable to PLX2853 + Olaparib Combination: 
12. Prior genetic testing completed with known deleterious or suspected deleterious germline or 
somatic homologous recombination repair (HRR) gene-mutation per FDA label for mCRPC 
as defined by an FDA-approved companion diagnostic (HRR mutation must be known prior 
to consent). 
13. Prior treatment with abiraterone acetate and/or enzalutamide for metastatic prostate cancer 
and/or CRPC. 
14. Evidence of radiographic progression of metastatic disease at study entry as assessed by the 
investigator defined as measurable disease on CT/MRI per RECIST v1.1 criteria or at least 
one documented bone lesion on a bone scan. Subjects whose disease spread is limited to 
regional pelvic lymph nodes or local recurrence (e.g., bladder, rectum) are not eligible. 

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4.2 
Exclusion Criteria 
Exclusion Criteria Applicable to Both Combinations: 
1. Prior exposure to a bromodomain inhibitor. 
2. Ongoing systemic infection requiring antibiotic, antiviral, or antifungal treatment. 
3. History of autoimmune hemolytic anemia or autoimmune thrombocytopenia. 
4. Presence of symptomatic or uncontrolled central nervous system or leptomeningeal 
metastases. 
Note:  Subjects with stable, treated brain metastases are eligible for this study. However, 
subjects must not have required steroid treatment for their brain metastases within 30 days 
of Screening. 
5. Symptomatic or impending cord compression unless appropriately treated beforehand and 
clinically stable and asymptomatic. 
6. Known or suspected allergy to the investigational agent or any agent given in association 
with this study. 
7. Clinically significant cardiac disease, defined as any of the following: 
 Clinically significant cardiac arrhythmias including bradyarrhythmias and/or subjects 
who require anti-arrhythmic therapy (excluding beta blockers or digoxin). Subjects with 
controlled atrial fibrillation are not excluded. 
 Congenital long QT syndrome or subjects taking concomitant medications known to 
prolong the QT interval (Drugs with a low risk of QTc prolongation that are needed for 
infection control or nausea may be permitted with approval from the Medical Monitor). 
A list of drugs known to prolong the QT interval and risk of TdP can be found in 
Appendix 4. 
 QTcF ≥450 msec at Screening (based on average of triplicate ECGs at baseline). 
 If the QTc is prolonged in a subject with a pacemaker or bundle branch block, the 
subject may be enrolled in the study if confirmed by the medical monitor. 
 History of clinically significant cardiac disease or congestive heart failure >New York 
Heart Association Class II or left ventricular ejection fraction measurement of <50% at 
baseline. Subjects must not have unstable angina (anginal symptoms at rest) or new-
onset angina within the last 3 months or have had a coronary artery bypass, angioplasty, 
vascular stent, or myocardial infarction within the past 6 months. 
 Uncontrolled hypertension, defined as systolic blood pressure >160 mmHg or diastolic 
blood pressure >100 mmHg which has been confirmed by 2 successive measurements 
despite optimal medical management. 

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 Arterial or venous thrombotic or embolic events such as cerebrovascular accident 
(including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism 
within the 3 months before start of study medication (except for adequately treated 
catheter-related venous thrombosis occurring >1 month before the start of study 
medication). 
8. Inability to take oral medication or significant nausea and vomiting, malabsorption, or 
significant small bowel resection that, in the opinion of the Investigator, would preclude 
adequate absorption. 
9. Non-healing wound or ulcer. 
10. Infection with HIV-1 or HIV-2. Exception:  subjects with well-controlled HIV (e.g., CD4 
>350/mm3 and undetectable viral load) are eligible. 
11. Current active liver disease from any cause, including hepatitis A (hepatitis A virus 
immunoglobulin M positive), hepatitis B (hepatitis B virus [HBV] surface antigen positive), 
or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCV ribonucleic 
acid). Subjects with HCV with undetectable virus after treatment are eligible. Subjects with 
a prior history of HBV are eligible if quantitative PCR for HBV DNA is negative. These 
subjects must be willing to undergo additional testing per local standard of care. 
12. Baseline moderate or severe hepatic impairment (Child-Pugh Class B and C). 
13. Active known second malignancy with the exception of any of the following: 
 Adequately treated basal cell carcinoma or squamous cell carcinoma of the skin. 
 Adequately treated Stage I cancer from which the subject is currently in remission and 
has been in remission for ≥2 years. 
 Any other cancer from which the subject has been disease-free for ≥3 years. 
14. Major surgery or significant traumatic injury within 28 days of Cycle 1 Day 1. 
15. Currently receiving medications known to be strong or moderate inducers or inhibitors of 
CYP3A4 and substrates of CYP2D6 with a narrow therapeutic window (Appendix 2). These 
strong and moderate inducers, inhibitors and substrates must be discontinued at least 7 days 
prior to the first administration of study drug). 
16. Use of biotin (i.e., Vitamin B7) or supplements containing biotin higher than the daily 
adequate intake of 30 µg (NIH-ODS 2020). Note:  Subjects who switch from a high dose to 
a dose of 30 µg/day or less are eligible for study entry. 
17. Any chronic medical condition requiring a dose of corticosteroids greater than 10 mg 
prednisone/prednisolone daily. 
18. Use of herbal, alternative and food supplements (i.e., PC-Spes, Saw Palmetto, St. John’s 
Wort, etc.) and probiotics must be discontinued before treatment start. Daily Multi-vitamin 
(provided it does not contain biotin >30 μg/day), calcium, and Vitamin D are permitted. 

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19. Subjects with a history of adrenal insufficiency, hyperaldosteronism, or pituitary 
dysfunction. 
20. Poorly controlled known type 2 diabetes with HbA1C >7.5% (must be assessed within 
28 days of C1D1 for any subject with known or suspected type 2 diabetes). 
21. Live vaccine within 4 weeks of starting treatment. 
22. Treatment with warfarin within 7 days of C1D1. 
23. Subject is participating in any other therapeutic clinical study (observational or registry 
studies are allowed). 
24. Presence of any other medical, psychological, familial, sociological, or geographic condition 
potentially hampering compliance with the study protocol or would interfere with the study 
endpoints or the subject’s ability to participate in the study in the judgment of the 
Investigator. 
Exclusion Criteria Applicable to PLX2853 + Abiraterone Acetate + Prednisone 
Combination: 
25. Receipt of any anti-cancer therapy prior to Cycle 1 Day 1 with the exception of abiraterone 
acetate and GnRH therapy: 
 Prior systemic chemotherapy in the setting of mCRPC is not permitted (prior 
chemotherapy in the hormone-sensitive setting is allowed provided last dose was at least 
6 months prior to Cycle 1 Day 1). Prior chemotherapy for any other disease within 
2 years is prohibited. 
 Radiation therapy within 14 days prior to Cycle 1 Day 1. 
 Small molecule anti-cancer therapy for the treatment of cancer within 14 days or 5 half-
lives (whichever is shorter) prior to Cycle 1 Day 1. 
 Immunotherapy or other biologic therapy (e.g., monoclonal antibodies, antibody-drug 
conjugates) for the treatment of cancer within 21 days or 5 half-lives (whichever is 
shorter) prior to Cycle 1 Day 1. 
 5-α reductase inhibitors (e.g., finasteride, dutasteride), estrogen compounds (including 
estramustine) and megesterol are considered to be anti-cancer agents and prohibited 
within 21 days or 5 half-lives (whichever is shorter) prior to Cycle 1 Day 1. 
Note:  Subjects can receive a stable dose of bisphosphonates or denosumab for bone 
metastases before and during the study, as long as these were started at least 4 weeks prior to 
treatment with study drug. 
Exclusion Criteria Applicable to PLX2853 + Olaparib Combination: 
26. A medical history that includes any of myelodysplastic syndrome, monoclonal gammopathy 
of undetermined significance or acute myeloid leukemia. 

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27. Receipt of any anti-cancer therapy prior to Cycle 1 Day 1 with the exception of GnRH 
therapy: 
 Radiation therapy within 14 days prior to Cycle 1 Day 1. 
 Small molecule anti-cancer therapy for the treatment of cancer within 14 days or 5 half-
lives (whichever is shorter) prior to Cycle 1 Day 1. 
 Immunotherapy or other biologic therapy (e.g., monoclonal antibodies, antibody-drug 
conjugates) for the treatment of cancer within 21 days or 5 half-lives (whichever is 
shorter) prior to Cycle 1 Day 1. 
 5-α reductase inhibitors (e.g., finasteride, dutasteride), estrogen compounds (including 
estramustine) and megesterol are considered to be anti-cancer agents and prohibited 
within 21 days or 5 half-lives (whichever is shorter) prior to Cycle 1 Day 1. 
 Prior treatment with DNA-damaging cytotoxic chemotherapy (including platinum-based 
agents, cyclophosphamide, and mitoxantrone) is excluded with the exception of 
estramustine. Non-DNA-damaging chemotherapy (docetaxel, cabazetaxel, etc.) within 
14 days or 5 half-lives (whichever is shorter) is excluded. Any chemotherapy not listed 
requires Medical Monitor review and approval to confirm eligibility. 
Note:  Subjects can receive a stable dose of bisphosphonates or denosumab for bone 
metastases before and during the study as long as these were started at least 4 weeks prior to 
treatment with study drug. 
28. Prior exposure to a PARP inhibitor. 
 
4.2.1 
Birth Control Methods 
Fertile male subjects with female sexual partners must agree to use two forms of approved 
contraception (i.e., a highly effective method of hormonal/intrauterine contraception with a 
failure rate <1% per year and 1 additional barrier method) during the study to 90 days after the 
last dose of study drug according to the below list: 
Barrier Methods 
Hormonal/Intrauterine Methodsa 
Male or female condom with or without 
spermicide 
Cap, diaphragm, or sponge each with 
spermicide 
Implants 
Hormone shot or injection 
Combined pill 
Patch 
Copper T intrauterine device or levonorgestrel-
releasing intrauterine system (e.g., Mirena®) 
a 
Highly effective (failure rate of <1% per year). 
 
Subjects with a pregnant or breast-feeding partner should use barrier method contraception 
(condom plus spermicidal gel). 

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5.0 
STUDY TREATMENTS 
5.1 
Investigational Product and Test Article Properties 
5.1.1 
PLX2853 (Investigational Product) 
PLX2853 is formulated as 20 mg strength tablets for oral use. The active drug substance is 
PLX2853, with additional excipients of hypromellose acetate succinate, copovidone, 
microcrystalline cellulose, mannitol, croscarmellose sodium, silicon dioxide, sodium stearyl 
fumarate, sodium bicarbonate, and poloxamer. The drug product presentation is a white to 
off -white solid tablet. The tablets are embossed with “PLX” on one side. 
5.1.2 
Abiraterone Acetate (Test Article) 
Abiraterone acetate 500 mg film-coated tablets are formulated with colloidal silicon dioxide, 
croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, silicified 
microcrystalline cellulose, and sodium lauryl sulfate (ZYTIGA®). The film-coating contains iron 
oxide black, iron oxide red, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. 
Abiraterone acetate 250 mg uncoated tablets are formulated with colloidal silicon dioxide, 
croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, 
povidone, and sodium lauryl sulfate. 
5.1.3 
Prednisone (Test Article) 
Prednisone tablets 5 mg may contain the following inactive ingredients:  anhydrous lactose, 
colloidal silicon dioxide, crospovidone, D&C Yellow No.10, docusate sodium, FD&C Yellow 
No. 6, magnesium stearate and sodium benzoate. 
An equivalent approved steroid may be used where applicable (prednisolone is acceptable; other 
equivalent agents must be approved by Plexxikon Medical Monitor). 
5.1.4 
Olaparib (Test Article) 
Olaparib tablets are available in 2 strengths, 100 mg and 150 mg. Both tablet strengths contain 
the following inactive ingredients:  copovidone, mannitol, colloidal silicon dioxide, and sodium 
stearyl fumarate. The tablets are coated using hyperomellose, PEG-400, titanium dioxide, ferric 
oxide, and ferrosoferric oxide only in the 150 mg tablet strength. Please refer to the 
LYNPARZA® label for additional information. 
5.2 
Study Drug Administration 
5.2.1 
PLX2853 Administration 
PLX2853 is formulated as 20-mg strength tablets for oral use. Subjects should fast for 2 hours 
before and 1 hour after taking PLX2853 (See Section 5.2.3) Tablets will be taken orally with 
water. PLX2853 should be taken at approximately the same time each day. PLX2853 tablets 

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should be swallowed whole and not crushed, chewed, or dissolved in water. A dosing period of 
up to 30 minutes is permissible if required by the number of tablets to be taken or as convenient 
for the subject. Missed doses (generally outside of a 2-hour dosing window) should be skipped 
and not administered as a double dose at the next administration. Subjects who omit their dose 
should be instructed NOT to make up that dose. Doses that are vomited should not be replaced. 
Subjects will be treated with PLX2853 for 21-day cycles. Guidance for dose modification is in 
Section 6.2. 
5.2.2 
Abiraterone Acetate Administration 
Abiraterone acetate 1000 mg is administered orally once daily in combination with prednisone 
5 mg administered orally twice daily. Abiraterone acetate (ZYTIGA® or generic equivalent) is 
available as either 500 mg film-coated tablets or 250 mg uncoated tablets. Abiraterone acetate 
must be taken on an empty stomach. No food should be consumed for at least 2 hours before the 
dose of abiraterone acetate is taken and for at least 1 hour after the dose of abiraterone acetate is 
taken. The tablets should be swallowed whole with water and not be crushed or chewed. Please 
refer to the ZYTIGA® FDA label or SmPC for additional information. 
PLX2853 and abiraterone acetate should be taken at the same time. 
5.2.3 
Prednisone Administration 
Prednisone 5 mg tablets are administered per the label for abiraterone acetate. Prednisone is 
recommended to be taken with food or milk at least 2 hours before PLX2853 and abiraterone 
acetate or 1 hour after taking PLX2853 and abiraterone acetate, except for PK collection days 
when subjects should take prednisone with food or milk at least 1 hour after taking PLX2853 and 
abiraterone acetate. An equivalent approved steroid may be used where applicable (prednisolone 
is acceptable; other equivalent agents must be approved by the Plexxikon Medical Monitor). 
5.2.4 
Olaparib Administration 
Olaparib 300 mg is administered orally twice daily. The morning dose of olaparib should be 
taken at the same time as PLX2853 and subjects should fast for at least 2 hours before and 1 hour 
after taking PLX2853 and olaparib. The evening olaparib dose may be taken with or without 
food. The tablets should be swallowed whole with water and not be chewed, crushed, dissolved, 
or divided. Please refer to the LYNPARZA® FDA label for additional information. 
5.2.5 
Dosing on PK Sample Collection Days 
On PK sample collection days, subjects should be instructed not to take their morning dose of 
PLX2853, abiraterone acetate, and prednisone, or PLX2853 and olaparib at home before the 
clinic visit. The time of dosing will be recorded in the clinic. Subjects should fast at least 2 hours 
before dose administration and 1 hour after administration of PLX2853 and abiraterone acetate 
or PLX2853 and olaparib. On PK days, prednisone should be taken at least 1 hour after taking 

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PLX2853 and abiraterone. On non-PK sample collection days, the subject will take PLX2853 
and abiraterone acetate or PLX2853 and olaparib at the same time independently, and (for 
abiraterone combo subjects) prednisone should be taken at least 2 hours before or 1 hour after 
taking PLX2853 and abiraterone acetate. Dosing information should be recorded in the study 
drug administration diary. 
5.3 
PLX2853 Dose Escalation 
In Phase 1b dose escalation for both combinations, cohorts will be enrolled using a standard 
“3+3” design. The starting dose level of PLX2853 will be 40 mg administered orally once daily 
taken in combination with either abiraterone acetate 1000 mg administered orally once daily and 
prednisone 5 mg administered orally twice daily, or olaparib 300 mg administered orally twice 
daily. In the absence of a DLT in the first cycle of treatment and in conjunction with review of 
the PK and available pharmacodynamics data from each cohort by the Study Committee, dose 
escalation of PLX2853 is planned to occur in the following manner: 
• DLTs will be assessed in the first treatment cycle. 
• The starting dose of PLX2853 will be 40 mg/day (Cohort 1), which is 50% below the 
PLX2853 monotherapy RP2D of 80 mg/day. 
• If Dose Level 1 is not tolerated, Dose Level -1 (20 mg/day) will be investigated. If that dose 
level is intolerable, the study will be halted. 
 
5.4 
Dose Escalation Plan 
5.4.1 
Dose Escalation Plan for the Combination of PLX2855 + Abiraterone Acetate + 
Prednisone 
The combination of PLX2853 + abiraterone acetate + prednisone will be administered daily in 
21-day treatment cycles. A standard “3+3” dose-escalation design will be followed. Three dose 
levels of PLX2853 are planned (Table 4). The starting dose level (Cohort 1) of PLX2853 will be 
40 mg, which is 50% below the PLX2853 monotherapy RP2D of 80 mg/day defined in study 
PLX124-01 (NCT03297424). PLX2853 will be administered once daily + abiraterone acetate 
1000 mg orally once daily + prednisone 5 mg orally twice daily. Note that the starting doses of 
abiraterone acetate and prednisone are fixed and will not be modified. 

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Table 4: 
Provisional PLX2853 Dose Escalation Plan for the Combination of PLX2853 
+ Abiraterone Acetate + Prednisone 
Provisional Dose Escalation Plan 
Dose 
Level 
PLX2853 Dose 
(mg/day)a 
Abiraterone Acetate Dose 
(mg/day)a 
Prednisone Dose  
(total mg/day)b 
-1 
20 
1000  
10 
1 
40 
1000  
10 
2 
80 
1000  
10 
a 
Once daily (QD) dosing schedule unless otherwise specified. Initial cohort will assess QD dosing. Subsequent 
cohorts may evaluate alternative dosing regimens as agreed to by the Study Committee. 
b 
5 mg twice daily (BID) dosing schedule. 
 
DLTs will be assessed in the first 21-day treatment cycle. In the absence of a DLT and in 
conjunction with review of the safety, PK, and available PD data from each dose cohort by the 
Study Committee, dose escalations are planned to occur in the following manner: 
• A minimum of 3 to 4 subjects will be initially enrolled in Dose Level 1 (Cohort 1). 
• If a DLT is observed in 1 subject in a given cohort, up to 6 subjects will be treated at that 
dose. 
• If DLTs are observed in 2 or more subjects (or ≥33% of the cohort) at a dose level, the dose 
at which this occurs will be considered intolerable and the MTD to have been exceeded. The 
highest dose level at which 0 or 1 of 6 subjects experience a DLT will be declared the RP2D. 
• If Dose Level 1 is not tolerated, Dose Level -1 (20 mg/day) will be studied. If that dose level 
is intolerable, the study will be halted. 
• At least 6 subjects must be evaluable at a given dose level in order to be considered an 
RP2D. 
• An RP2D may be declared at a dose level without reaching an MTD if further dose escalation 
is deemed unwarranted. 
• Any subject who misses more than 25% of doses in Cycle 1 (e.g., ≥ 6 doses of PLX2853 in 
21 days) for reasons other than a treatment-related AE, or is withdrawn from the study prior 
to completing Cycle 1 for reasons other than a DLT, will not be DLT evaluable and 
additional subject(s) may be enrolled to provide adequate data for dose escalation decision 
making.  
After dosing has been completed in each cohort, safety, PK data, and PD data (if available) will 
be reviewed, and dose escalation decisions will be made by the Study Committee. Dose 
escalation decisions will also take into consideration safety information beyond the DLT period 
from earlier cohorts. If no DLT is observed, the recommended dose for further evaluation may 
be established based on toxicity, PK, convenience of dosing, and PD (if available) in subjects 
treated at that dose. Dose escalation will only be permitted if adequate safety and tolerability 

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have been demonstrated at the previous lower dose for 21 days. Once all ongoing subjects in a 
dose cohort have been treated for at least two 21-day cycles and the safety and tolerability of that 
dose level has been established, intra-subject dose escalation to that dose level may be permitted 
for subjects enrolled at lower dose levels who have not experienced a Grade 3 or higher 
treatment-related toxicity and have completed 2 cycles of PLX2853. Any intra-subject dose 
escalation requires a discussion and agreement with the Medical Monitor. 
5.4.2 
Dose Escalation Plan for Combination of PLX2853 + Olaparib 
The combination of PLX2853 + olaparib will be administered daily in 21-day treatment cycles. 
A standard “3+3” dose-escalation design will be followed. Three dose levels of PLX2853 are 
planned (Table 5). The starting dose level (Cohort 1) of PLX2853 will be 40 mg, which is 50% 
below the PLX2853 monotherapy RP2D of 80 mg/day defined in study PLX124-01 
(NCT03297424). PLX2853 will be administered once daily + olaparib 600 mg once daily. Note 
that the starting dose of olaparib is fixed and will not be modified. 
Table 5: 
Provisional Dose Escalation Plan for the Combination of PLX2853 + 
Olaparib 
Provisional Dose Escalation Plan 
Dose Level 
PLX2853 Dose 
(mg/day)a 
Olaparib Dose  
(total mg/day)b 
-1 
20 
600  
1 
40 
600  
2 
80 
600  
a 
Once daily (QD) dosing schedule unless otherwise specified. Initial cohort will assess QD dosing. Subsequent 
cohorts may evaluate alternative dosing regimens as agreed to by the Study Committee. 
b 
300 mg twice daily (BID) dosing schedule. 
 
DLTs will be assessed in the first 21-day treatment cycle. In the absence of a DLT and in 
conjunction with review of the safety, PK, and available PD data from each cohort by the Study 
Committee, dose escalation is planned to occur in the following manner: 
• A minimum of 3 to 4 subjects will be initially enrolled in Dose Level 1 (Cohort 1).  
• If a DLT is observed in 1 subject in a given cohort, up to 6 subjects will be treated at that 
dose. 
• If DLTs are observed in 2 or more subjects (or ≥33% of the cohort) at a dose level, the dose 
at which this occurs will be considered intolerable and the MTD to have been exceeded. The 
highest dose level at which 0 or 1 of 6 subjects experience a DLT will be declared the RP2D. 
• If Dose Level 1 is not tolerated, Dose Level -1 (20 mg/day) will be studied. If that dose level 
is intolerable, the study will be halted. 

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• At least 6 subjects must be evaluable at a given dose level in order to be considered an 
RP2D. 
• An RP2D may be declared at a dose level without reaching an MTD if further dose escalation 
is deemed unwarranted. 
• Any subject who misses more than 25% of doses in Cycle 1 (e.g., ≥ 6 doses of PLX2853 in 
21 days) for reasons other than a treatment-related AE, or is withdrawn from the study prior 
to completing Cycle 1 for reasons other than a DLT, will not be DLT evaluable and 
additional subject(s) may be enrolled to provide adequate data for dose escalation decision 
making.  
After dosing has been completed in each cohort, safety, PK data, and PD data (if available) will 
be reviewed, and dose escalation decisions will be made by the Study Committee. Dose 
escalation decisions will also take into consideration safety information beyond the DLT period 
from earlier cohorts. If no DLT is observed, the recommended dose for further evaluation may 
be established based on toxicity, PK, convenience of dosing, and PD (if available) in subjects 
treated at that dose. Dose escalation will only be permitted if adequate safety and tolerability 
have been demonstrated at the previous lower dose for 21 days. Once all ongoing subjects in a 
dose cohort have been treated for at least two 21-day cycles and the safety and tolerability of that 
dose level has been established, intra-subject dose escalation to that dose level may be permitted 
for subjects enrolled at lower dose levels who have not experienced a Grade 3 or higher 
treatment-related toxicity and have completed 2 cycles of PLX2853. Any intra-subject dose 
escalation requires a discussion and agreement with the Medical Monitor. 
5.5 
Concomitant Medications (and Procedures) 
Concomitant treatment is permitted if the medication is not expected to interfere with the 
evaluation of safety or efficacy of the study drug. Other antineoplastic therapy for the treatment 
of the cancer for which subject is enrolled onto this study is not permitted (with the exception of 
certain standard of care hormonal therapies in consultation with the Medical Monitor). During 
the study, if the use of any concomitant treatment becomes necessary (e.g., for treatment or 
prophylaxis of an AE), the treatment must be recorded on the electronic case report form 
(eCRF), including the reason for treatment, generic name of the drug, dosage, route, and date of 
administration. 
Dosing interruptions longer than 2 weeks should generally result in discontinuation from the 
study, unless the subject has demonstrated a clinical benefit (see Section 6.2). Consideration 
should be given to taper prednisone any time a dose hold is required for abiraterone acetate. 
LHRH/GnRH Analogs 
Subjects must have started treatment with an LHRH/GnRH analog at least 28 days prior to first 
dose and must continue treatment while on study or should have had a bilateral orchiectomy. 

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Inhibitors and Inducers of CYP 
Because the rate of metabolism of PLX2853 is very low, CYP2C8 and CYP3A4 inhibitors are 
not expected to have a significant effect on the clearance of PLX2853. However, in the event 
they alter the systemic exposure to PLX2853, strong inhibitors or inducers of CYP3A4 and 
CYP2C8 should be avoided unless necessary and after discussion with the Medical Monitor (see 
Appendix 2 for a list of strong CYP3A4/2C8 inhibitors and inducers). Abiraterone acetate is an 
inhibitor of CYP2C8 and may affect plasma levels of PLX2853. Exposure will be monitored for 
both PLX2853 and abiraterone. 
In addition to the criteria specified above, the following criteria should be followed as 
applicable: 
For subjects receiving abiraterone acetate:  Co-administration with a strong CYP3A4 inducer or 
CYP2D6 substrate with a narrow therapeutic index are prohibited. If an alternative treatment 
cannot be used, PLX2853 and abiraterone acetate must be held until the strong CYP3A4 inducer 
or CYP2D6 substrate with a narrow therapeutic index is discontinued (see Appendix 2). Please 
refer to the ZYTIGA® label or SmPC for additional information. 
For subjects receiving olaparib:  strong and moderate CYP3A inhibitors and inducers should be 
avoided. Co-administration with strong or moderate CYP3A inhibitors should be avoided unless 
necessary. If a CYP3A4 inhibitor cannot be avoided, administration after discussion with the 
Medical Monitor and per the dose modification requirements specified in the label. Please refer 
to the LYNPARZA® label for additional information. 
Antiemetics/Anti-Reflux Medications 
No routine prophylactic anti-emetic treatment is required at the start of study treatment; however, 
subjects should receive appropriate anti-emetic treatment at the first onset of nausea or vomiting 
and as required thereafter, in accordance with local treatment practice guidelines. 
As per international guidance on antiemetic use in cancer subjects, generally, a single-agent 
antiemetic should be considered (NCCN 2020; Roila 2016). 
Proton pump inhibitors and other gastric pH modifiers should be avoided except for locally 
acting antacids, which can be administered 2 hours before or after PLX2853 administration. 
Radiotherapy 
Palliative radiotherapy may be used for the treatment of pain at the site of bony metastases that 
were present at baseline following the completion of Cycle 1, provided the investigator does not 
feel that these are indicative of clinical disease progression during the study period. Study 
treatment should be discontinued for a minimum of 3 days before a subject undergoes 
therapeutic palliative radiation treatment. Study treatment should be restarted within 21 days as 
long as any bone marrow toxicity has recovered. 

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Bisphosphates and Denosumab 
Subjects are permitted to continue treatment with bisphosphonates or denosumab if receiving a 
stable dose at least 4 weeks from starting study treatment. Once on study treatment, initiation of 
new bisphosphonate or denosumab therapy is not permitted, unless approved by the Medical 
Monitor. Dose adjustments may be allowed only after agreement between the Principal 
Investigator and Medical Monitor. 
Anticoagulation Therapy 
Treatment with warfarin is prohibited while on study treatment. In the event initiation of 
treatment with warfarin is clinically required, the subject must be discontinued from the study. 
Biotin and Biotin-Containing Supplements 
The use of biotin (i.e., Vitamin B7) or supplements containing biotin higher than the daily 
adequate intake of 30 µg is prohibited during the study (NIH-ODS 2020). A total daily dose of 
30 µg or less is allowed. 
Concomitant medications known to prolong the QT interval are prohibited while receiving study 
drug (drugs with a low risk of QTc prolongation that are needed for infection control or nausea 
may be permitted with approval from the Medical Monitor). 
All ongoing medications and therapies (including herbal products, nutritional supplements, and 
nontraditional medications) at Screening will be considered prior medications. All medications 
and procedures must be recorded on the appropriate eCRFs at the start of Screening until 30-day 
Follow-up procedures are performed or until the initiation of a non-protocol therapy for the 
underlying malignancy, whichever occurs first. 
5.6 
Precautions and Restrictions 
There are no non-medication-related restrictions or precautions. 
5.7 
Management of Clinical Events 
All necessary support care shall be available to subjects. For dose modification guidelines, see 
Section 6.2. 
5.8 
Blinding and Unblinding 
Blinding methods will not be employed; PLX2853, abiraterone acetate, prednisone, and olaparib 
will be administered in open-label fashion. 

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5.9 
Preparation, Reconstitution, and Dispensation 
PLX2853 is an anti-cancer drug and, as with other potential toxic compounds, caution should be 
exercised when handling PLX2853. Specific instructions on preparation, reconstitution, and 
dispensation will be provided in the Study Pharmacy Manual. 
Refer to the applicable product labels for instructions on preparation, reconstitution, and 
dispensation for abiraterone acetate and prednisone (or equivalent) or olaparib. 
5.10 
Packaging and Labeling 
PLX2853 tablets are manufactured, packaged, and labeled according to Good Manufacturing 
Practice and Good Clinical Practice (GCP) at the following address: 
 
 
BioDuro LLC  
 
 
11011 Torreyana Road #100 
 
 
San Diego, CA 92121 
Abiraterone acetate, prednisone (or equivalent), and olaparib will not be provided by the Sponsor 
and commercially available product should be used. They are packaged per their labels. 
5.11 
Storage, Handling, and Accountability 
PLX2853 tablets, abiraterone acetate tablets, prednisone tablets, and olaparib tablets should be 
stored at room temperature 20°C to 25°C (68°F–77°F); excursions are permitted between 15°C 
and 30°C (59°F and 86°F). Subjects will be requested to store PLX2853, abiraterone acetate, 
prednisone, and/or olaparib at the recommended storage conditions noted on the label. 
The study drugs provided in accordance with this protocol will be kept in a secure place and will 
only be supplied to subjects participating in this study. The Principal Investigator is accountable 
for all study drug supplied by the Sponsor in accordance with this protocol. In addition, the 
Principal Investigator must keep accurate and up-to-date dispensation records. Any study drug 
accidently or deliberately destroyed must be recorded in a timely fashion, including an 
explanation for the destruction in writing. Any discrepancies between the amounts of study drug 
dispensed and returned must also be explained in writing. All such records of drug accountability 
must be entered on the corresponding subject eCRFs. 
All unused and partially used study drug must be sealed and returned to the Sponsor or designee 
or destroyed on site in accordance with the established procedures for drug destruction. Details 
of destruction, including, but not limited to, the number of boxes destroyed, batch number, and 
the date and method of destruction must be recorded on the study drug destruction logs. 
Refer to the Pharmacy Manual for additional details on accountability of all study drug, and 
storage and handling of PLX2853. Refer to the applicable product label for additional details on 
storage and handling of abiraterone acetate, prednisone, and olaparib (or equivalent). 

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5.12 
Other Protocol-specified Materials 
Central laboratory kits will be provided for sample collection, shipment, and storage for PK and 
pharmacodynamic analyses. 

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6.0 
DOSE-LIMITING TOXICITIES AND DOSE MODIFICATIONS 
6.1 
Definitions of Dose-limiting Toxicity 
DLTs are defined as clinically significant AEs or laboratory abnormalities occurring during the 
first cycle (21 days) of study drug administration that are at least possibly related to any study 
drug (PLX2853, abiraterone acetate, olaparib, or prednisone), and that meet one of the following 
CTCAE v5.0 criteria below. DLTs will be evaluated for each cohort. DLTs will be assessed 
during a DLT assessment window of 21 days in Cycle 1. Toxicities occurring in treatment 
Cycle 2 or later will be reviewed and their impact on dose escalation and dosing frequency 
assessed. If during the DLT window a subject requires treatment with a concomitant medication 
that results in a dose reduction of abiraterone acetate or olaparib (per their label), the patient will 
be considered inevaluable, unless the AE requiring treatment meets the definition of a DLT. 
In Phase 1, a subject who misses greater than 25% of their expected doses in Cycle 1, or does not 
complete Cycle 1,for reasons other than a related toxicity will be considered inevaluable and 
may be replaced.  
DLTs will be determined based on the following criteria: 
Hematologic Toxicities 
• Grade 4 neutropenia lasting >5 days 
• Febrile neutropenia 
• Grade 4 thrombocytopenia of any duration 
• Grade ≥3 thrombocytopenia with clinically significant hemorrhage for any duration 
• Grade 4 anemia 
Non-Hematologic Toxicities 
• A dose reduction required during Cycle 1 due to an AE (except as specified above) 
• AE related treatment delays causing a subject to miss at least 25% of their total expected 
doses of any drug in the combination during Cycle 1 
• Any Grade ≥3 non-hematologic toxicity of any duration, except: 
• Grade 3 nausea, vomiting, or diarrhea and Grade 4 vomiting or diarrhea in the absence of 
maximal medical therapy that resolves in 72 hours 
• Grade 3 fatigue lasting <5 days 
• Grade 3 hypertension that can be controlled with medical therapy 
• An increase of indirect (unconjugated) bilirubin indicative of M. Meulengracht/Gilbert’s 
syndrome 

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• Serum lipase and/or serum amylase Grade 3 ≤ 7 consecutive days without clinical signs 
or symptoms of pancreatitis 
• Grade 3 AST/ALT for <5 days 
• Grade 3 neuropathy in subjects with pre-existing Grade 2 neuropathy 
• ALT/AST >3 x ULN with total bilirubin >2 x ULN without another explanation 
(e.g., cholestasis) 
• Any Grade 3 clinically significant electrolyte imbalance confirmed with repeat assessment 
within 24 hours. 
A subject who experiences a DLT may remain in the study and continue receiving PLX2853, 
abiraterone acetate, and prednisone or PLX2853 and olaparib at a lower dose if the Investigator 
deems the potential benefit outweighs the risk and that the subject is not eligible for, and/or 
interested in, an alternative therapy after agreement by the Medical Monitor. If a subject is 
required to permanently discontinue at least one of the study medications for any reason they 
will be discontinued from all study treatment. For patients receiving abiraterone acetate, if 
PLX2853 and abiraterone acetate are withheld, then consideration should be given to tapering 
the dose of prednisone as clinically indicated. 
AEs occurring in treatment Cycle 2 or later will be collected, analyzed, and discussed with the 
Study Committee to help inform the selection of doses for subsequent study cohorts, including 
the option of dose reduction. If cumulative toxicities (e.g., AEs meeting the criteria of a DLT 
occurring in Cycle 2 or later) are observed requiring dose reductions, dose escalation may be 
halted and more subjects may be treated at that or a lower dose level. 
6.2 
Dose Modification Guidelines 
Reduction/interruption of dosing may take place for study drug-related AEs at any time. Table 6 
presents guidelines for dosage modification and re-treatment for PLX2853 -related toxicities. 
These parameters are only a guide and are not intended to supersede the clinical judgment of the 
treating physician. Dose modifications or interruptions of abiraterone acetate, prednisone, or 
olaparib should follow their label, as well as the guidance below. If an AE requiring a dose 
modification of abiraterone acetate, prednisone, or olaparib is also at least possibly related to 
PLX2853, then PLX2853 should also be reduced by 1 dose level. 
If 1 study drug needs to be temporarily held due to an AE, then all drugs should be held until the 
AE resolves per the dose modification guidelines, unless agreed upon by the investigator and 
Medical Monitor. If 1 study drug needs to be permanently discontinued, then all study drugs  
must be permanently discontinued. If abiraterone acetate is held/discontinued, consideration 
should be given to tapering the dose of prednisone as clinically indicated. 
The dose modification/reduction guidelines are for clinically significant toxicities that are at least 
possibly related to PLX2853 administration. Definitions of “clinically significant” and “related” 

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will be made based on the judgment of the Investigator, and the case should be discussed with 
the Medical Monitor as needed. All adjustments should be made in consultation with the Medical 
Monitor. 
If there is a PLX2853 dosing hold within a cycle (e.g., due to toxicity), study drug dosing will 
resume on the next appropriate day. For example, if the subject has a study drug hold for 10 days 
beginning on Cycle 2 Day 8 (day 1 of hold), the subject should resume the schedule of events for 
Cycle 2 Day 18. If study assessments are missed during a hold, those assessments will be noted 
as not done and the next scheduled assessment day procedures will be followed. Every attempt 
should be made to keep to the 21-day cycle. 
Dosing interruptions longer than 2 weeks due to a treatment-related AE should generally result in 
discontinuation from study treatment, unless the subject has demonstrated a clinical benefit from 
therapy and would like to continue dosing with study drug after discussion with the Sponsor and 
approval by the Medical Monitor. 
In Cycle 2 and beyond, dose interruptions for Grade ≤2 non-hematologic toxicity can be 
implemented at the discretion of the treating physician to manage clinically significant toxicities. 
No dose reduction is required if treatment is resumed within 7 days. Discussion with Medical 
Monitor is required for holds lasting longer than 7 days. 
For subjects being treated with abiraterone acetate and prednisone, monitor patients for 
hypertension, hypokalemia, and fluid retention. Control hypertension and correct hypokalemia 
before and during treatment. Closely monitor patients whose underlying medical conditions 
might be compromised by increases in blood pressure, hypokalemia or fluid retention, such as 
those with heart failure, recent myocardial infarction, cardiovascular disease, or ventricular 
arrhythmia. Monitor for symptoms and signs of adrenocortical insufficiency, and consider 
increased dosage of corticosteroids before, during and after stressful situations. Monitor liver 
function and modify, interrupt, or discontinue dosing of abiraterone acetate as clinically 
indicated and per FDA label. 
For subjects being treated with olaparib, if new or worsening pulmonary symptoms 
(e.g., dyspnea, cough and fever) or radiological abnormalities occur in the absence of a clear 
diagnosis, olaparib must be interrupted and further diagnostic workup (including a high 
resolution CT scan) should be performed promptly to assess the source of symptoms and exclude 
pneumonitis. Following investigation, if no evidence of abnormality is observed on CT imaging 
and symptoms resolve, then study treatment can be resumed at the same dose, if deemed 
appropriate by the investigator in consultation with the Medical Monitor. If pneumonitis is 
confirmed, discontinue olaparib and treat the subject appropriately. 

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Table 6: 
Recommended PLX2853 Dose Modifications 
PLX2853-Related 
Toxicities 
Frequency 
When to Hold or Stop 
Dose Adjustments for 
Resumptiona 
Grade 3 or 4 
neutropenia 
1st Appearance 
Interrupt until ANC 
recovers to ≥1 × 109/L; 
growth factor support 
permitted 
If recovered to ANC ≥1 × 109/L in 
≤7 days, resume at same dose. 
If not recovered to ANC ≥1 × 109/L 
after 7 days, reduce dose by 1 dose 
level. 
2nd Appearance 
Interrupt until ANC 
recovers to ≥1 × 109/L; 
growth factor support 
permitted 
If recovered to ANC ≥1 × 109/L in 
≤7 days, reduce dose by 1 dose 
level. 
If not recovered to ANC ≥1 × 109/L 
after 7 days, reduce dose by 2 dose 
levels. 
3rd Appearance 
Discontinue permanently; 
growth factor support 
permitted 
N/A 
Grade 3 or 4 
febrile neutropenia 
1st Appearance 
Interrupt until ANC and 
fever recover; provide 
growth factor support 
If recovered to ANC ≥1 × 109/L and 
T ≤38°C in ≤7days, reduce dose by 
1 dose level. 
If not recovered to ANC ≥1 × 109/L 
after 7 days, discontinue 
permanently. 
2nd Appearance 
Interrupt until ANC and 
fever recover; provide 
growth factor support 
If recovered to ANC ≥1 × 109/L and 
T ≤38°C, reduce dose by an 
additional 1 dose level.  
If not recovered to ANC ≥1 × 109/L 
after 7 days, discontinue 
permanently. 
3rd Appearance 
Discontinue permanently; 
provide growth factor 
support 
N/A 
Grade 3 or 4 
thrombocytopenia 
without bleeding  
1st Appearance 
Interrupt until PLT 
≥75 × 109/L 
If recovered to PLT ≥75 × 109/L 
≤7 days, resume at same dose. 
If not recovered to PLT ≥75 × 109/L 
after 7 days, reduce dose by 1 dose 
level. 
2nd Appearance of G3 or 
1st Appearance of G4 
Interrupt until PLT 
≥75 × 109/L 
If recovered to PLT ≥75 × 109/L in 
≤7 days, reduce dose by 1 dose 
level. 
If not recovered to PLT ≥75 × 109/L 
after 7 days, reduce dose by 2 dose 
levels. 
3rd Appearance of G3 or 
2nd Appearance of G4 
Discontinue permanently 
N/A 

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PLX2853-Related 
Toxicities 
Frequency 
When to Hold or Stop 
Dose Adjustments for 
Resumptiona 
Grade 3 or 4 
thrombocytopenia 
with clinically 
significant bleeding  
1st Appearance 
Discontinue permanently  
N/A 
Grade 3 anemia 
Any Appearance 
If transfusion support 
given:  no dose hold 
required 
N/A 
If no transfusion support 
given:  Interrupt until 
resolved (Grade 0–1 or 
baseline) 
Resume at same dose once 
recovered 
Other Grade 3 
toxicities 
(excluding  
transaminase 
increases, 
electrolyte 
imbalances, 
nausea, vomiting, 
diarrhea, anorexia, 
dehydration, 
fatigue, 
hypertension, and 
anemia) 
1st Appearance 
Interrupt until resolved 
(Grade 0–1 or baseline); 
start symptomatic 
treatment if possible 
Reduce dose by 1 dose level 
2nd Appearance 
Interrupt until resolved 
(Grade 0–1 or baseline); 
start symptomatic 
treatment if possible 
Reduce dose by 1 dose level 
3rd Appearance 
Discontinue permanently; 
start symptomatic 
treatment if possible 
N/A 
Grade 3 electrolyte 
imbalances, 
nausea, vomiting, 
diarrhea, anorexia, 
dehydration, 
fatigue, and 
hypertension 
1st Appearance 
Interrupt until resolved 
(Grade 0–1 or baseline; for 
hypertension only: 
asymptomatic Grade 2 with 
blood pressure 
<140/90 mm Hg is 
acceptable); start 
symptomatic treatment if 
possible 
If recovered ≤5 days, resume at 
same dose. 
If symptoms persist for >5 days 
despite optimum treatment, reduce 
dose by 1 dose level.  
2nd Appearance 
Interrupt until resolved 
(Grade 0–1 or baseline; for 
hypertension only: 
asymptomatic Grade 2 with 
blood pressure 
<140/90 mm Hg is 
acceptable); start 
symptomatic treatment if 
possible 
If recovered ≤5 days, reduce dose by 
1 dose level. 
If symptoms persist for >5 days 
despite optimum treatment, 
discontinue permanently. 
3rd Appearance 
Discontinue permanently; 
start symptomatic 
treatment if possible 
N/A 

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PLX2853-Related 
Toxicities 
Frequency 
When to Hold or Stop 
Dose Adjustments for 
Resumptiona 
Other Grade 4 
toxicities 
(excluding 
transaminase 
increases, 
electrolyte 
imbalances, 
vomiting, and 
diarrhea) 
1st Appearance 
Discontinue permanently; 
start symptomatic 
treatment if possible 
N/A 
Grade 4 electrolyte 
imbalances 
1st Appearance 
Interrupt until resolved 
(Grade 0–1 or baseline); 
start symptomatic 
treatment if possible 
If recovered ≤2 days on optimum 
treatment, reduce dose by 1 dose 
level. 
If symptoms persist for >2 days 
despite optimum treatment, 
discontinue permanently. 
2nd Appearance 
Discontinue permanently; 
start symptomatic 
treatment if possible 
N/A 
Grade 4 vomiting 
and diarrhea 
1st Appearance 
Interrupt until resolved 
(Grade 0–1 or baseline); 
start symptomatic 
treatment if possible 
If recovered ≤5 days on optimum 
treatment, reduce by dose 1 dose 
level. 
If symptoms persist for >5 days 
despite optimum treatment, 
discontinue permanently. 
2nd Appearance 
Discontinue permanently; 
start symptomatic 
treatment if possible 
N/A 
Transaminase 
increases 
• ALT or AST 
>8 × ULN but 
<20 x ULN 
• ALT or AST 
>5 × ULN for more 
than 2 weeks 
• ALT or AST 
>3 × ULN and Total 
bilirubin >2 × ULN or 
INR >1.5 (in absence 
of anticoagulation) 
• ALT or AST 
>3 × ULN with the 
appearance of fatigue, 
nausea, vomiting, right 
upper quadrant pain or 
tenderness, fever, rash, 
and/or eosinophilia 
(>5%) 
Immediately hold dose and 
discuss with Medical 
Monitor. 
Institute close monitoring. 
Any decision to restart 
after transaminases return 
to baseline must be 
discussed with the Medical 
Monitor. 
If clinically indicated, restart at 
reduced dose.  

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PLX2853-Related 
Toxicities 
Frequency 
When to Hold or Stop 
Dose Adjustments for 
Resumptiona 
• Hy’s Law:  AST/ALT 
>3x ULN and total 
bilirubin >2 x ULN 
and ALP <2x ULN 
with no alternative 
etiology for the 
observed injury 
• ALT or AST 
>20 × ULN 
Discontinue permanently 
N/A 
QTcF >500 msec 
or 60 msec increase 
from baseline 
verified on repeat 
ECG 
First appearance  
Interrupt study drug until 
resolved.  
Upon recovery to QTcF ≤500 msec 
(Grade ≤2), restart at a reduced 
dose. 
Permanently discontinue study drug 
if the QTcF interval remains 
>500 msec and increased >60 msec 
from pretreatment values (after 
controlling cardiac risk factors for 
QT prolongation, e.g., electrolyte 
abnormalities, congestive heart 
failure, and bradyarrhythmias).b 
ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; 
ECG = electrocardiogram; INR = International Normalized Ratio; N/A = not applicable; PLT = platelet; 
ULN = upper limit of normal 
a 
See Table 4 for PLX2853 + abiraterone and prednisone dose levels. See Table 5 for PLX2853 + olaparib dose 
levels. 
b 
QTcF :  Only 1 dose reduction is permitted per subject. Prior to and following treatment initiation or after dose 
modification of study drugs for QTcF prolongation, evaluate ECG and electrolytes (including potassium, 
magnesium, and calcium) after 15 days, and monthly thereafter or more often as clinically indicated. 
 

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7.0 
STUDY CONDUCT AND ASSESSMENTS 
7.1 
Study Conduct 
7.1.1 
Study Personnel and Organizations 
The contact information for the Medical Monitor for this study is presented in Table 7. The 
contact information for the central and any additional clinical laboratories, the coordinating 
investigator for each member state/country, and contract research organization (CRO) can be 
found in the Investigational Site File Binder. A full list of investigators is available in the 
Sponsor’s investigator database. 
Table 7: 
Contact Information 
Medical Monitor:  
(Emergency Contacts) 
Jackie Walling, MBChB, PH.D 
Vice President, Clinical Development 
Plexxikon Inc.  
329 Oyster Point Blvd. 
South San Francisco, CA 94080, USA 
Phone:  +1-650-483-9726 
Fax:  +1-510-548-8014 
E-mail:  jwalling@plexxikon.com 
SAE Reporting Contact 
Report all SAEs, whether related or not to study drug, by emailing 
a completed SAE form within 24 hours of receiving knowledge of 
the event to: 
Email:  Plexxikon.Safety@premier-research.com 
Fax:  +1-215-972-8765 
SAE = serious adverse event 
 
7.1.2 
Study Committee 
The Study Committee will include at minimum the Sponsor Medical Monitor and participating 
Principal Investigators. The Study Committee will meet for Phase 1b dose escalation decisions 
and approximately monthly during the Phase 2a dose expansion portions of the study. Data to be 
evaluated may include (but are not limited to):  deaths, SAEs, AEs (including treatment-related 
AEs), reasons for treatment discontinuation or dose modification/ interruption, trends in 
laboratory evaluations, PK, and efficacy. The Study Committee may also review any biomarker 
data if it becomes available. The Study Committee charter will be provided as a separate 
document. 
7.1.3 
Arrangements for Recruitment of Subjects 
Recruitment and enrollment strategies for this study may include recruitment from the 
Investigator’s local practice or referrals from other physicians. If advertisements become part of 

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the recruitment strategy, they will be reviewed by the Institutional Review Board (IRB) and/or 
Independent Ethics Committee (IEC). 
7.1.4 
Treatment Group Assignments 
Subjects will be assigned sequentially to the dose cohort and phase of the study. 
7.1.5 
Withdrawal of Subjects from Drug Treatment and Study, and Subject 
Replacement 
The Plexxikon Medical Monitor will monitor safety data throughout the course of the study. The 
Medical Monitor will review SAEs within timeframes mandated by company procedures and 
will review trends, laboratory data, and AEs at periodic intervals and provide for interim safety 
analyses if appropriate. 
Reasons a subject may discontinue or be withdrawn from the study include, but are not limited 
to, AE, clinically significant disease progression, subject request, investigator decision, protocol 
violation, subject noncompliance, and study termination by the Sponsor or IRB/IEC. When a 
subject discontinues or is withdrawn, the Investigator will notify the Sponsor and should perform 
the procedures indicated in the 30-day FU Visit column in the Schedule of Events approximately 
30 days after discontinuation of study drug or prior to initiation of any new anti-cancer therapy, 
whichever occurs first. Follow-up information may be obtained for subjects who discontinue 
treatment in the study. 
Subjects in Phase 1b who discontinue PLX2853 or abiraterone acetate/prednisone, or olaparib in 
Cycle 1, or miss greater than 25% of their expected doses, for reasons other than toxicity or 
clinically significant disease progression (e.g., protocol violation or noncompliance) during 
Cycle 1 may be replaced at the discretion of the Medical Monitor. Study drug administration 
may be discontinued for an AE or at the discretion of the Investigator. 
Subjects in Phase 2a who do not complete their 9-week disease response assessment for reasons 
other than disease progression may be replaced. 
The consequence of withdrawal of all consent by a subject will be that no new information will 
be collected from that subject and added to the existing data or any database. However, every 
effort will be made to follow all subjects for safety. 
7.1.6 
Study Compliance 
The study drugs PLX2853, abiraterone acetate, prednisone, and olaparib will be provided only to 
eligible subjects under the supervision of the Investigator or identified sub-investigator(s). The 
appropriate study personnel will maintain records of study drug receipt and dispensing. Any 
discrepancy regarding the dose administered and the reason for the discrepancy will be recorded 
in the eCRF. At each clinic visit, subjects will be questioned about their compliance with study 
drug administration, and their dosing diary should be reviewed. 

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7.1.7 
Enrollment of Subjects 
After potential subjects have been identified by the site personnel, the site will inform the 
Sponsor/Sponsor’s representative (and for Phase 1b a slot may be temporarily reserved for the 
subject). Once informed consent has been obtained and all Screening assessments are completed, 
the site personnel will email the Sponsor/Sponsor’s representative with the enrollment packet. 
The Sponsor’s Medical Monitor or designee will review and approve the enrollment (via email 
typically), inform the Investigator that the subject has been approved for enrollment, and assign 
the appropriate dose level, if applicable. A subject will be considered enrolled once they have 
received their first dose of PLX2853. 
Subjects who are approved to enroll (signed enrollment form returned by Plexxikon) but do not 
receive study drug will be considered screen fails. 
Further information may be found in the Investigational Site File Binder. 
7.1.8 
Protocol Deviations 
A protocol deviation is any departure from the protocol. Significant protocol deviations are 
defined as departures from protocol-required processes or procedures that affect subject safety or 
potential benefit or confound assessments of safety or clinical activity. Protocol deviations may 
be grouped into the following categories: 
• Enrollment criteria 
• Study activities (e.g., missed evaluations or visits, data verification issues) 
• Noncompliance with dose or schedule, including dose calculation, administration, 
interruption, reduction, or delay, or discontinuation criteria 
• Use of a prohibited medication 
• AE not reported/SAE reported late 
• Investigational product handling, including storage and accountability 
• Informed consent and ethical issues 
Significant protocol deviations should be reported to the Sponsor immediately upon awareness 
and submitted to the site’s IRB/IEC per institutional policy. 
7.2 
Study Assessments 
All subjects must provide written informed consent. During the consent process, the person 
obtaining consent must inform the subject of all elements of the study. No protocol-specific 
procedures, including Screening procedures, are to be performed until the subject has signed and 
dated an IRB/IEC-approved informed consent form. The study begins with the signing and 
dating of the informed consent form. 

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Screening procedures are to be performed within 28 days of Cycle 1 Day 1 unless otherwise 
specified in the Schedule of Events (Synopsis Table 1 and Synopsis Table 2). 
The 30-day FU Visit will take place approximately 30 days after last dose of PLX2853 or prior 
to starting any new anti-cancer therapy, whichever occurs first (see Section 7.1.5 for reasons for 
discontinuation or withdrawal of a subject from the study). 
Subjects will be followed every 3 months for the first 2 years after the 30-day FU visit and every 
6 months for the third year after the 30-day FU period until death, withdrawal of consent, or loss 
to follow-up. Survival follow-up can be via clinic visit, phone call to the subject or referring 
physician, or other method deemed appropriate by the site, and should assess survival, 
progression, subsequent therapy, and response. 
Subjects who discontinue study treatment without documented disease progression should have 
their disease monitored by radiographic imaging per standard of care until disease progression or 
starting any new anti-cancer therapy, whichever occurs first. Refer to the Schedule of Events 
(Synopsis Table 1 and Synopsis Table 2). 
7.2.1 
Disease Assessment 
Radiographic Assessments will occur every 9 weeks for the first 24 weeks (pre-C4, pre-C7, 
pre-C10) and then every 12 weeks after (pre-C14, pre-C18, etc.), or more frequently as clinically 
indicated. Redacted copies of pathology, molecular pathology, and radiology reports should be 
sent to the Sponsor as part of the enrollment packet and may be requested after each tumor 
response assessment. In addition, redacted copies of radiology scans should be available for an 
independent review if requested by the Sponsor. 
A subject will be considered to have disease progression if one or more of the following occurs: 
• Progression by RECIST v1.1 - increase in measurable lesion size(s) or new lesion 
(Appendix 3) 
• Progression by bone scan per PCWG3 with a confirmatory scan ≥ 6 weeks later 
• PSA progression (defined per PCWG3 as a ≥25% increase and an absolute increase of 
≥2 ng/mL above the nadir, which is confirmed by a second consecutive value obtained 3 or 
more weeks later). PSA progression alone does not necessitate treatment discontinuation. 

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Table 8: 
Radiographic Progression Criteria 
Visit Date 
Criteria for Bone Progression 
Criteria for Soft Tissue Progression 
Week 9 
• 
2 or more new lesions compared to baseline 
bone scan. 
• 
Progressive disease on CT or MRI by 
RECIST v1.1 
• 
Requires confirmation scan at least 6 weeks 
later with > 2 additional lesions compared 
to week 9 scan 
• 
No confirmation scan required. 
Week 18 or 
later 
• 
2 or more new lesions compared to week 9 
bone scan. 
• 
Progressive disease on CT or MRI by 
RECIST v1.1 
• 
Requires confirmation scan at least 6 weeks 
later for persistence or increase in number 
of lesions 
• 
No confirmation scan required. 
 
7.2.1.1 
Soft Tissue Evaluation 
The imaging modalities used for RECIST v1.1 assessment will be CT or MRI scans of the chest, 
abdomen, and pelvis. Any other areas of disease involvement should be additionally investigated 
based on the signs and symptoms of individual subjects. At assessments subsequent to baseline, 
any other sites at which new disease is suspected should also be appropriately imaged. The 
methods of assessment of tumor burden used at baseline must be used at each subsequent 
assessment. Bone lesions will not be included in the RECIST v1.1 soft tissue assessment. 
7.2.1.2 
Bone Metastasis Evaluation 
Bone lesions will be assessed by bone scintigraphy commonly performed with Technetium-99 
(bone scans) based on PCWG3 criteria. Bone lesions will be assessed by bone scan and will not 
be part of the RECIST v1.1 malignant soft tissue assessment. Positive hot spots on the bone scan 
should be considered significant and unequivocal sites of malignant disease to be recorded as 
metastatic bone lesions. 
The first bone scan should be performed 9 weeks after initiating treatment unless clinically 
indicated, as there may be evidence of a flare response early on which may confuse the response 
evaluation. A patient will be considered to have progressed based on the criteria in Table 8. 
7.2.1.3 
PSA Evaluation 
PSA progression is defined as a ≥25% increase and an absolute increase of ≥2 ng/mL above the 
nadir, which is confirmed by a second consecutive value obtained three or more weeks later 
(per PCWG3). Per PCWG3, in the event a subject meets the criteria for PSA progression 
<12 weeks after starting treatment, the subject should continue on treatment until documented 
PSA progression is confirmed ≥12 weeks from start of treatment or there is other evidence of 
disease progression prior to 12 weeks. 

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7.2.1.4 
Symptomatic Skeletal-Related Events (SSRE) 
SSREs will be assessed at each visit during the treatment phase, up to and including the study 
treatment discontinued visit. An SSRE is defined as one or more of the following: 
• Use of radiation therapy to bone in order to prevent or relieve skeletal complications 
• Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral, 
resulting from minimal or no trauma) 
• Occurrence of spinal cord compression 
• A tumor related orthopedic surgical intervention. 
The occurrence of a SSRE alone, in the absence of disease progression, does not necessitate 
treatment discontinuation. 
7.2.2 
Archival Tissue 
Archival tissue samples will be collected at Screening. All subjects will be required to permit 
exploratory evaluations of their archival tumor tissue. If >6 months (approximately) have elapsed 
since the last biopsy, a repeat biopsy of representative lesions (in the judgment of the 
Investigator) is recommended, but not required. When available, tumor samples from soft tissue 
lesions should be submitted instead of tissue from bony metastatic sites. If bony tissue must be 
submitted, it cannot have been decalcified.  
Refer to the Laboratory Manual for specific details on the archival tissue sample requirements.  
7.2.3 
Fresh Tumor Biopsy 
Subjects with biopsy-accessible tumors will be asked to participate in an exploratory evaluation 
of paired biopsies, with samples taken at Screening, Cycle 2 Day 1, and any other time per the 
discretion of the Investigator. If the subject consents to the optional paired biopsies and the 
archival tissue provided was collected within 2 months of Screening, a fresh sample does not 
need to be collected at Screening. The biopsies should be from the same lesion if 
possible/feasible, and preferably from a non-target lesion. 
Further handling/shipping instructions may be found in the Laboratory Manual. 
7.2.4 
Pharmacokinetic and Pharmacodynamic Assessments 
All blood, urine, and tissue samples may be used interchangeably and for multiple types of 
biomarker and PK assays. Because the identification of new biomarkers of disease and treatment 
response is a rapidly developing field, a definitive list of assays remains to be determined. 
Subjects should be instructed not to take their PLX2853 and abiraterone acetate or PLX2853 and 
olaparib dose at home on PK or pharmacodynamics collection days. 

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Stored samples will only have the subject study number as an identifier, and will not have any 
subject identifying information such as name, birthdate, etc. Samples will be stored for 3 years 
after the end of the study (defined as execution of the clinical study report), or per local 
guidelines, and then they will be destroyed. 
In addition to scheduled PK assessments, samples for PK should be collected for any dose 
modification at the time points specified in the Schedule of Events (Synopsis Table 1 and 
Synopsis Table 2) within 2 weeks of the modification or at the next scheduled clinic visit, 
whichever occurs closes to the new dosing regimen. Additional samples for PK may also be 
collected if a subject experiences a DLT, SAE, adverse event of special interest (AESI), or at the 
Sponsor’s request. A list of protocol-required PK and pharmacodynamics assessments is 
provided in Appendix 1. 
A total volume of blood collected in Cycle 1 (21-day cycle) will be approximately 250 mL and 
all subsequent cycles will be no more than approximately 120 mL. Further information may be 
found in the Laboratory Manual. 
7.2.5 
Pharmacokinetic Assessments 
The PK parameters of PLX2853 and abiraterone, or olaparib will be assessed by measuring the 
AUC from time zero to time of last measurable concentration postdose (AUC0-last), AUC from 
time zero to 24 hours postdose (AUC0-24), AUC from time zero extrapolated to infinite time 
(AUC0-∞), Cmax, time to Cmax (Tmax), terminal elimination half-life (T1/2), and accumulation ratio 
at steady state. 
Dose proportionality following study dosing will be explored by analyzing natural 
log -transformed PK variables, AUC0-last, AUC0-24, AUC0-∞, and Cmax, with a linear model 
including the natural log-transformed dose as a covariate. 
7.2.6 
Biomarker Samples and Pharmacogenomics 
Baseline subject blood samples (serum, plasma, whole blood) will be obtained for 
pharmacodynamics and biomarker assessments. These may be repeated at subsequent time points 
throughout the study. In addition, subjects will be asked to submit archival tumor samples, and 
may be asked to have subsequent tumor biopsies while on the study. These tumor samples may 
be used for pharmacodynamics and biomarker assessments. While some of the assessments are 
prospectively described in the protocol, new assessment methods may emerge during the study 
or after it has concluded. Hence some samples may be stored and analyzed at a later date as 
newer technologies emerge. 
Pharmacodynamics and other biomarker samples may be used to identify prognostic or 
predictive biomarkers. In addition, they may be used to improve the understanding of the biology 
of the disease under study, the metabolism of the drug, to help identify subjects who may be 
more or less likely to benefit from the drug, or who may be at risk for potential toxicity from the 
drug. 

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Analyses to be done on the samples (blood and tumor) for this study may include, but are not 
limited to: 
• Gene expression, nucleic acid sequencing, histochemical and/or protein analyses of plasma, 
peripheral blood cells, and/or tumor tissue 
• Analysis of CTC status and possibly other exploratory markers of response or resistance. 
Exploratory analysis of biomarker samples may also be performed to learn about the drug and 
disease properties. 
The science of biomarkers and assays is always evolving and therefore a definitive list of 
biomarkers remains to be determined and may include additional markers suggested by 
preclinical/clinical research or referenced in the literature or other scientific conferences as the 
science and technology evolve. 
As part of this study, blood samples will be collected for pharmacogenomics analysis. Where 
required by local regulations, participation in pharmacogenomic sample collection is optional 
and will be addressed in a separate Pharmacogenomics informed consent form at Screening. In 
these regions, subjects who choose not to provide a sample for pharmacogenetic analysis may 
still participate in the study. 
For subjects who participate in pharmacogenetic testing, a blood sample should be collected at 
the Screening Visit or as indicated in the Schedule of Events. This sample may be analyzed only 
for genes suspected to contribute to the safety and efficacy of the study medications. The 
analysis may also include a comprehensive evaluation of genetic information, with a particular 
focus on specific genetic changes considered to potentially predict responsiveness or resistance 
to treatment. 
Results may also provide information on how individuals metabolize and react to the study drug 
or help to identify subjects who are more or less likely to benefit from the study drugs. The 
information may be useful to increase the knowledge of differences among individuals in the 
way they metabolize the study drug, as well as helping in the development of new drugs or 
improvement of existing drugs. 
Because emerging information regarding the safety and efficacy of study medications may 
become available in the future, pharmacogenomic samples may also be banked for possible 
future research. In all regions, pharmacogenomic sample banking is optional and will be 
addressed in a separate Pharmacogenomics informed consent form at Screening. Samples will be 
retained until the DNA has been exhausted or until the Sponsor instructs the genotyping 
contractor to destroy the sample (in accordance with protocol requirements and laboratory 
procedures). During the period of storage, the DNA sample will not be immortalized or sold to 
anyone. Subjects will have the right to withdraw consent and have their sample destroyed at any 
time. 

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The samples will be shipped to a central laboratory for forwarding to analysis laboratory(ies), 
which has been contracted by the Sponsor to process these samples. Sample collection, 
preparation, handling, storage, and shipping instructions are in the Laboratory Manual. Blood 
volume for blood draws is provided in Section 7.3. 
7.2.7 
Safety Assessments 
Safety and tolerability will be monitored and determined by reported AEs (including deaths, 
other SAEs, and TEAEs), laboratory tests (hematology, clinical chemistry, coagulation, serum 
inflammation marker, and urinalysis), electrocardiogram (ECG), weight, ECOG, and vital signs. 
7.2.7.1 
Medical and Medication History 
Medical history includes clinically significant diseases, ongoing symptoms, surgeries, cancer 
history, and all medications (e.g., prescription drugs, over-the-counter drugs, herbal/homeopathic 
remedies, nutritional supplements) used by the subject within 28 days prior to the Screening 
Visit and history of treatment for the primary diagnosis, including prior systemic, radiation 
treatment, and surgical treatment. Date of last prior cancer treatment must be documented. 
Radiographic studies performed prior to study entry may be collected for review by the 
Investigator. 
7.2.7.2 
ECOG Performance Status Assessment 
An assessment of performance status will be performed using the ECOG Performance Status 
scale of 0 to 5 (Appendix 5). 
7.2.7.3 
Physical Examinations 
The Investigator or qualified designee will conduct physical examinations. A complete physical 
examination will be conducted at Screening and 30-day FU Visit, and a symptom-directed 
physical examination (based on interval history and/or AEs) will be conducted at all other visits. 
7.2.7.4 
Vital Signs 
Vital signs will be recorded and will include measurements of body temperature, heart rate, 
respiratory rate, systolic and diastolic blood pressure. Predose vital signs must be obtained on 
days that PK/pharmacodynamics samples are taken. On non-PK/non-pharmacodynamics days, 
vital signs do not need to be pre-dose and subjects may self-administer PLX2853 at home either 
prior to or after their clinic visit (if applicable). 
7.2.7.5 
Height and Weight 
Height (Screening only) in centimeters and body weight will be measured. 

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7.2.7.6 
Electrocardiogram 
Subjects should rest in the supine or semi recumbent position for at least 5 minutes before each 
12-lead ECG recording is started. The ECGs should be reviewed, signed, and dated by a 
qualified physician (or qualified physician’s assistant or nurse practitioner) and any clinically 
important finding recorded on the appropriate eCRF. The results will include heart rate, PR 
interval, QRS interval, QT interval, and QTcF interval with QTcF calculation. Fridericia’s 
correction is required:  QTcF = (QT)/3√(RR). The Screening ECG will use a QTcF average. 
Triplicate ECGs should be done predose for Screening and predose Cycle 1 Day 1 
(approximately 10 seconds per ECG over a 5-minute period). All other ECGs are single tracings. 
Additional ECGs should be obtained to evaluate AEs as applicable per standard of care. 
7.2.7.7 
Safety Laboratory Assessments 
The Investigator will monitor the safety laboratory test findings. If any laboratory test is 
abnormal during the course of the study, it will be followed at the discretion of the Investigator. 
Abnormalities of laboratory tests will be evaluated by the Investigator and assessed as either 
clinically significant (CS) or not clinically significant (NCS). Abnormal laboratory values 
deemed by the Investigator to be clinically significant and, thus, constitute or are associated with 
an AE, must be reported on the AE form. Abnormal laboratory values that require intervention 
must be reported on the Adverse Event form whether or not deemed clinically significant. 
A complete list of required safety laboratory tests is provided in Appendix 1. Additional details 
for specific tests are provided in the Laboratory Manual. 
7.3 
Blood Collection 
The estimated volumes of blood to be collected at each visit of the study are shown in Table 9 
and Table 10. The quantities of blood are within accepted limits of 10.5 mL/kg or 550 mL 
(whichever is smaller) per NIH and other published guidelines (DF/HCC 2012; NIHCC 2009; 
NS LIJ 2013). 

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Table 9: 
Phase 1b:  Approximate Blood Sample Volumes Collected 
TEST▼ 
Blood Sample Volumes (mL) 
 SCR 
C1 
C2 
C3 
C4+ 
30-day 
FU 
STUDY DAY► D–28 
to D-1 
D1 
D2 
D8 
D15 
D1 
D15 
D1 
D1 
WINDOW (days)► 
 
 
 
± 2 
± 2 
± 3 
± 3 
± 5 
± 5 
± 7 
PG blood sample 
6 
 
 
 
 
 
 
 
 
 
Hematologya 
8 
8 
 
8 
8 
8 
8 
8 
8 
8 
Chemistrya 
8 
8 
 
8 
8 
8 
8 
8 
8 
8 
Coagulation testsa 
8 
8 
 
8 
8 
8 
8 
8 
8 
8 
CRPa 
5 
5 
 
5 
5 
5 
 
5 
5 
5 
CTCsb  
 
20 
 
 
 
 
 
 
20b 
20 
PSA 
10 
10 
 
 
 
10 
 
10 
10 
10 
HIV and Hepatitis 
A/B/C tests 
9 
 
 
 
 
 
 
 
 
 
Pharmacodynamics 
blood samples 
 
48.5 c 
2.5 
 
5 
31 
 
31 
31 
31 
PK blood samples 
 
36 
6 
 
36 
18 
18 
18 
18 
6 
TOTAL VOLUME 
54 
143.5c 
8.5 
29 
70 
88 
42 
88 
88–
108d 
96 
30-day FU = 30-day follow-up visit; CRP = c-reactive protein; CTCs = Circulating Tumor Cells; 
PG = pharmacogenomics; PK = pharmacokinetic; SCR = Screening 
a 
Estimated volume. Actual volume will be per site’s standard of care. 
b 
CTCs assessed (if at least 5 cells/7.5 mL blood detected at baseline) every 9 weeks (± 7 days) for the first 
24 weeks of treatment (pre-C4, pre-C7, pre-C10), then every 12 weeks after (pre-C14, pre-C18, etc.), or more 
frequently as clinically indicated. 
c 
Subjects receiving abiraterone, an extra 10 mL of blood drawn for ARv7 testing on C1D1 (further details are in 
laboratory manual). Subjects receiving olaparib will have an estimated 38.5 mL of PD pharmacodynamics 
blood samples (121.5 mL total) drawn on C1D1. 
d 
Lower range reflects estimated blood collection volume without CTC assessment, upper range reflects 
estimated blood collection volume with CTC assessment. 
 

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8.0 
STATISTICAL AND QUANTITATIVE ANALYSES 
8.1 
Randomization and Stratification 
No randomization or stratification of subjects is planned for this study. 
8.2 
Definitions and Populations for Analysis 
A screened subject is defined as a subject who signed an informed consent form. 
An enrolled subject is defined as a subject who has received at least 1 dose of study drug. 
A screening failure (screen failure) is defined as a subject who signs consent but is not dosed. 
8.2.1 
Evaluable Populations 
The Efficacy Evaluable Population consists of all subjects who received any treatment with 
PLX2853+ abiraterone acetate + prednisone or PLX2853 + olaparib and who have at least 
1 post-baseline target lesion response assessment or discontinued because of clinical progression 
or drug-related toxicity. The Safety Population consists of all subjects who receive any treatment 
with study drug and have any follow-up data. 
8.3 
Procedures for Handling Missing, Unused, and Spurious Data 
All available efficacy and safety data will be included in the data listings and tabulations. No 
imputation of values for missing data will be performed. 
8.4 
General Methodology 
Summary of tabulations will be presented by cohort displaying the number of observations, 
mean, standard deviation, median, minimum, and maximum for continuous variables, and the 
number and percent per category for categorical data. 
8.5 
Baseline Comparisons 
Demographic and baseline characteristics will be summarized by cohort. The last assessment 
performed prior to the first PLX2853 dose will be considered baseline. 
8.6 
Efficacy Analysis 
For all subjects, treatment response will be defined as: 
• Objective response by RECIST v1.1 with a minimum interval for confirmation of CR and PR 
of 4 weeks and/or 
• PSA decline of ≥50% from baseline, confirmed by a second consecutive PSA assessment at 
least 3 weeks later 

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• Conversion of circulating tumor cell count (CTC) to <5 cells/7.5 mL blood nadir confirmed 
by an additional assessment at least 3 weeks later (for subjects with a CTC count of 
≥5 cells/7.5 mL blood at baseline) 
Treatment failure will be defined as: 
• Progression by RECIST v1.1 and/or 
• Progression by bone scan with a confirmatory scan ≥6 weeks later and/or 
• PSA progression per PCWG3 (a ≥25% increase and an absolute increase of ≥2 ng/mL above 
the nadir, occurring at least 12 weeks from start of treatment, and confirmed by a second 
consecutive value obtained at least three weeks later). PSA progression alone does not 
necessitate treatment discontinuation. 
Radiographic progression-free survival (rPFS) is defined by either RECIST v1.1 progression 
and/or progression on bone scan. It will be calculated for each subject as the number of days 
from the first day of treatment to the first occurrence of radiographic progression or death from 
any cause. If no event exists, then rPFS will be censored at the last completed disease assessment 
on study. The rPFS time will always be derived based on scan/assessment dates not visit dates. 
When the Investigator is in doubt as to whether PD has occurred and therefore reassesses the 
subject at a later date, the date of the initial scan should be declared as the date of progression if 
the repeat scans confirm progression. 
Duration of response (DOR) will be calculated for each subject with a response as the time from 
date of first documented, confirmed response (CR or PR) using RECIST v1.1 and PCWG3 until 
date of documented progression or death from any cause. 
Best Overall Response (BOR) per RECIST v1.1 will be calculated for each subject with a 
minimum interval for confirmation of CR and PR of 4 weeks. The minimum interval from 
baseline to stable disease (SD) is 6 weeks. 
Overall survival (OS) will be calculated for each subject as the number of days from the first day 
of treatment (Cycle 1 Day 1) to the date of death from any cause. If a subject is lost to follow-up, 
OS is censored at the date of last contact. 
Time to PSA progression will be calculated as number of days from first date of treatment 
(Cycle 1 Day 1) to the date of initial PSA progression per PCWG3 confirmed at least 3 weeks 
later. 
Duration of PSA response will be calculated for each subject with a PSA response as the time 
from date of first documented, confirmed response (CR or PR) using PCWG3 until date of 
documented progression confirmed at least 3 weeks later, or death from any cause. 
Time to first SSRE defined as one or more of the following: 

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• Use of radiation therapy to prevent or relieve skeletal symptoms. 
• Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral). 
Radiologic documentation is required. 
• Occurrence of spinal cord compression. Radiologic documentation required. 
• Orthopedic surgical intervention for bone metastasis. 
 
8.7 
Safety Analysis 
Safety variables to be assessed will include assessment of AEs, physical examinations, 
laboratory test results (hematology, clinical chemistry, coagulation, serum inflammation 
markers, and urinalysis), electrocardiogram, MUGA/ECHO, weight, and vital signs. 
AE terms recorded on the eCRFs will be mapped to preferred terms using the Medical 
Dictionary for Drug Regulatory Activities (MedDRA®) version 23 or later. All TEAEs will be 
summarized according to the system organ class and preferred term within the organ class. 
TEAEs will be tallied for overall frequency (number and percentage of subjects), worst reported 
severity, and relationship to study drug for each preferred term per subject. SAEs will be 
similarly summarized. Listings of deaths, SAEs, and AEs leading to early termination of study 
treatment or premature withdrawal from study will also be provided. 
Laboratory variables will be examined using mean change in value from baseline to scheduled 
time points. Laboratory values will also be categorized according to their CTCAE v5.0 toxicity 
grade and tabulated by worst on-study toxicity grade. The baseline value of a variable is defined 
as the last value obtained on or before the date and time of the first PLX2853 dose. 
ECG, weight, and vital signs will also be summarized by changes from baseline to scheduled 
time points using descriptive statistics. Changes in QTcF will also be evaluated for the 
proportion of subjects with absolute values >500 msec and change from baseline >60 msec. 
8.8 
Pharmacokinetics, Pharmacodynamics, Biomarkers 
8.8.1 
Pharmacokinetic Analysis 
The PK parameters of PLX2853, abiraterone, and olaparib will be assessed by measuring the 
AUC from time zero to time of last measurable concentration postdose (AUC0-last), AUC from 
time zero to 24 hours postdose (AUC0-24), AUC from time zero extrapolated to infinite time 
(AUC0-∞), Cmax, time to Cmax (Tmax), terminal elimination half-life (T1/2), and accumulation ratio 
at steady state. 
Dose proportionality following study dosing will be explored by analyzing natural 
log -transformed PK variables, AUC0-last, AUC0-24, AUC0-∞, and Cmax, with a linear model 
including the natural log-transformed dose as a covariate. 

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8.8.2 
Pharmacodynamic and Other Biomarker Analysis 
Planned biomarker analyses for pharmacodynamics include, but are not limited to: 
• Gene expression, nucleic acid sequencing, histochemical and/or protein analyses of plasma, 
peripheral blood cells, and/or tumor tissue 
• Analysis of CTC status 
Exploratory analysis of biomarker samples may also be performed to learn about the drug and 
disease properties. 
No formal statistical analysis of pharmacodynamics endpoints will be performed. 
Pharmacodynamics data from each assay will be listed, and the possible relationships between 
clinical response and pharmacodynamics variables will be explored. Any biological activity will 
be described. 
8.9 
Analysis and Sample Size 
8.9.1 
Phase 1b – PLX2853 + Abiraterone Acetate + Prednisone Combination and 
PLX2853 + Olaparib Combination Analysis and Sample Size 
Both the PLX2853 + abiraterone acetate + prednisone combination and the PLX2853 + olaparib 
combination will be evaluated using a standard “3+3” design in order to determine the 
MTD/RP2D of PLX2853 for each combination, taking into consideration safety, PK, and PD 
data (if applicable). 
Data will be tabulated and evaluated by descriptive statistics. Statistical analyses for the primary 
objectives will be descriptive only, with no hypothesis testing. Summary tables will present 
results for each dose cohort. Descriptive statistics will be presented for continuous variables, and 
frequencies and percentages will be presented for categorical and ordinal variables. 
8.9.2 
Phase 2a (Dose Expansion) – PLX2853 + Abiraterone Acetate + Prednisone 
Combination Analysis and Sample Size 
Efficacy of PLX2853 + abiraterone acetate + prednisone will be investigated in a cohort of 
subjects with mCRPC. Phase 2a will enroll up to 19 evaluable subjects using a Simon’s 2-stage 
design in which initially 9 evaluable subjects are enrolled. If 2 or more responders are observed 
in 9 evaluable subjects, another 10 evaluable subjects will be enrolled for a total of 19 subjects. 
If 6 or more responders are observed, the study has 80% power with alpha of 0.05 to reject the 
RR of 15% in favor of the RR of 40%. Recruitment will stop if no more than 1 responder is 
observed after the initial 9 subjects have been accrued. ORR will be summarized along with a 
95% confidence interval (CI). A 2-sided 95% CI will be calculated for the true response rate 
based on the Clopper-Pearson method. 

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Safety and PK data will be tabulated and evaluated by descriptive statistics. Statistical analyses 
for the primary objectives will be descriptive only, with no hypothesis testing. Summary tables 
will present results for each dose cohort. Descriptive statistics will be presented for continuous 
variables, and frequencies and percentages will be presented for categorical and ordinal 
variables. 
8.9.3 
Phase 2a (Dose Expansion) – PLX2853 + Olaparib Combination Analysis and 
Sample Size 
Efficacy of PLX2853 + olaparib will be investigated in a cohort of subjects with mCRPC. Phase 
2a will enroll up to 58 evaluable subjects using a Simon’s 2-stage design in which initially 
28 evaluable subjects are enrolled. If 16 or more responders are observed in 28 evaluable 
subjects, another 30 evaluable subjects will be enrolled for a total of 58 subjects. If 38 or more 
responders are observed, the study has 80% power with alpha of 0.05 to reject the RR of 54% in 
favor of the RR of 70%. Recruitment will stop if no more than 15 responders are observed after 
the initial 28 subjects have been accrued. ORR will be summarized along with a 95% confidence 
interval (CI). A 2-sided 95% CI will be calculated for the true response rate based on the 
Clopper-Pearson method. Safety, PK, and PD data will be tabulated and evaluated by descriptive 
statistics. Statistical analyses for the primary objectives will be descriptive only, with no 
hypothesis testing. Summary tables will present results for each dose cohort. Descriptive 
statistics will be presented for continuous variables, and frequencies and percentages will be 
presented for categorical and ordinal variables. 
8.10 
Interim Analysis 
No formal interim analysis is planned. 

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9.0 
ASSESSMENT OF SAFETY AND ADVERSE EVENTS 
Safety and tolerability will be monitored and determined by serial physical examinations, vital 
signs, hematology and chemistry laboratory studies, and reported AEs (including deaths and 
other SAEs and TEAEs). The Investigator will monitor the laboratory test findings. If any 
laboratory test is abnormal during the course of the study, it will be followed at the discretion of 
the Investigator. Abnormalities of laboratory tests are evaluated by the Investigator and assessed 
as either clinically significant or not clinically significant. Abnormal laboratory values deemed 
by the Investigator to be clinically significant and, thus, constitute or are associated with an AE, 
must be reported on the AE form. Abnormal laboratory values that require intervention must be 
reported on the AE form whether or not deemed clinically significant. 
9.1 
Definitions 
9.1.1 
Adverse Event Definition 
An AE is any untoward medical occurrence in a subject administered a pharmaceutical product, 
which does not necessarily have a causal relationship with the treatment. An AE can be any 
unfavorable and unintended sign (e.g., including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of the study drug, whether or not it is considered to be 
study drug related. This includes any newly occurring event or previous condition that has 
increased in severity or frequency since the administration of study drug. An AE includes, but is 
not limited to, the following: 
• Any clinically significant worsening of a preexisting condition except for events clearly 
consistent with progression of disease under study as described in Section 9.3.2 
• An AE occurring from overdose (i.e., a dose higher than that indicated in the protocol) of a 
study drug, whether accidental or intentional 
• An AE occurring from abuse (e.g., use for nonclinical reasons) of a study drug 
• An AE that has been associated with the discontinuation of the use of a study drug 
Any treatment-emergent abnormal laboratory result which is clinically significant, i.e., meeting 
1 or more of the following conditions, should be recorded as a single diagnosis on the AE page 
in the eCRF: 
• Accompanied by clinical symptoms 
• Leading to a change in study medication (e.g., dose modification, interruption or permanent 
discontinuation) 
• Requiring a change in concomitant therapy (e.g., addition of, interruption of, discontinuation 
of, or any other change in a concomitant medication, therapy or treatment) 
AEs will be graded in severity according to CTCAE v5.0 criteria. 

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9.1.2 
Serious Adverse Event Definition 
An SAE is any AE occurring at any dose and regardless of causality that: 
• Results in death 
• Is life-threatening. Life-threatening means that the subject was at immediate risk of death 
from the reaction as it occurred, i.e., it does not include a reaction which hypothetically 
might have caused death had it occurred in a more severe form. 
• Requires in-subject hospitalization longer than 24 hours or prolongation of existing 
hospitalization (see clarification in the paragraph below on planned hospitalizations). An 
emergency room visit without hospitalization is not considered a hospitalization. 
• Results in persistent or significant disability/incapacity. Disability is defined as a substantial 
disruption of a person’s ability to conduct normal life functions. 
• Is a congenital anomaly/birth defect 
• Is an important medical event. An important medical event is an event that may not result in 
death, be life-threatening, or require hospitalization but may be considered an SAE when, 
based upon appropriate medical judgment, it may jeopardize the subject and may require 
medical or surgical intervention to prevent 1 of the outcomes listed in the definitions for 
SAEs. Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in in-subject hospitalization, or the development of drug dependency or drug abuse. 
Clarification should be made between the terms “serious” and “severe” because they ARE NOT 
synonymous. The term “severe” is often used to describe the intensity (severity) of a specific 
event (as in mild, moderate, or severe myocardial infarction); the event itself, however, may be 
of relatively minor medical significance (such as a severe headache). This is NOT the same as 
“serious,” which is based on subject/event outcome or action criteria described above and are 
usually associated with events that pose a threat to a subject’s life or functioning. A severe AE 
does not necessarily need to be considered serious. For example, persistent nausea of several 
hours’ duration may be considered severe nausea but not an SAE. On the other hand, a stroke 
resulting in only a minor degree of disability may be considered mild but would be defined as an 
SAE based on the above noted criteria. Seriousness (not severity) serves as a guide for defining 
regulatory reporting obligations. 
9.2 
Procedures for Recording and Reporting Adverse Events, Serious Adverse Events, 
and Adverse Events of Special Interest 
All AEs spontaneously reported by the subject and/or in response to an open question from study 
personnel or revealed by observation, physical examination, or other diagnostic procedures will 
be recorded on the appropriate page of the CRF. Any clinically relevant deterioration in 
laboratory assessments or other clinical finding is considered an AE and must be recorded on the 

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appropriate pages of the CRF. When possible, signs and symptoms indicating a common 
underlying pathology should be noted as 1 comprehensive event. 
All SAEs, as defined in Section 9.1.2, and AESIs, as defined in Section 9.3.1, that occur during 
the course of the study as defined in Section 9.3 must be reported within 24 hours of awareness 
by using the SAE Report Form. All SAEs and deaths must be reported whether or not considered 
causally related to the study drug, except for events clearly consistent with progression of disease 
under study as described in Section 9.3.2. SAEs and deaths will be reported by completing the 
SAE Report Form and by emailing (fax as back-up) the completed SAE Report Form to the 
designated recipient (Section 7.1.1). A sample of the SAE Report Form may be found in the 
Study Reference Manual. Follow-up information on the SAE may be requested by Plexxikon. 
SAEs reported to Product Safety must match the data provided on the eCRF. Contact 
information will be listed on the SAE Report Form. 
Planned hospital admissions or surgical procedures for an illness or disease which existed before 
the subject was enrolled in the study or before study drug was given are not to be considered AEs 
unless the condition deteriorated in an unexpected manner during the study (e.g., surgery was 
performed earlier or later than planned). 
For both serious and non-serious AEs, the Investigator must determine both the intensity of the 
event and the relationship of the event to study drug administration. 
Intensity for each AE, including any laboratory abnormality, will be determined by using the 
NCI CTCAE v5.0, as a guideline, wherever possible. The criteria are provided in the Study 
Reference Manual and are also available online at:  http://ctep.cancer.gov/reporting/ctc.html. In 
those cases where the NCI CTC criteria do not apply, intensity should be defined according to 
the following criteria: 
Mild 
Awareness of sign or symptom, but easily tolerated 
Moderate 
Discomfort enough to cause interference with normal daily activities 
Severe 
Inability to perform normal daily activities 
Relatedness to study drug administration will be determined by the Investigator responding to 
the question, ‘Is there a reasonable possibility that the AE is associated with the study drug?’ 
Relatedness to study drug administration will be graded as “probably,” “possibly,” or “not 
related,” as follows: 

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Not  
Related 
Another cause of the event is most plausible; 
OR, 
Clinically plausible temporal sequence is inconsistent with the onset of the 
event and the study treatment administration; 
OR, 
A causal relationship is considered biologically implausible. 
Possibly 
Related  
An event that follows a reasonable temporal sequence from administration 
of the study treatment or a known or expected response pattern to the 
suspected drug, but that could readily have been produced by a number of 
other factors.  
Probably 
Related  
An event that follows a reasonable temporal sequence from administration 
of the study treatment, 
AND, 
There is a biologically plausible mechanism for study treatment causing or 
contributing to the AE, 
AND, 
The event could not be reasonably explained by the known characteristics 
of the subject’s clinical state. 
In addition, the relationship may be confirmed by improvement on stopping the study treatment 
and reappearance of the event on repeated exposure. 
9.3 
Timing of Evaluation of Adverse Events and Serious Adverse Events 
All AEs will be recorded from the time the informed consent is signed through 30 days after last 
dose of study drug or prior to initiating new anti-cancer therapy, whichever occurs first. AEs that 
occur after signing informed consent but before first dose of study drug that are not related to a 
protocol-mandated procedure will be recorded as medical history only. AEs occurring as a result 
of a protocol-mandated procedure after signing of informed consent will be recorded as AEs. 
All SAEs will be recorded from the time the informed consent is signed through 30 days after 
last dose of study or prior to starting any new anti-cancer therapy, whichever occurs first. Any 
SAE occurring from time of consent to initiation of study drug that is related to a 
protocol-mandated procedure must be reported to Plexxikon or its designee within 24 hours of 
the knowledge of the event. SAEs that occur after signing informed consent but before first dose 
of study drug that are not related to a protocol-mandated procedure will be recorded as medical 
history only and do not need to be reported to Plexxikon or its designee within 24 hours of the 
knowledge of the event. All SAEs occurring from start of study drug through 30 days after 
administration of the last dose of study drug or prior to the administration of any new anti-cancer 
therapy, whichever occurs first, must be reported to Plexxikon or its designee within 24 hours of 
the knowledge of the event. 

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9.3.1 
Adverse Events of Special Interest 
At present, there are no adverse events of special interest for PLX2853. 
At present, adverse events of special interest for olaparib include:  any event of MDS/AML, new 
primary malignancy, or pneumonitis should be reported to the Sponsor whether it is considered a 
non-serious AE (e.g., non-melanoma skin cancer) or SAE, and regardless of investigator’s 
assessment of causality or knowledge of the treatment arm. 
AESIs will be reported per Section 9.2. 
9.3.2 
Worsening of Cancer 
Clear progression of neoplasia should not be reported as an AE or SAE. Findings that are clearly 
consistent with the expected progression of the underlying cancer should not be reported as an 
AE, and hospitalizations due to the progression of cancer do not qualify for an SAE. Sudden and 
unexplained death should be reported as an SAE. If there is any uncertainty about a finding being 
due solely to progression of neoplasia, the finding should be reported as an AE or SAE as 
appropriate. 
9.3.3 
Overdose 
Certain information, although not considered an AE, must be recorded in the eCRF and followed 
up as indicated for an AE. This may include the following: 
• Overdose 
• Study drug overdose is the accidental or intentional use of PLX2853, abiraterone acetate, 
prednisone, or olaparib in an amount at least 40% higher than the prescribed dose on any 
given day. An overdose or incorrect administration of study drug is not an AE unless it 
results in untoward medical effects. Any study drug overdose or incorrect administration 
of study drug should be noted on the appropriate CRF. 
• All AEs associated with an overdose or incorrect administration of study drug should be 
recorded on the adverse event CRF. If the AE also fulfills serious criteria, it should be 
reported as an SAE using the SAE Report Form. 
 
9.4 
Monitoring of Adverse Events and Period of Observation 
AEs, both serious and non-serious, and deaths will be recorded on the CRFs up to and including 
the last visit at approximately 30 days after administration of the last dose of study drug or prior 
to the administration of any new anti-cancer therapy, whichever occurs first. 
Any SAE that occurs at any time after completion of the study and the designated follow-up 
period, which the Investigator considers to be related to study drug, must be reported to 
Plexxikon or designee. 

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All SAEs must be followed by the Investigator until one of the following occurs: 
• The event resolves 
• The event stabilizes 
• The event returns to baseline, if a baseline value/status is available 
• The event can be attributed to etiology other than the study drug or to factors unrelated to 
study conduct 
• 
It becomes unlikely that any additional information can be obtained (subject or health care 
practitioner refusal to provide additional information, lost to follow-up after demonstration of 
due diligence with follow-up efforts). 
 
9.5 
Procedures for Reporting Drug Exposure During Pregnancy and Birth Events 
If the female partner of a study subject becomes pregnant or suspects she is pregnant while the 
subject is participating in this study or up to 90 days after completing study treatment, he must 
inform his treating physician immediately. The Sponsor must also be contacted immediately by 
emailing or faxing a completed Pregnancy Form to Plexxikon or designee as described in the 
Study Reference Manual. The pregnancy must be followed through final outcome (i.e., beyond 
delivery) for SAEs. 

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10.0 
ADMINISTRATIVE REQUIREMENTS 
10.1 
Good Clinical Practice 
The study will be conducted in accordance with the ICH Guideline for GCP and the appropriate 
regulatory requirement(s). The Investigator will be thoroughly familiar with the appropriate use 
of the study drug as described in the protocol and the Investigator’s Brochure. 
10.2 
Data Quality Assurance 
The Investigator is required to prepare and maintain adequate and accurate case histories 
designed to record all observations and other data pertinent to the study for each study subject. 
Study data will be entered into an eCRF by site personnel using a secure, validated web-based 
EDC application. Plexxikon and its CRO designee will have access to all data upon entry in the 
EDC application. 
Study monitors will discuss instances of missing or un-interpretable data with the Investigator 
for resolution. Any changes to study data will be made to the eCRF and documented via an 
electronic audit trail associated with the affected eCRF. 
10.3 
Electronic Case Report Form Completion 
Plexxikon or a CRO designee will provide the study sites with secure access to and training on 
the EDC application, sufficient to permit site personnel to enter or correct information in the 
eCRFs for the subjects for which they are responsible. 
eCRFs will be completed for each study subject. Screen failure information will not be collected 
in the eCRFs. It is the Investigator’s responsibility to ensure the accuracy, completeness, clarity, 
and timeliness of the data reported in the subject’s eCRF. 
The Investigator, or designated representative, should complete the eCRF as soon as possible 
after information is collected. 
The audit trail entry will show the user’s identification information, and the date and time of the 
correction. The Investigator must provide through the EDC application formal approval of all the 
information in the eCRFs and changes to the eCRFs to endorse the final submitted data for the 
subjects for which he is responsible. 
Plexxikon or a CRO designee will retain the eCRF data and corresponding audit trails. A copy of 
the final archival eCRF in the form of a compact disk or other electronic media will be placed in 
the Investigator’s study file. 
10.4 
Study Monitoring 
Monitoring and auditing procedures developed or approved by Plexxikon will be followed, in 
order to comply with GCP guidelines. 

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All information recorded on the eCRFs for this study must be consistent with the subject’s 
source documentation. During the course of the study, the study monitor will make study site 
visits to review protocol compliance, verify eCRFs against source documentation, assess drug 
accountability, and ensure that the study is being conducted according to pertinent regulatory 
requirements. The review of medical records will be performed in a manner to ensure that 
subject confidentiality is maintained. 
10.5 
Ethical Considerations 
The study will be conducted in accordance with ethical principles founded in the Declaration of 
Helsinki. The study must fully adhere to the principles outlined in Guideline for Good Clinical 
Practice E6 (R2), November 2016, or with local law if it affords greater protection for the 
subject. The IRB/IEC will review all appropriate study documentation in order to safeguard the 
rights, safety, and well-being of the subjects. The study will only be conducted at sites where 
IRB/IEC approval has been obtained. The protocol, IB, informed consent form, advertisements 
(if applicable), written information given to the subjects (including diary cards), safety updates, 
annual progress reports, and any revisions to these documents will be provided to the IRB/IEC 
by the Investigator or the Sponsor, as allowable by local regulations. 
10.6 
Subject Information and Informed Consent 
After the study has been fully explained, written informed consent will be obtained from either 
the subject or his/her guardian or legal representative prior to study participation. The method of 
obtaining and documenting the informed consent and the contents of the consent is to comply 
with ICH GCP and all applicable regulatory requirement(s). 
10.7 
Subject Confidentiality 
In order to maintain subject privacy, all eCRFs, study drug accountability records, study reports 
and communications will identify the subject by initials where permitted and/or by the assigned 
subject number. The subject’s confidentiality will be maintained in accordance with applicable 
laws and regulations. 
10.8 
Investigator Compliance 
The Investigator will conduct the study in compliance with the protocol provided by Plexxikon 
and given approval/favorable opinion by the IRB/IEC and the appropriate regulatory 
authority(ies). Modifications to the protocol are not to be made without agreement of both the 
Investigator and Plexxikon. Changes to the protocol will require written IRB/IEC 
approval/favorable opinion prior to implementation, except when the modification is needed to 
eliminate an immediate hazard(s) to subjects. Plexxikon, or a CRO designee, will submit all 
protocol modifications to the appropriate regulatory authority(ies) in accordance with the 
governing regulations. 

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When immediate deviation from the protocol is required to eliminate an immediate hazard(s) to 
subjects, the Investigator will contact Plexxikon, or a CRO designee, if circumstances permit, to 
discuss the planned course of action. Any departures from the protocol must be documented. 
10.9 
On-site Audits 
Regulatory authorities, the IEC/IRB, and/or Plexxikon may request access to all source 
documents, eCRFs, and other study documentation for on-site audit or inspection. Direct access 
to these documents must be guaranteed by the Investigator, who must provide support at all 
times for these activities. 
10.10 Investigator and Site Responsibility for Drug Accountability 
Accountability for the study drug at the study site is the responsibility of the Investigator. Drug 
accountability records indicating the drug’s delivery date to the site, inventory at the site, use by 
each subject, and amount returned to Plexxikon, or a CRO designee, (or disposal of the drug, if 
approved by Plexxikon) will be maintained by the clinical site. Plexxikon or its CRO designee 
will review drug accountability at the site on an ongoing basis. 
All material containing study drug will be treated and disposed of as hazardous waste in 
accordance with governing regulations. 
10.11 Product Complaints 
A product complaint is any dissatisfaction with a product which may be attributed to the identity, 
quality, durability, reliability, or safety of the product. Individuals who identify a potential 
product complaint situation should immediately report the event. Whenever possible, the 
associated product should be maintained in accordance with the label instructions pending 
further guidance from a Plexxikon quality representative. 
For Product Complaints, refer to the Study Pharmacy Manual for instructions and details. 
10.12 Closure of the Study 
The Sponsor currently has no plans to provide PLX2853 to study subjects after the close of the 
study or earlier subject withdrawal. However, the Sponsor will evaluate the appropriateness of 
continuing to provide PLX2853 to study subjects after evaluating study data pertaining to the 
primary efficacy outcome measure and safety. These analyses may be conducted prior to study 
completion. For subjects who are demonstrating a clinical benefit at the end of this study, the 
possibility of continuing their treatment in this or a roll-over protocol may be considered. Within 
90 days of study closure, the Sponsor will notify the competent authorities and the IECs in all 
member states where the study is being carried out that the study has ended. 
Within 1 year of the end of the study, a summary of the clinical study results will be submitted to 
the competent authorities and IECs in all member states involved in the study. 

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Study participation by individual sites may be prematurely terminated if in the opinion of the 
Investigator there is sufficient reasonable cause. Study participation by individual sites or the 
entire study may be prematurely terminated, if in the opinion of the Plexxikon, there is sufficient 
reasonable cause. Written notification documenting the reason for study termination will be 
provided to the Investigator or Plexxikon by the terminating party. 
Circumstances that may warrant termination include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to subjects 
• Failure to enter subjects at an acceptable rate 
• Insufficient adherence to protocol requirements 
• Insufficient, incomplete, and/or un-evaluable data 
• Determination of lack of efficacy 
• Plans to modify, suspend or discontinue the development of the study drug 
Should the study be closed prematurely, the site will no longer be able to access the EDC 
application, will not have a right to use the EDC application, and will cease using the password 
or access materials once their participation in the study has concluded. In the event that any 
access devices for the EDC application have been provided, these will be returned to Plexxikon 
once the site’s participation in the study has concluded. 
Within 15 days of premature closure, Plexxikon must notify the competent authorities and IECs 
of any member state where the study is being conducted, providing the reasons for study closure. 
10.13 Record Retention 
The Investigator will maintain all study records according to ICH GCP and applicable regulatory 
requirement(s). Records will be retained for at least 2 years after the last marketing application 
approval or 2 years after formal discontinuation of the clinical development of the investigational 
product or according to applicable regulatory requirement(s). If the Investigator withdraws from 
the responsibility of keeping the study records, custody must be transferred to a person willing to 
accept the responsibility and Plexxikon notified. 
10.14 Publication and Use of Information 
All information regarding PLX2853 supplied by Plexxikon to the Investigator is privileged and 
confidential information. The Investigator agrees to use this information to accomplish the study 
and will not use it for other purposes without consent from Plexxikon. It is understood that there 
is an obligation to provide Plexxikon with complete data obtained during the study. The 
information obtained from the clinical study will be used towards the development of PLX2853 
and may be disclosed to regulatory authority(ies), other investigators, corporate partners, or 
consultants as required. 

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Upon completion of the clinical study and evaluation of results by Plexxikon, the hospital or 
institution and/or Investigator may publish or disclose the clinical study results pursuant to the 
terms contained in the applicable Clinical Trial Agreement. 

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11.0 
REFERENCES 
Alekseyenko AA, Walsh EM, Wang X, Grayson AR, Hsi PT, Kharchenko PV, et al. The 
oncogenic BRD4–NUT chromatin regulator drives aberrant transcription within large topological 
domains. Genes Dev. 2015;29(14):1507–1523. 
Ambrosini G, Sawle A, Musi E, Schwartz GK. BRD4-targeted therapy induces Myc-independent 
cytotoxicity in Gnaq/11-mutatant uveal melanoma cells. Oncotarget. 2011;6(32):33397–33409. 
Asangani IA, Dommeti VL, Wang X, Malik R, Cieslik M, Yang R, et al. Therapeutic targeting 
of BET bromodomain proteins in castration–resistant prostate cancer. Nature. 
2014;510(7504):278–282. 
Bandopadhayay P, Bergthold G, Nguyen B, Schubert S, Gholamin S, Tang Y, et al. BET 
bromodomain inhibition of MYC–amplified medulloblastoma. Clin Cancer Res. 
2014;20(4):912–925. 
Boi M, Gaudio E, Bonetti P, Kwee I, Bernasconi E, Tarantelli C, et al. The BET bromodomain 
inhibitor OTX015 affects pathogenetic pathways in preclinical B-cell tumor models and 
synergizes with targeted drugs. Clin Cancer Res. 2015;21(7):1628–1638. 
Biotin Health Sheet for Professionals. National Institutes of Health, Office of Dietary 
Supplements, 2020. https://ods.od.nih.gov/factsheets/Biotin-HealthProfessional/ 
Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, et al. Molecular determinants of 
resistance to antiandrogen therapy. Nat Med. 2004;10(1):33–39. 
Cheng Z, Gong Y, Ma Y, Lu K, Lu X, Pierce LA, et al. Inhibition of BET bromodomain targets 
genetically diverse glioblastoma. Clin. Cancer Res. 2013;19(7):1748–1759. 
Cho H, Herzka T, Zheng W, Qi J, Wilkinson JE, Bradner JE, et al. RapidCaP, a novel GEM 
model for metastatic prostate cancer analysis and therapy, reveals myc as a driver of Pten-mutant 
metastasis. Cancer Discov. 2014;4(3):318–333. 
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 
1976;16(1):31–41. 
Coleman DJ, Gao L, King CJ, Schwartzman J, Urrutia J, Sehrawat A, et al. BET bromodomain 
inhibition blocks the function of a critical AR-independent master regulator network in lethal 
prostate cancer. Oncogene. 2019;38(28):5658–5669. 
CredibleMeds®. OncoSupport™, List of medications often used to treat patients with cancer and 
currently listed in one of CredibleMed’s three TdP risk categories. 
https://crediblemeds.org/oncosupport. Accessed 16 February 2020. 

PLX2853 
Protocol PLX124-04 Amendment 3, 29 Oct 2021 
CONFIDENTIAL/PROPRIETARY 
Page 116 of 148 
Plexxikon Inc. 
Dana-Farber/Harvard Cancer Center (DF/HCC). Guidance on Maximum Blood Draw for 
Research Purposes. 22 June 2012. 
Dawson MA, Prinjha RK, Dittmann A, Giotopoulos G, Bantscheff M, Chan WI, et al. Inhibition 
of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature. 
2011;478(7370):529–533. 
de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased 
survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995–2005. 
Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, et al. BET bromodomain 
inhibition as a therapeutic strategy to target c-Myc. Cell. 2011;146(6):904–917. 
Durand F, Valla D. Assessment of the prognosis of cirrhosis:  Child-Pugh versus MELD. 
J Hepatol. 2005;42 Suppl(1):S100–S107. 
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response 
evaluation criteria in solid tumours:  revised RECIST guideline (version 1.1). Eur J Cancer. 
2009;45(2):228–247. 
Faivre EJ, Wilcox D, Lin X, Hessler P, Torrent M, He W, et al. Exploitation of castration-
resistant prostate cancer transcription factor dependencies by the novel BET inhibitor 
ABBV-075. Mol Cancer Res. 2017;15(1):35–44. 
Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, et al. Selective inhibition of 
BET bromodomains. Nature. 2010;468(7327):1067–1073. 
Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, et al. 
Histone recognition and large-scale structural analysis of the human bromodomain family. Cell. 
2012;149(1):214–231. 
French CA. NUT midline carcinoma. Cancer Genet Cytogenet. 2010;203(1):16–20. 
Grasso CS, Wu YM, Robinson DR, Cao X, Dhanasekaran SM, Khan AP, et al. The mutational 
landscape of lethal castration-resistant prostate cancer. Nature. 2012;487(7406):239–243. 
Harris WP, Mostaghel EA, Nelson PS, Montgomery B. Androgen deprivation therapy:  progress 
in understanding mechanisms of resistance and optimizing androgen depletion. Nat Clin Pract 
Urol. 2009; 6(2):76–85. 
Heinemann A, Cullinane C, De Paoli-Iseppi R, Wilmott JS, Gunatilake D, Madore J, et al. 
Combining BET and HDAC inhibitors synergistically induces apoptosis of melanoma and 
suppresses AKT and YAP signaling. Oncotarget. 2015;6(25):21507–21521. 

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Henssen A, Thor T, Odersky A, Heukamp L, El-Hindy N, Beckers A, et al. BET bromodomain 
protein inhibition is a therapeutic option for medulloblastoma. Oncotarget.  
2013;4(11):2080–2095. 
Khalaf D, Annala M, Finch DL, Oja CD, Virgidis J, Zulfiqar M, et al. Phase 2 randomized cross-
over trial of abiraterone + prednisone (ABI+P) vs enzalutamide (ENZ) for patients (pts) with 
metastatic castration resistant prostate cancer (mCRPC):  Results for 2nd-line therapy. Abstract. 
J Clin Oncol. 2018;6(15_suppl):5015. 
Lenhart R, Kirov S, Desilva H, Cao J, Lei M, Johnston K, et al. Sensitivity of small cell lung 
cancer to BET inhibition is mediated by regulation of ASCL1 gene expression. Mol Cancer Ther. 
2015;14(10):2167–2174. 
Lockwood WW, Zejnullahu K, Bradner JE, Varmus H. Sensitivity of human lung 
adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins. Proc Natl 
Acad Sci USA. 2012;109(47):19408–19413. 
LYNPARZA® Full Prescribing Information, 2020, AstraZeneca Pharmaceuticals, LP, 
Wilmington, Delaware, 19850, U.S.A. http://www.janssenlabels.com/package-insert/product-
monograph/prescribing-information/ZYTIGA-pi.pdf 
Mirguet O, Gosmini R, Toum J, Clément CA, Barnathan M, Brusq JM, et al. Discovery of 
epigenetic regulator I-BET762:  lead optimization to afford a clinical candidate inhibitor of the 
BET bromodomains. J Med Chem. 2013;56(19):7501–7515. 
Mukherji D, Eichholz A, De Bono JS. Management of metastatic castration-resistant prostate 
cancer:  recent advances. Drugs. 2012;72(8):1011–1028. 
Muller S, Filippakopoulos P, Knapp S. Bromodomains as therapeutic targets. Expert Rev Mol 
Med. 2011;13:e29. 
National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in 
Oncology (NCCN Guidelines):  Antiemesis, version 2.2020. NCCN.org. 23 Apr 2020. 
National Institutes of Health Clinical Center (NIHCC). Policy and Communication Bulletin:  
Guidelines for Limits of Blood Drawn for Research Purposes in the Clinical Center. 
05 June 2009. 
National Institutes of Health Office of Dietary Supplements (NIH-ODS). Biotin Fact Sheet for 
Health Professionals. https://ods.od.nih.gov/factsheets/Biotin-HealthProfessional. 
19 February 2020. 
Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S, Chung CW, et al. Suppression of 
inflammation by a synthetic histone mimic. Nature. 2010;468(7327):1119–1123. 

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Shimamura T, Chen Z, Soucheray M, Carretero J, Kikuchi E, Tchaicha JH, et al. Efficacy of 
BET bromodomain inhibition in Kras–mutant non–small cell lung cancer. Clin Cancer Res. 
2013;19(22):6183–6192. 
Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. 
Stein M, Goodin S, Dipaola R. Abiraterone in prostate cancer:  a new angle to an old problem. 
Clin Cancer Res. 2012;18(7):1848–1854. 
Stuhlmiller TJ, Miller SM, Zawistowski JS, Nakamura K, Beltran AS, Duncan JS, et al. 
Inhibition of lapatinib-induced kinome reprogramming in ERBB2-positive breast cancer by 
targeting BET family bromodomains. Cell Rep. 2015;11(3):390–404. 
Sun S, Sprenger CC, Vessella RL, Haugk K, Soriano K, Mostaghel EA, et al. Castration 
resistance in human prostate cancer is conferred by a frequently occurring androgen receptor 
splice variant. J Clin Invest. 2010;120(8):2715–2730. 
Taplin ME, Bubley GJ, Ko YJ, Small EJ, Upton M, Rajeshkumar B, et al. Selection for androgen 
receptor mutations in prostate cancers treated with androgen antagonist. Cancer Res. 
1999;59(11):2511–2525. 
Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, et al. Integrative genomic 
profiling of human prostate cancer. Cancer Cell. 2010;18(1):11–22. 
Vázquez R, Civenni G, Kokanovic A, Shinde D, Cantergiani J, Marchetti M, et al. Efficacy of 
novel bromodomain and extraterminal inhibitors in combination with chemotherapy for 
castration-resistant prostate cancer. Eur Urol Oncol. 2019. doi:  10.1016/j.euo.2019.07.013 
Online ahead of print. 
Visakorpi T, Hyytinen E, Koivisto P, Tanner M, Keinänen R, Palmberg C, et al. In vivo 
amplification of the androgen receptor gene and progression of human prostate cancer. 
Nat Genet. 1995;9(4):401–406. 
Welti J, Sharp A, Yuan W, Dolling D, Nava Rodrigues D, Figueiredo I, et al. Targeting 
bromodomain and extra-terminal (BET) family proteins in castration-resistant prostate cancer 
(CRPC). Clin Cancer Res. 2018;24(13):3149–3162. 
Wyce A, Ganji G, Smitheman KN, Chung CW, Korenchuk S, Bai Y, et al. BET inhibition 
silences expression of MYCN and BCL2 and induces cytotoxicity in neuroblastoma tumor 
models. PLoS One. 2013;8(8):e72967. 
Zhu H, Bengsch F, Svoronos N, Rutkowski MR, Bitler BG, Allegrezza MJ, et al. BET 
bromodomain inhibition promotes anti-tumor immunity by suppressing PD-L1 expression. Cell 
Rep. 2016;16(11):2829–2837. 

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Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA, et al. RNAi screen identifies 
Brd4 as a therapeutic target in acute myeloid leukaemia. Nature. 2011;478(7370):524–528. 
ZYTIGA® Full Prescribing Information, 2019. Janssen Biotech, Inc. Horsham, Pennsylvania, 
19044, U.S.A. http://www.janssenlabels.com/package-insert/product-monograph/prescribing-
information/ZYTIGA-pi.pdf 

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APPENDIX 1: 
LABORATORY TESTS 
Hematology 
• Hemoglobin and hematocrit 
• White blood cell (WBC) count with differential (absolute) 
• Platelet count 
Blood Chemistry 
• Sodium 
• Potassium 
• Chloride 
• CO2 
• Calcium 
• Phosphorus 
• Amylase 
• Lipase 
• Magnesium 
• Glucose 
• Blood urea nitrogen 
• Creatininea 
• Uric acid 
• Albumin 
• Total protein 
• Testosterone 
• Total bilirubin 
• Direct bilirubin 
• Aspartate aminotransferase (AST) 
• Alanine aminotransferase (ALT) 
• Alkaline phosphatase (AP) 
• Lactate dehydrogenase (LDH) 
• Gamma-glutamyl transferase (GGT) 
• Hemoglobin A1c (Hgb A1c) 
a 
Creatinine clearance (CrCL) will be collected at all timepoints creatinine is assessed. CrCL can be measured or 
calculated per Cockcroft-Gault (Cockcroft 1976) [age in years, weight (wt) in kilograms]: 
For serum creatinine concentration in mg/dL: 
CrCl = (140 - age) × (wt) / 72× serum creatinine (mg/dL) 
For serum creatinine concentration in μmol/L: 
CrCl = (140 - age) × (wt) / 0.81 × serum creatinine (μmol/L). 
Coagulation Tests 
• Prothrombin time (PT)/International normalized ratio (INR) 
• Activated partial thromboplastin time (aPTT) 
• Fibrinogen 
• D-dimer 
• Factor VII 
Serum Inflammation Marker 
• C-reactive protein 

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Urinalysis (microscopic) 
• pH 
• Protein/albumin 
• Glucose/sugar 
• WBCs 
• Nitrites 
• Ketones/acetone 
• Hemoglobin/blood 
• Casts or other microscopic findings 
Viral Serology Tests 
• Hepatitis A virus immunoglobulin M 
• Hepatitis B virus surface antigen 
• Hepatitis C antibody (if positive, confirmed by HCV ribonucleic acid) 
• HIV 
Blood Tumor Response Assessment 
• Prostate-specific antigen (PSA) 
• Circulating Tumor Cells (CTC) per CELLSEARCH System 
Plasma Samples for PK 
• Area under the plasma concentration-time curve (AUC0-last, AUC0-24, AUC0-∞) 
• Maximum observed concentration (Cmax) 
• Time to maximum observed concentration (Tmax) 
• Terminal elimination half-life (T1/2) 
Blood Biomarkers and Pharmacodynamics 
• Gene expression, nucleic acid sequencing, histochemical and/or protein analyses of plasma, 
peripheral blood cells 
• Analysis of CTC status 
Exploratory analysis of biomarker samples may also be performed to learn about the drug and 
disease properties. 

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Paired Biopsy Tissue Response Biomarkers 
• c-Myc and androgen receptors 
• DNA or RNA sequencing 
• Gene expression 
• Other response or resistance biomarkers as appropriate 
Because the identification of new response prediction or early response biomarkers of disease 
activity is a rapidly developing field, the definitive list of analyses remains to be determined, and 
may include additional markers of macrophage activity, in addition to antitumor biomarkers that 
may be related to PLX2853 treatment. 

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APPENDIX 2: 
STRONG CYP3A4 AND/OR CYP2C8 INHIBITORS AND 
INDUCERS AND CYP2D6 SUBSTRATES WITH A NARROW 
THERAPEUTIC INDEX 
CYP3A4 and/or CYP2C8 Strong Inhibitors 
CYP3A4 and/or CYP2C8 Strong Inducers 
• Protease inhibitors 
 
- Ritonavir 
 
- Indinavir 
 
- Nelfinavir 
 
• Macrolide antibiotics 
 
- Erythromycin 
 
- Telithromycin 
 
- Clarithromycin 
 
• Azole antifungals 
 
- Voriconazole 
 
- Ketoconazole 
 
- Itraconazole 
 
• Chloramphenicol (antibiotic) 
• Nefazodone (antidepressant) 
• Bergamottin (constituent of grapefruit juice) 
• Aprepitant (antiemetic) 
• Verapamil (calcium channel blocker) 
• Gemfibrozil (hypolipidemic) 
• Thiazolidinedione (antidiabetic) 
• Montelukast (Leukotriene receptor 
antagonist) 
• Quercetin (anti-inflammatory) 
• Anticonvulsants, mood stabilizers 
 
- Phenytoin 
 
- Carbamazepine 
 
- Oxcarbazepine 
 
• Non-nucleoside reverse transcriptase 
inhibitors 
 
- Efavirenz 
 
- Nevirapine 
 
- Etravirine 
 
• Phenobarbital (barbiturate) 
• Rifampicin (bactericidal) 
• Modafinil (stimulant) 
• Hyperforin (constituent of St John’s 
Wort) 
• Cyproterone (antiandrogen, progestin) 
 
CYP2D6 Substrates 
• Amiodarone 
• Dosulepin 
• Flecainide 
• Sotalol 
• Pimozide 
• Procainamide 
• Theophylline 
 
This list is not comprehensive and subject to change and all medications should be reviewed 
prior to administering. 

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APPENDIX 3: 
RECIST CRITERIA VERSION 1.1 
From:  Eisenhauer 2009 
Measurability of Tumor at Baseline 
Definitions 
At baseline, tumor lesions/lymph nodes will be categorized measurable or non-measurable as 
follows. 
Measurable tumor lesions 
Tumor lesions must be accurately measured in at least 1 dimension (longest diameter in the plane 
of measurement is to be recorded) with a minimum size of: 
• 10 mm by CT scan (CT scan slice thickness no greater than 5 mm) 
• 10 mm caliper measurement by clinical exam (lesions which cannot be accurately measured 
with calipers should be recorded as non-measurable) 
• 20 mm by chest X-ray 
Malignant lymph nodes:  To be considered pathologically enlarged and measurable, a lymph 
node must be 15 mm in short axis when assessed by CT scan (CT scan slice thickness 
recommended to be no greater than 5 mm). At baseline and in follow-up, only the short axis will 
be measured and followed. See also section below on ‘Baseline documentation of target and 
non-target lesions’ for information on lymph node measurement. 
Non-measurable tumor lesions 
Non-measurable tumor lesions encompass small lesions (longest diameter <10 mm or 
pathological lymph nodes with 10 to <15 mm short axis) as well as truly non-measurable 
lesions. Lesions considered truly non-measurable include:  leptomeningeal disease, ascites, 
pleural or pericardial effusion, inflammatory breast disease, lymphangitic involvement of skin or 
lung, peritoneal spread, abdominal masses/abdominal organomegaly identified by physical exam 
that is not measurable by reproducible imaging techniques. 
Special considerations regarding lesion measurability 
Bone lesions, cystic lesions, and lesions previously treated with local therapy require particular 
comment: 

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Bone lesions: 
• Bone scan, PET scan or plain films are not considered adequate imaging techniques to 
measure bone lesions. However, these techniques can be used to confirm the presence or 
disappearance of bone lesions. 
• Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, 
that can be evaluated by cross sectional imaging techniques such as CT or MRI can be 
considered as measurable lesions if the soft tissue component meets the definition of 
measurability described above. 
• Blastic bone lesions are non-measurable. 
Cystic lesions: 
• Lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor non-measurable) since they are, by 
definition, simple cysts 
• ‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable 
lesions, if they meet the definition of measurability described above. However, if non-cystic 
lesions are present in the same subject, these are preferred for selection as target lesions 
Lesions with prior local treatment: 
• Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-
regional therapy, are usually not considered measurable unless there has been demonstrated 
progression in the lesion. Study protocols should detail the conditions under which such 
lesions would be considered measurable. 
Specifications by methods of measurements 
Measurement of lesions 
All measurements should be recorded in metric notation, using calipers if clinically assessed. All 
baseline evaluations should be performed as close as possible to the treatment start and never 
more than 4 weeks before the beginning of the treatment. 
Method of assessment 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging based evaluation should 
always be done rather than clinical examination unless the lesion(s) being followed cannot be 
imaged but are assessable by clinical exam. 
Clinical lesions:  Clinical lesions will only be considered measurable when they are superficial 
and 10 mm diameter as assessed using calipers (e.g., skin nodules). For the case of skin lesions, 

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documentation by color photography including a ruler to estimate the size of the lesion is 
suggested. As noted above, when lesions can be evaluated by both clinical exam and imaging, 
imaging evaluation should be undertaken since it is more objective and may also be reviewed at 
the end of the study. 
Chest X-ray:  Chest CT is preferred over chest X-ray, particularly when progression is an 
important endpoint, since CT is more sensitive than X-ray, particularly in identifying new 
lesions. However, lesions on chest X-ray may be considered measurable if they are clearly 
defined and surrounded by aerated lung. Still, non-contrast CT is preferred over chest X-ray. 
CT, MRI:  CT is the best currently available and reproducible method to measure lesions 
selected for response assessment. This guideline has defined measurability of lesions on CT scan 
based on the assumption that CT slice thickness is 5 mm or less. When CT scans have slice 
thickness greater than 5 mm, the minimum size for a measurable lesion should be twice the slice 
thickness. MRI is also acceptable in certain situations (e.g., for body scans). 
If prior to enrollment it is known that a subject is not able to undergo CT scans with IV contrast 
due to allergy or renal insufficiency, the decision as to whether a non-contrast CT or MRI (with 
or without IV contrast) will be used to evaluate the subject at baseline and follow-up, should be 
guided by the tumor type under investigation and the anatomic location of the disease. For 
subjects who develop contraindications to contrast after baseline contrast CT is done, the 
decision as to whether non-contrast CT or MRI (enhanced or non-enhanced) will be performed, 
should also be based on the tumor type, anatomic location of the disease and should be optimized 
to allow for comparison to the prior studies if possible. Each case should be discussed with the 
radiologist to determine if substitution of these other approaches is possible and, if not, the 
subject should be considered not evaluable from that point forward. 
Ultrasound:  Ultrasound is not useful in assessment of lesion size and should not be used as a 
method of measurement. Ultrasound examinations cannot be reproduced in their entirety for 
independent review at a later date and, because they are operator dependent, it cannot be 
guaranteed that the same technique and measurements will be taken from 1 assessment to the 
next. If new lesions are identified by ultrasound in the course of the study, confirmation by CT or 
MRI is advised. If there is concern about radiation exposure at CT, MRI may be used instead of 
CT in selected instances. 
Endoscopy, laparoscopy:  The utilization of these techniques for objective tumor evaluation is 
not advised. However, they can be useful to confirm complete pathological response when 
biopsies are obtained or to determine relapse in trials where recurrence following complete 
response or surgical resection is an endpoint. 
Tumor markers:  Tumor markers alone cannot be used to assess objective tumor response. If 
markers are initially above the upper normal limit, however, they must normalize for a subject to 
be considered in complete response. Because tumor markers are disease specific, instructions for 
their measurement should be incorporated into protocols on a disease specific basis. Specific 

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guidelines for both CA-125 response (in recurrent ovarian cancer) and PSA response (in 
recurrent prostate cancer), have been published. In addition, the Gynecologic Cancer Intergroup 
has developed CA-125 progression criteria which are to be integrated with objective tumor 
assessment for use in first-line trials in ovarian cancer. 
Cytology, histology:  These techniques can be used to differentiate between PR and CR in rare 
cases if required by protocol (for example, residual lesions in tumor types such as germ cell 
tumors, where known residual benign tumors can remain). When effusions are known to be a 
potential adverse effect of treatment (e.g., with certain taxane compounds or angiogenesis 
inhibitors), the cytological confirmation of the neoplastic origin of any effusion that appears or 
worsens during treatment can be considered if the measurable tumor has met criteria for response 
or stable disease in order to differentiate between response (or stable disease) and progressive 
disease. 
Tumor response evaluation 
Assessment of overall tumor burden and measurable disease 
To assess objective response or future progression, it is necessary to estimate the overall tumor 
burden at baseline and use this as a comparator for subsequent measurements. Only subjects with 
measurable disease at baseline should be included in protocols where objective tumor response is 
the primary endpoint. Measurable disease is defined by the presence of at least 1 measurable 
lesion (as detailed above). In studies where the primary endpoint is tumor progression (either 
time to progression or proportion with progression at a fixed date), the protocol must specify if 
entry is restricted to those with measurable disease or whether subjects having non-measurable 
disease only are also eligible. 
Baseline documentation of ‘target’ and ‘non-target’ lesions 
When more than 1 measurable lesion is present at baseline all lesions up to a maximum of 
five lesions total (and a maximum of 2 lesions per organ) representative of all involved organs 
should be identified as target lesions and will be recorded and measured at baseline. 
This means in instances where subjects have only 1 or 2 organ sites involved a maximum of 
2 (1 site) and 4 lesions (2 sites), respectively, will be recorded. Other lesions in that organ will be 
recorded as non-measurable lesions (even if size is greater than 10 mm by CT scan). 
Target lesions should be selected on the basis of their size (lesions with the longest diameter), be 
representative of all involved organs, but in addition should be those that lend themselves to 
reproducible repeated measurements. It may be the case that, on occasion, the largest lesion 
does not lend itself to reproducible measurement in which circumstance the next largest lesion 
which can be measured reproducibly should be selected. 
Lymph nodes merit special mention since they are normal anatomical structures which may be 
visible by imaging even if not involved by tumor. Pathological nodes which are defined as 

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measurable and may be identified as target lesions must meet the criterion of a short axis of 
15 mm by CT scan. Only the short axis of these nodes will contribute to the baseline sum. The 
short axis of the node is the diameter normally used by radiologists to judge if a node is involved 
by solid tumor. Nodal size is normally reported as 2 dimensions in the plane in which the image 
is obtained (for CT scan this is almost always the axial plane; for MRI the plane of acquisition 
may be axial, sagittal or coronal). The smaller of these measures is the short axis. For example, 
an abdominal node which is reported as being 20 mm x 30 mm has a short axis of 20 mm and 
qualifies as a malignant, measurable node. In this example, 20 mm should be recorded as the 
node measurement. All other pathological nodes (those with short axis 10 mm but <15 mm) 
should be considered non-target lesions. Nodes that have a short axis <10 mm are considered 
non-pathological and should not be recorded or followed. 
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted above, only the short axis is added into the sum. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease. 
All other lesions (or sites of disease) including pathological lymph nodes should be identified as 
non-target lesions and should also be recorded at baseline. Measurements are not required, and 
these lesions should be followed as ‘present’, ‘absent’, or in rare cases ‘unequivocal 
progression.’ In addition, it is possible to record multiple non-target lesions involving the same 
organ as a single item on the case report form (e.g., ‘multiple enlarged pelvic lymph nodes’ or 
‘multiple liver metastases’). 
Response criteria 
This section provides the definitions of the criteria used to determine objective tumor response 
for target lesions. 
Evaluation of target lesions 
• Complete Response (CR):  Disappearance of all target lesions. Any pathological lymph 
nodes (whether target or non-target) must have reduction in short axis to <10 mm. 
• Partial Response (PR):  At least a 30% decrease in the sum of diameters of target lesions, 
taking as reference the baseline sum diameters. 
• Progressive Disease (PD):  At least a 20% increase in the sum of diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate 
an absolute increase of at least 5 mm. (Note:  the appearance of 1 or more new lesions is also 
considered progression). 
• Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study. 

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Special notes on the assessment of target lesions 
Lymph nodes:  Lymph nodes identified as target lesions should always have the actual short axis 
measurement recorded (measured in the same anatomical plane as the baseline examination), 
even if the nodes regress to below 10 mm on study. This means that when lymph nodes are 
included as target lesions, the ‘sum’ of lesions may not be zero even if complete response criteria 
are met, since a normal lymph node is defined as having a short axis of <10 mm. Case report 
forms or other data collection methods may therefore be designed to have target nodal lesions 
recorded in a separate section where, in order to qualify for CR, each node must achieve a short 
axis <10 mm. For PR, SD, and PD, the actual short axis measurement of the nodes is to be 
included in the sum of target lesions. 
Target lesions that become ‘too small to measure’:  while on study, all lesions (nodal and 
non-nodal) recorded at baseline should have their actual measurements recorded at each 
subsequent evaluation, even when very small (e.g., 2 mm). However, sometimes lesions or 
lymph nodes which are recorded as target lesions at baseline become so faint on CT scan that the 
radiologist may not feel comfortable assigning an exact measure and may report them as being 
‘too small to measure’. When this occurs, it is important that a value be recorded on the case 
report form: 
• If it is the opinion of the radiologist that the lesion has likely disappeared, the measurement 
should be recorded as 0 mm. If the lesion is believed to be present and is faintly seen but too 
small to measure, a default value of 5 mm should be assigned and BML (below measurable 
limit) should be ticked (Note:  It is less likely that this rule will be used for lymph nodes 
since they usually have a definable size when normal and are frequently surrounded by fat 
such as in the retroperitoneum; however, if a lymph node is believed to be present and is 
faintly seen but too small to measure, a default value of 5 mm should be assigned in this 
circumstance as well and BML should also be ticked). 
This default value is derived from the 5 mm CT slice thickness (but should not be changed with 
varying CT slice thickness). The measurement of these lesions is potentially non-reproducible, 
therefore providing this default value will prevent false responses or progressions based upon 
measurement error. 
To reiterate, however, if the radiologist is able to provide an actual measure, that should be 
recorded, even if it is below 5 mm and in that case BML should not be ticked. (BML is 
equivalent to a less than sign <) 
Lesions that split or coalesce on treatment:  when non-nodal lesions ‘fragment’, the longest 
diameters of the fragmented portions should be added together to calculate the target lesion sum. 
Similarly, as lesions coalesce, a plane between them may be maintained that would aid in 
obtaining maximal diameter measurements of each individual lesion. If the lesions have truly 
coalesced such that they are no longer separable, the vector of the longest diameter in this 
instance should be the maximal longest diameter for the ‘coalesced lesion’. 

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Evaluation of non-target lesions 
This section provides the definitions of the criteria used to determine the tumor response for the 
group of non-target lesions. While some non-target lesions may actually be measurable, they 
need not be measured and instead should be assessed only qualitatively at the time points 
specified in the protocol. 
Complete Response (CR):  Disappearance of all non-target lesions and normalization of tumor 
marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). 
Non-CR/Non-PD:  Persistence of 1 or more non-target lesion(s) and/or maintenance of tumor 
marker level above the normal limits. 
Progressive Disease (PD):  Unequivocal progression of existing non-target lesions.  
(Note:  the appearance of 1 or more new lesions is also considered progression). 
Special notes on assessment of progression of non-target disease 
The concept of progression of non-target disease requires additional explanation as follows: 
When the subject also has measurable disease:  in this setting, to achieve ‘unequivocal 
progression’ on the basis of the non-target disease, there must be an overall level of 
substantial worsening in non-target disease in a magnitude that, even in presence of SD or 
PR in target disease, the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy. A modest ‘increase’ in the size of 1 or more non-target lesions is 
usually not sufficient to qualify for unequivocal progression status. The designation of overall 
progression solely on the basis of change in non-target disease in the face of SD or PR of target 
disease will therefore be extremely rare. 
When the subject has only non-measurable disease:  this circumstance arises in some phase III 
trials when it is not a criterion of study entry to have measurable disease. The same general 
concepts apply here as noted above, however, in this instance there is no measurable disease 
assessment to factor into the interpretation of an increase in non-measurable disease burden. 
Because worsening in non-target disease cannot be easily quantified (by definition:  if all lesions 
are truly non-measurable) a useful test that can be applied when assessing subjects for 
unequivocal progression is to consider if the increase in overall disease burden based on the 
change in non-measurable disease is comparable in magnitude to the increase that would be 
required to declare PD for measurable disease:  i.e., an increase in tumor burden representing an 
additional 73% increase in ‘volume’ (which is equivalent to a 20% increase diameter in a 
measurable lesion). Examples include an increase in a pleural effusion from ‘trace’ to ‘large’, an 
increase in lymphangitic disease from localized to widespread, or may be described in protocols 
as ‘sufficient to require a change in therapy’. If ‘unequivocal progression’ is seen, the subject 
should be considered to have had overall PD at that point. While it would be ideal to have 

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objective criteria to apply to non-measurable disease, the very nature of that disease makes it 
impossible to do so; therefore, the increase must be substantial. 
New lesions 
The appearance of new malignant lesions denotes disease progression; therefore, some 
comments on detection of new lesions are important. There are no specific criteria for the 
identification of new radiographic lesions; however, the finding of a new lesion should be 
unequivocal:  i.e., not attributable to differences in scanning technique, change in imaging 
modality or findings thought to represent something other than tumor (for example, some ‘new’ 
bone lesions may be simply healing or flare of pre-existing lesions). This is particularly 
important when the subject’s baseline lesions show partial or complete response. For example, 
necrosis of a liver lesion may be reported on a CT scan report as a ‘new’ cystic lesion, which it is 
not. 
A lesion identified on a follow-up study in an anatomical location that was not scanned at 
baseline is considered a new lesion and will indicate disease progression. An example of this is 
the subject who has visceral disease at baseline and while on study has a brain CT or MRI 
ordered which reveals metastases. The subject’s brain metastases are considered to be evidence 
of PD even if he/she did not have brain imaging at baseline. 
If a new lesion is equivocal, for example because of its small size, continued therapy and follow-
up evaluation will clarify if it represents truly new disease. If repeat scans confirm there is 
definitely a new lesion, then progression should be declared using the date of the initial scan. 
(18)F-Fluorodeoxyglucose Positron Emission Tomography (FDGPET) 
While FDG-PET response assessments need additional study, it is sometimes reasonable to 
incorporate the use of FDG-PET scanning to complement CT scanning in assessment of 
progression (particularly possible ‘new’ disease). New lesions on the basis of FDG-PET imaging 
can be identified according to the following algorithm: 
• Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD based 
on a new lesion. 
• No FDG-PET at baseline and a positive FDG-PET at follow-up: 
• If the positive FDG-PET at follow-up corresponds to a new site of disease confirmed by 
CT, this is PD. 
• If the positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, 
additional follow-up CT scans are needed to determine if there is truly progression 
occurring at that site (if so, the date of PD will be the date of the initial abnormal FDG-
PET scan). 
• If the positive FDG-PET at follow-up corresponds to a pre-existing site of disease on CT 
that is not progressing on the basis of the anatomic images, this is not PD. 

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Evaluation of best overall response 
The best overall response is the best response recorded from the start of the study treatment until 
the end of treatment taking into account any requirement for confirmation. On occasion a 
response may not be documented until after the end of therapy so protocols should be clear if 
post-treatment assessments are to be considered in determination of best overall response. 
Protocols must specify how any new therapy introduced before progression will affect best 
response designation. The subject’s best overall response assignment will depend on the findings 
of both target and non-target disease and will also take into consideration the appearance of new 
lesions. Furthermore, depending on the nature of the study and the protocol requirements, it may 
also require confirmatory measurement. Specifically, in nonrandomized trials where response is 
the primary endpoint, confirmation of PR or CR is needed to deem either 1 the ‘best overall 
response’ (Table 15). 
Time point response 
It is assumed that at each protocol specified time point, a response assessment occurs. Table 11 
provides a summary of the overall response status calculation at each time point for subjects who 
have measurable disease at baseline. 
When subjects have non-measurable (therefore non-target) disease only, Table 12 is to be used. 
Missing assessments and not-evaluable designation 
When no imaging/measurement is done at all at a particular time point, the subject is not 
evaluable at that time point. If only a subset of lesion measurements are made at an assessment, 
usually the case is also considered not evaluable at that time point, unless a convincing argument 
can be made that the contribution of the individual missing lesion(s) would not change the 
assigned time point response. This would be most likely to happen in the case of PD. 
For example, if a subject had a baseline sum of 50 mm with 3 measured lesions and at follow-up 
only 2 lesions were assessed, but those gave a sum of 80 mm, the subject will have achieved PD 
status, regardless of the contribution of the missing lesion. 
If 1 or more target lesions were not assessed either because the scan was not done or could not be 
assessed because of poor image quality or obstructed view, the Response for Target Lesions 
should be “Unable to Assess” since the subject is not evaluable. Similarly, if 1 or more 
non-target lesions are indicated as ‘not assessed’, the response for non-target lesions should be 
“Unable to Assess” (except where there is clear progression). Overall response would be 
“Unable to Assess” if either the target response or the non-target response is “Unable to Assess” 
(except where this is clear evidence of progression) as this equates with the case being not 
evaluable at that time point. 

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Best overall response:  all time points 
The best overall response will be determined by statistical programming once all the data for the 
subject is known. 
Table 11: 
Time Point Response:  Subjects with Targets (± Non-target) Disease 
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/Non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all evaluated 
No 
PR 
SD 
Non-PD or not all evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
CR = complete response; NE = inevaluable; PD = progressive disease; PR = partial response; SD = stable disease 
 
Table 12: 
Time Point Response:  Subjects with Non-target Disease Only 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/Non-PD 
No 
Non-CR/Non-PDa 
Not all evaluated 
No 
NE 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
CR = complete response; NE = inevaluable; PD = progressive disease; PR = partial response; SD = stable disease 
a 
‘Non-CR/Non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is increasingly used as 
endpoint for assessment of efficacy in some trials so to assign this category when no lesions can be measured is 
not advised. 

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Table 13: 
Best Overall Response When Confirmation of CR and PR Required 
Overall Response 
First Time Point 
Overall Response 
Subsequent  
Time Point 
BEST Overall Response 
CR 
CR 
CR 
CR 
PR 
SD, PD or PRa 
CR 
SD 
SD provided minimum criteria for SD duration met, otherwise, PD 
CR 
PD 
SD provided minimum criteria for SD duration met, otherwise, PD 
CR 
NE 
SD provided minimum criteria for SD duration met, otherwise, NE 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 
PR 
PD 
SD provided minimum criteria for SD duration met, otherwise, PD 
PR 
NE 
SD provided minimum criteria for SD duration met, otherwise, NE 
NE 
NE 
NE 
CR = complete response; NE = inevaluable; PD = progressive disease; PR = partial response; SD = stable disease 
a 
If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting 
PR criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after 
CR). Best response would depend on whether minimum duration for SD was met. However, sometimes ‘CR’ 
may be claimed when subsequent scans suggest small lesions were likely still present and in fact the subject had 
PR, not CR at the first time point. Under these circumstances, the original CR should be changed to PR and the 
best response is PR. 
 
Special notes on response assessment 
When nodal disease is included in the sum of target lesions and the nodes decrease to ‘normal’ 
size (<10 mm), they may still have a measurement reported on scans. This measurement should 
be recorded even though the nodes are normal in order not to overstate progression should it be 
based on increase in size of the nodes. As noted earlier, this means that subjects with CR may not 
have a total sum of ‘zero’ on the case report form (CRF). 
In trials where confirmation of response is required, repeated ‘NE’ time point assessments may 
complicate best response determination. The analysis plan for the trial must address how missing 
data/assessments will be addressed in determination of response and progression. For example, 
in most trials it is reasonable to consider a subject with time point responses of PR-NE-PR as a 
confirmed response. 
Subjects with a global deterioration of health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be reported as 
‘symptomatic deterioration’. Every effort should be made to document objective progression 
even after discontinuation of treatment. Symptomatic deterioration is not a descriptor of an 
objective response:  it is a reason for stopping study therapy. The objective response status of 
such subjects is to be determined by evaluation of target and non-target disease as shown in 
Table 11, Table 12, and Table 13. 

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Conditions that define ‘early progression, early death and non-evaluability’ are study specific 
and should be clearly described in each protocol (depending on treatment duration, treatment 
periodicity). 
In some circumstances it may be difficult to distinguish residual disease from normal tissue. 
When the evaluation of complete response depends upon this determination, it is recommended 
that the residual lesion be investigated (fine needle aspirate/biopsy) before assigning a status of 
complete response. FDG-PET may be used to upgrade a response to a CR in a manner similar to 
a biopsy in cases where a residual radiographic abnormality is thought to represent fibrosis or 
scarring. The use of FDG-PET in this circumstance should be prospectively described in the 
protocol and supported by disease specific medical literature for the indication. However, it must 
be acknowledged that both approaches may lead to false positive CR due to limitations of 
FDG-PET and biopsy resolution/sensitivity. 
For equivocal findings of progression (e.g., very small and uncertain new lesions; cystic changes 
or necrosis in existing lesions), treatment may continue until the next scheduled assessment. If at 
the next scheduled assessment, progression is confirmed, the date of progression should be the 
earlier date when progression was suspected. 

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APPENDIX 4: 
DRUGS CLEARLY ASSOCIATED WITH THE RISK OF 
TORSADES DE POINTES (TDP) AND QT PROLONGATION 
 
Anti-arrhythmics 
- Amiodarone 
- Disopyramide 
- Dofetilide 
- Dronedarone 
- Flecainide 
- Ibutilide 
- Procainamide (Oral off US mkt) 
- Quinidine 
- Sotalol 
- Ritonavir 
- Indinavir 
- Nelfinavir 
Antimicrobials 
- Azithromycin 
- Ciprofloxacin 
- Clarithromycin 
- Erythromycin 
- Grepafloxacin (Off market worldwide) 
- Levofloxacin 
- Moxifloxacin 
- Sparfloxacin (Removed from US Market) 
- Pentamidine 
- Fluconazole 
Anti-psychotics 
- Haloperidol 
- Mesoridazine (Removed from US Market) 
- Pimozide 
- Thioridazine 
- Chlorpromazine 
- Droperidol 
- Sulpiride (On non US Market) 
Anti-cancers 
- Arsenic trioxide 
- Vandetanib 
Anti-depressants, SSRIs 
- Citalopram 
- Escitalopram 
Antihistamines 
- Astemizole (Removed from US Market) 
- Terfenadine (Removed from US Market) 
Anti-malarials 
- Chloroquine 
- Halofantrine 
Antilipemic 
- Probucol (Removed from US Market) 
- Ondansetron 
Opiates 
- Levomethadyl acetate (Removed from US Market) 
- Methadone 
Anesthetics, general 
- Propofol 
- Sevoflurane 
Others 
- Cisapride (Removed from US Market) 
- Cocaine 
- Anagrelide 
- Bepridil (Removed from US Market) 
- Domperidone (On non US Market) 
 
This list is not comprehensive and subject to change and all medications should be reviewed 
prior to administering. CredibleMeds® OncoSupport™ can be used as a reference for additional 
information of drugs with known TdP risk. 

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APPENDIX 5: 
ECOG PERFORMANCE STATUS 
These scales and criteria are used by doctors and researchers to assess how a subject's disease is 
progressing, assess how the disease affects the daily living abilities of the subject, and determine 
appropriate treatment and prognosis. They are included here for health care professionals to 
access. 
ECOG PERFORMANCE STATUS* 
Grade ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work 
of a light or sedentary nature, e.g., light housework, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities. 
Up and about more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking 
hours 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair 
5 
Dead 
* As published in Oken 1982. 
 
The ECOG Performance Status is in the public domain therefore available for public use. To duplicate the scale, 
please cite the reference above and credit the Eastern Cooperative Oncology Group, Robert Comis M.D., Group 
Chair. 
 
All contents copyright © 1998-2000 Eastern Cooperative Oncology Group. 
All rights reserved. 
Revised:  July 27, 2006 

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APPENDIX 6: 
PCWG3 CASTRATION-RESISTANT PROSTATE CANCER 
CLINICAL TRIAL RECOMMENDATIONS AND CRITERIA 
 

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Table 2. Standard Baseline Disease Assessments Recommended by PCWG3 in Comparison With PCWG2 Recommendations 
Assessment 
PCWG2 (2008) 
PCWG3 (2015) 
Histology 
Not addressed 
Adenocarcinoma 
Adenocarcinoma with small-cell or neuroendocrine features  
Small-cell carcinoma 
Report Gleason sum for primary 
Consider rebiopsy of metastatic disease 
Clinical 
History and physical examination 
Age, pain, analgesic consumption, performance status, comorbidity assessment, history, and physical 
examination; prior local therapy; TNM stage at diagnosis; and PSA 
Prior systemic treatment 
Pre- and postchemotherapy 
Record each line of systemic therapy (single agent or combination) in order of administration, 
including start and stop dates, dose(s), and schedule(s), the disease state in which it was 
administered, and response (resistant v sensitive) on the basis of PSA if appropriate 
Record type of progression on prior therapy (PSA, radiographic [bone, nodal, visceral], clinical [eg, pain 
escalation]) 
Prior radiation therapy 
Not addressed 
Site, administered dose per fraction and treatment duration 
Blood-based biomarkers 
PSA 
Testosterone 
Host:  CBC with differential, ALK, kidney/liver function, albumin, LDH, testosterone* 
Tumor:  PSA and cPSA kinetics 
Optional:  CEA, chromogranin A, neuron-speciﬁc enolase, CTC enumeration 
Imaging 
 
 
Prostate/prostate bed 
Endorectal MRI 
Retained, cross-sectional imaging of prostate region if applicable 
Nodal 
CT: Only nodes ≥ 2 cm were 
assessed for change in size 
CT or MRI: 
Nodes ≥ 1.5 cm in the short axis are considered measurable; nodes ≥ 1.0 and less than 1.5 cm in the 
short axis are considered pathologic according to clinical discretion, and nontarget; nodes less than 
1.0 cm in the short axis are nonpathologic 
Record pelvic and extrapelvic (retroperitoneal, mediastinal, thoracic, other) nodal disease separately; 
up to ﬁve nodes in total 
Record new lesions v growth of pre-existing lesions, and sites of new lesions 
Visceral 
CT: reported as visceral per RECIST 
CT or MRI: 
Record individual sites of spread (lung, liver, adrenal, CNS) separately; up to ﬁve lesions per site 
Lesions ≥ 1.0 cm in the longest dimension are considered measurable 
Record new lesions v growth of pre-existing lesions, and sites of new lesions 
Bone 
99mTc MDP 
Record new lesions and sites of new lesions 
(continued on following page) 

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Table 2. Standard Baseline Disease Assessments Recommended by PCWG3 in Comparison With PCWG2 Recommendations (continued) 
Assessment 
PCWG2 (2008) 
PCWG3 (2015) 
Tumor proﬁling for determinants of prognostic, 
predictive, and resistance biomarkers 
Not addressed 
Consider rebiopsy of metastatic or locally recurrent lesion(s) for biologic characterization 
Patient-reported outcomes 
None 
Pain assessment, opiate analgesia consumption, physical functioning (functional status), health-related 
quality of life; consider fatigue and PRO-CTCAE. Validated PRO instruments strongly recommended 
Abbreviations:  ALK, alkaline phosphatase; CBC, complete blood count; CEA, carcinoembryonic antigen; CT, computed tomography; CTCs, circulating tumor cells; CTCAE, Common Terminology 
Criteria for Adverse Events; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; PCWG2, Prostate Cancer Clinical Trials Working Group 2; PCWG3, Prostate Cancer Clinical Trials 
Working Group 3; PRO, patient-reported outcome; PRO-CTCAE, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events; PSA, prostate-speciﬁc antigen; 
RECIST, Response Evaluation Criteria in Solid Tumors; 99mTc MDP, 99mTc methylene diphosphonate. 
*Ultrasensitive testosterone measures may be indicated where appropriate on the basis of drug under study and context. 
Source:  Scher 2016 

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Table 3. Criteria for Progression at Trial Entry by Disease Manifestation 
Variable 
PCWG2 (2008) 
PCWG3 (2015) 
Blood-based 
 
 
PSA 
Obtain sequence of rising values at a minimum of 1-week 
intervals 
Retained 
 
2.0 ng/mL minimal starting value 
1.0 ng/mL is the minimal starting value if conﬁrmed rise is only indication of progression 
unless pure small-cell carcinoma 
 
Estimate pretherapy PSADT if at least three values available 
≥ 4 weeks apart 
Retained 
Imaging 
 
 
Nodes 
Nodal progression sufﬁcient for trial entry independent of PSA 
Retained 
 
Measurable lesions not required for entry 
Retained 
 
Use RECIST to record nodal lesions as target or nontarget 
Modiﬁed RECIST 1.1 criteria, separate pelvic and extrapelvic disease, up to ﬁve nodal 
lesions total recorded 
 
Only lymph nodes ≥ 2 cm in diameter (long axis) were actionable 
as progressive disease 
Previously normal (< 1.0-cm) lymph nodes must have grown by ≥ 5 mm in the short axis 
from baseline or nadir and be ≥ 1.0 cm in the short axis to be considered to have 
progressed 
If the node progresses to ≥ 1.5 cm in the short axis, it is measurable; nodes that have 
progressed to 1.0 to less than 1.5 cm are pathologic, subject to clinical discretion, and 
nonmeasurable 
For existing pathologic adenopathy, progression is deﬁned per RECIST  1.1 
 
Record presence of nodal and/or visceral disease separately 
Retained with modiﬁcation  
Nodal sites: 
Locoregional: pelvic only 
Extrapelvic: retroperitoneal, mediastinal, thoracic, or other 
Viscera 
Visceral progression sufﬁcient for trial entry independent of PSA 
Retained but recorded separately by site of spread (lung, liver, adrenal, CNS); up to ﬁve 
lesions per site of spread 
 
Measurable lesions not required for entry 
Retained 
 
Use RECIST to record visceral lesions as target or nontarget 
Retained 
 
Record presence of nodal and/or visceral disease separately 
Retained with modiﬁcation 
Visceral sites: lung, liver, adrenal, CNS 
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Table 3. Criteria for Progression at Trial Entry by Disease Manifestation (continued) 
Variable 
PCWG2 (2008) 
PCWG3 (2015) 
Prostate/prostate bed 
(primary site) 
Record prior treatment of primary tumor 
Retained 
Perform directed pelvic imaging (CT, MRI, PET/CT, endorectal 
MRI, transrectal ultrasound) to document presence or absence 
of disease 
Retained 
Bone 
Two new lesions 
Retained  
 
Conﬁrm ambiguous results by other imaging modalities (eg, CT or 
MRI) 
Retained, but only positivity on the bone scan deﬁnes metastatic disease to bone 
Other sites of disease 
Patients with treated epidural lesions and no other epidural 
progression are eligible 
Retained 
Type of progression at trial entry Not addressed 
Report separately:  
PSA only 
Bone only ± nodal disease 
Nodal disease only (no bone disease present) 
Visceral (lung, liver, adrenal, CNS) disease (± other sites) 
Record new lesions and site of new lesions v growth of pre- existing lesions, or both 
Other markers 
 
 
Patient-reported outcomes 
Not addressed 
For pain palliation analyses, presence of clinically meaningful pain at baseline (eg, ≥ 4 on a 
10-point pain intensity scale) is a prerequisite; for pain progression analyses, patients 
may have any level of pain at baseline, including no pain 
Abbreviations:  CT, computed tomography; MRI, magnetic resonance imaging; PCWG2, Prostate Cancer Clinical Trials Working Group 2; PCWG3, Prostate Cancer Clinical Trials Working Group 3; 
PET, positron emission tomography; PSA, prostate-speciﬁc antigen; PSADT, PSA doubling time; RECIST, Response Evaluation Criteria in Solid Tumors. 
Source:  Scher 2016 

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Table 5. Suggested Outcome Measures for Clinical Trials in Metastatic Prostate Cancer:  Report by Disease Manifestation 
Variable 
PCWG2 (2008) 
PCWG3 (2015) 
Histology 
Not addressed 
Encourage rebiopsy of metastatic sites or local recurrence at progression to 
evaluate for histologic (ie, neuroendocrine/small cell) transformation; in 
the context of clinical trials, encourage rebiopsy for biomarker assessment 
Blood-based markers  
 
 
PSA 
Recognize that a favorable effect on PSA may be delayed for ≥ 12 weeks, 
even for a cytotoxic drug 
Retained 
 
Monitor PSA by cycle but plan to continue through early rises for a 
minimum of 12 weeks unless other evidence of progression 
Retained 
 
Ignore early rises (before 12 weeks) in determining PSA response 
Retained 
 
For control/relieve/eliminate end points: 
For control/relieve/eliminate end points: 
 
Record the percent change from baseline (rise or fall) at 12 weeks, 
and separately, the maximal change (rise or fall) at any time using a 
waterfall plot 
Retained, except with timing (8-9 or 12 weeks) depending on trial design 
 
 
Separately report the proportion of patients who have undergone radical 
prostatectomy and achieved a nadir less than 0.2 ng/mL v primary 
radiation therapy–treated patients who achieved a nadir less than 
0.5 ng/mL 
Describe absolute changes in PSA over time from baseline to best response 
 
For delay/prevent end points (progression): 
For delay/prevent end points (progression): 
 
After decline from baseline: record time from start of therapy to ﬁrst 
PSA increase that is ≥ 25% and ≥ 2 ng/mL above the nadir, and 
which is conﬁrmed by a second value ≥ 3 weeks later (ie, a 
conﬁrmed rising trend); the requirement for an increase of 5 ng/mL 
was decreased to 2 ng/mL, and the requirement for a 50% increase 
was reduced to 25% 
Retained (standards for reporting PSA progression date may not indicate a 
need to stop treatment) 
 
Recording the duration of PSA decline of little value 
Retained 
 
No decline from baseline: PSA progression ≥ 25% increase and ≥ 2 ng/mL 
increase from baseline beyond 12 weeks 
Relate to mechanism of drug and anticipated timing of potential 
favorable/unfavorable effects on PSA, if present 
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Table 5. Suggested Outcome Measures for Clinical Trials in Metastatic Prostate Cancer:  Report by Disease Manifestation (continued) 
Variable 
PCWG2 (2008) 
PCWG3 (2015) 
CTC 
Not addressed 
Enumerate at the start of treatment: Record as favorable (four or fewer cells 
per 7.5 mL of blood) or unfavorable (ﬁve or more cells per 7.5 mL) 
If unfavorable, monitor for changes after treatment 
For control/relieve/eliminate end points: 
Report as change from unfavorable (ﬁve or more cells per 7.5 mL of blood) 
to favorable (four or fewer cells per 7.5 mL) and separately, the percent 
change from baseline using a waterfall plot 
For delay/prevent end points: no validated deﬁnition exists (however, rising 
CTC counts are associated with a poor prognosis) 
LDH, total alkaline phosphatase, 
bone-speciﬁc alkaline 
phosphatase, urine N-telopeptide, 
hemoglobin, NLR 
Not addressed 
Descriptively report changes over time, may include the proportion showing 
normalization of a given biomarker and/or waterfall plots of percent 
change from baseline in a given biomarker 
Report institutional normal ranges to determine normalization of a given 
biomarker 
Imaging biomarkers: nodal and visceral 
For control/relieve/eliminate end 
points 
 
 
General 
Record changes in nodal sites separately from visceral sites 
Record changes in lymph nodes, lung, liver, adrenal, and CNS sites separately 
 
Use RECIST with caveats: 
Record up to ﬁve lesions per site of disease 
 
 
Record changes in size using waterfall plot  
Conﬁrm favorable change with second scan 
Record complete elimination of disease at any site separately 
Use RECIST 1.1 with caveats: 
Record changes in size using waterfall plot 
Conﬁrm favorable change with second scan 
Record complete elimination of disease at any site separately 
Nodes 
Only report changes in lymph nodes that were ≥ 2 cm in the long axis at 
baseline 
Only report changes in lymph nodes that were ≥ 1.5 cm in the short axis 
Record changes in pelvic (regional) nodes v extrapelvic (distant/metastatic) 
nodes separately 
Visceral 
Use RECIST with caveats above 
Use RECIST 1.1 with caveats: 
Record changes in liver, lung, adrenal, and CNS separately  
Only report changes in lesions ≥ 1.0 cm in the longest dimension 
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Table 5. Suggested Outcome Measures for Clinical Trials in Metastatic Prostate Cancer:  Report by Disease Manifestation (continued) 
Variable 
PCWG2 (2008) 
PCWG3 (2015) 
For delay/prevent end points  
 
 
Nodal and visceral 
Use RECIST criteria for progression, with additional requirement that 
progression be conﬁrmed by a second scan ≥ 6 weeks later (the 
second scan is particularly important when anticipated effect on PSA 
is delayed, or for biologic therapies) 
General: 
Record changes in nodal and visceral (lung, liver, adrenal, and CNS) disease 
separately 
Use RECIST 1.1 but clearly record type of progression (growth of existing 
lesions v development of new lesions) separately by site 
The recommendations apply to both nmCRPC and mCRPC  
Record up to ﬁve lesions per site of spread 
Report the proportion who have not progressed at ﬁxed time points (6 or 
12 months) 
 
Note that for some treatments, a lesion may increase in size before it 
decreases 
Retained 
Nodal 
As above 
Previously normal (< 1.0-cm) lymph nodes must have grown by ≥ 5 mm in the 
short axis from baseline or nadir and be ≥ 1.0 cm in the short axis to be 
considered to have progressed 
Nodes that have progressed to 1.0 to less than 1.5 cm are pathologic, subject 
to clinical discretion, and nonmeasurable 
For existing pathologic adenopathy (≥ 1.5 cm), progression is deﬁned per 
RECIST 1.1 
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Table 5. Suggested Outcome Measures for Clinical Trials in Metastatic Prostate Cancer:  Report by Disease Manifestation (continued) 
Variable 
PCWG2 (2008) 
PCWG3 (2015) 
Imaging biomarkers: bone 
 
 
Metastatic 
For control/relieve/eliminate end points: 
For control/relieve/eliminate end points: 
 
Record changes as improved or stable (no new lesions) or worse 
(new lesions) 
Retained with addition of resolved bone lesion 
 
Changes in intensity of uptake alone do not constitute progression or 
regression 
Retained 
 
No new lesions: continue therapy in absence of other signs of 
progression 
Retained 
 
New lesions (See Progression below) 
Retained 
 
For delay/prevent end points (progression): 
For delay/prevent end points (progression): 
 
Progression: 
Progression: 
 
Exclude pseudoprogression in the absence of symptoms or other 
signs of progression 
At least two new lesions on ﬁrst post-treatment scan, with at least 
two additional lesions on the next scan (212 rule) 
Retained 
 
If at least two additional new lesions are seen on the next 
(conﬁrmatory) scan, the date of progression is the date of the 
ﬁrst post-treatment scan, when the ﬁrst two new lesions were 
documented 
Retained 
 
For all scans after the ﬁrst post-treatment scan, at least two new 
lesions 
For scans after the ﬁrst post-treatment scan, at least two new lesions relative 
to the ﬁrst post-treatment scan conﬁrmed on a subsequent scan 
 
Date of progression is the date of the scan that ﬁrst documents the 
second lesion 
Retained 
 
Changes in intensity of uptake alone do not constitute either 
progression or regression 
Retained 
 
 
Report the proportion of patients who have not progressed at ﬁxed time 
intervals (6 and 12 months) 
nmCRPC 
Not addressed 
Nonmetastatic to metastatic progression: 
Any new unequivocal bone lesion, except if that lesion appears in the ﬁrst 
post-treatment scan; in that case, document the event, continue 
treatment until 2 additional new lesions appear, and record both events 
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Table 5. Suggested Outcome Measures for Clinical Trials in Metastatic Prostate Cancer:  Report by Disease Manifestation (continued) 
Variable 
PCWG2 (2008) 
PCWG3 (2015) 
Patient-reported outcomes 
Consider independently of other outcome measures 
Pain palliation assessment requires a patient population with clinically 
meaningful pain at baseline (eg, ≥ 4 on a 10-point pain intensity scale) and 
response deﬁned as a clinically meaningful score improvement at a 
subsequent time point (eg, a 30% relative or 2-point absolute 
improvement from baseline at 12 weeks, conﬁrmed at least 2 weeks later, 
without an overall increase in opiate use) 
 
For control/relieve/eliminate end points: 
Document pain and analgesia at entry with a lead-in period 
repeatedly at 3- to 4-week intervals 
For control/relieve/eliminate end points: 
Serial (eg, daily × 7 days) assessments at each time point can and measure 
improve the stability of values 
 
Perform serial assessments of global changes in HRQoL, urinary or bowel 
compromise, pain management, additional anticancer therapy 
Principles may be extended for any PRO for which a clinically meaningful 
baseline PRO score has been determined together with a responder 
deﬁnition that is based on a sustained clinically meaningful score 
improvement 
 
Ignore early changes (≤ 12 weeks) in pain or HRQoL in absence of 
compelling evidence of disease progression 
 
 
For delay/prevent end points: 
For delay/prevent end points: 
 
Conﬁrm response or progression of pain or HRQoL end points 
≥ 3 weeks later 
Patients with any level of baseline pain, including no pain, are eligible to be 
evaluated for prevent/delay end points; those without pain are followed 
for development of pain, whereas those with baseline pain are followed 
for progression (eg, a 2-point increase without an overall decrease in 
opiate use) 
Pain assessment should be administered at treatment discontinuation and 
once again if feasible (eg, 2 to 4 weeks later) 
Time to deterioration of physical function and/or HRQoL scores should also 
be included, with a priori thresholds deﬁning clinically meaningful 
deterioration score changes that are based on prior published data for 
the selected questionnaire 
Abbreviations:  CTC, circulating tumor cell; HRQoL, health-related quality of life; LDH, lactate dehydrogenase; mCRPC, metastatic castration-resistant prostate cancer; NLR, neutrophil/ lymphocyte 
ratio; nmCRPC, nonmetastatic castration-resistant prostate cancer; PCWG2, Prostate Cancer Clinical Trials Working Group 2; PCWG3, Prostate Cancer Clinical Trials Working Group 3;  
PRO, patient-reported outcome; PSA, prostate- speciﬁc antigen; RECIST, Response Evaluation Criteria in Solid Tumors. 
Source:  Scher 2016