Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5829 (Alobresib) as a Single Agent and In Combination With Enzalutamide in Participants With Metastatic Castrate-Resistant Prostate Cancer

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02607228
• Collaborator: (none)
• Enrollment: 31
• Locations: 4
• Arms: 5
• Actual Duration (Months): 44.8
• Patients Per Site: 7.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study consists of two phases: Dose Escalation (Phase 1b) and Dose Expansion (Phase 2)

The Dose Escalation phase will characterize the safety, tolerability, and determine the maximum tolerated dose (MTD) of alobresib as a single agent and in combination with enzalutamide, in participants with metastatic castrate-resistant prostate cancer (mCRPC).

The Dose Expansion phase will evaluate the following:

• In group 1, the efficacy of alobresib as a single agent in participants with mCRPC who have progressed while receiving enzalutamide (may have also received abiraterone)

• In group 2, the efficacy of alobresib combined with enzalutamide in participants with mCRPC who have progressed while receiving treatment with abiraterone (may not have previously received enzalutamide)

• In group 3, the efficacy of alobresib combined with enzalutamide in participants with mCRPC who have had prostate specific antigen (PSA) progression, but not radiographic progression, while receiving treatment with enzalutamide (participants may have also previously received abiraterone)

Condition or Disease	Intervention/Treatment	Phase
Metastatic Castrate-Resistant Prostate Cancer	Drug: Alobresib; Drug: Enzalutamide	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5829 as a Single Agent and In Combination With Enzalutamide in Subjects With Metastatic Castrate-Resistant Prostate Cancer
• Actual Study Start Date: Dec 8, 2015
• Actual Primary Completion Date: Oct 25, 2017
• Actual Study Completion Date: Sep 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alobresib Dose Escalation Participants who have progressed on either abiraterone and/or enzalutamide will be enrolled to receive increasing doses of alobresib up to 9 mg to determine the MTD.	Drug: Alobresib; Tablet administered orally once daily.; Other Names: GS-5829
Experimental: Alobresib + Enzalutamide Dose Escalation Following a two week lead-in with enzalutamide once daily, participants who have progressed on abiraterone will receive less than or equal to MTD of alobresib in combination with enzalutamide 160 mg once daily. Based on observed pharmacokinetics (PK) interaction, toxicity, and tolerability observed in the single agent dose escalation, the dose of alobresib may be increased.	Drug: Alobresib; Tablet administered orally once daily.; Other Names: GS-5829 ; Drug: Enzalutamide; Capsules administered orally once daily.; Other Names: XTANDI®
Experimental: Alobresib Dose Expansion (Group 1) Participants will receive a dose less than or equal to MTD of alobresib (based on safety, pharmacodynamics (PD), and tolerability).	Drug: Alobresib; Tablet administered orally once daily.; Other Names: GS-5829
Experimental: Alobresib + Enzalutamide Dose Expansion (Group 2) Participants will receive a dose less than or equal to MTD of alobresib plus enzalutamide (based on safety, PD, and tolerability).	Drug: Alobresib; Tablet administered orally once daily.; Other Names: GS-5829 ; Drug: Enzalutamide; Capsules administered orally once daily.; Other Names: XTANDI®
Experimental: Alobresib + Enzalutamide Dose Expansion (Group 3) Participants will receive alobresib plus enzalutamide (dose will be equivalent to the dose chosen for Group 2).	Drug: Alobresib; Tablet administered orally once daily.; Other Names: GS-5829 ; Drug: Enzalutamide; Capsules administered orally once daily.; Other Names: XTANDI®

Outcome Measures

Primary Outcome Measures

1. Phase 1b Dose Escalation: Number of Participants Experienced Dose Limiting Toxicities (DLTs) [Day 1 through Day 28]

   A DLT was a toxicity, considered possibly related to alobresib, and which occurred during the DLT assessment window (Days 1 through 28) in each cohort: Grade ≥ 4 neutropenia (absolute neutrophil count (ANC) < 500/mm^3), Grade ≥ 3 neutropenia (ANC< 1000/mm^3) with fever (a single temperature > 38.3°C or a sustained temperature of ≥ 38°C for more than 1 hour (h)), Grade ≥ 3 thrombocytopenia, Grade ≥ 2 bleeding (eg, gastrointestinal, respiratory, epistaxis, purpura), Grade ≥ 3 non hematologic toxicity, except- Grade 3 nausea or emesis with maximum duration of 48 h on adequate medical therapy and Grade 3 diarrhea which persists for < 72 h in the absence of maximal medical therapy, Grade ≥ 2 non hematologic treatment emergent adverse event (TEAE) that in the opinion of the investigator was of potential clinical significance such that further dose escalation would expose participants to unacceptable risk, treatment interruption ≥ 7 days due to unresolved toxicity.

2. Phase 2 Dose Expansion: Non-progression Rate at Week 24 According to Prostate Cancer Working Group (PCWG2) Criteria [Week 24]

   The non-progression rate at Week 24 was defined as the proportion of participants who did not progress by Week 24.

Secondary Outcome Measures

1. Phase 1b Dose Escalation: Cmax: Maximum Observed Plasma Concentration of Alobresib [Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Days 1 and 15]

   Cmax is the maximum observed concentration of drug in plasma.

2. Phase 1b Dose Escalation: Ctau: Observed Drug Concentration at the End of the Dosing Interval of Alobresib [Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 15]

   Ctau is the observed concentration of drug in plasma at the end of dosing.

3. Phase 1b Dose Escalation: AUClast: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration of Alobresib [Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Days 1 and 15]

   AUClast is the concentration of drug over time zero to last concentration (area under the plasma concentration versus time curve).

4. Phase 1b Dose Escalation: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Alobresib [Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 15]

   AUCtau is defined as the concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

5. Phase 1b Dose Escalation: Tmax: Time (Observed Time Point) of Cmax of Alobresib [Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Days 1 and 15]

   Tmax is the time observed for the Cmax of alobresib.

6. Percentage of Participants Who Had ≥ 30% Reduction in Prostate Specific Antigen (PSA) From Baseline at Week 12 [Baseline; Week 12]

   PSA response was defined as percentage of participants with ≥ 30% decline in PSA from baseline by 12 weeks.

7. Progression Free Survival (PFS) [Up to approximately 4 years]

   PFS was defined as the interval from first dose date of study drug to the earlier of the first documentation of definitive disease progression (assessed per PCWG2) or death from any cause. PCWG2 criteria for progression was determined as 'Decline from baseline' when record start of therapy to first prostate-specific antigen (PSA) increase that is ≥ 25% and ≥ 2 ng/mL above the nadir and confirmed by a second value 3 or more weeks later; 'No decline from baseline' when PSA progression ≥ 25% and ≥ 2 ng/mL after 12 weeks.

8. Overall Survival (OS) [Up to approximately 4 years]

   OS is defined as the interval from first dose date of study drug to death from any cause.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Histologically or cytologically confirmed prostate cancer (individuals with primary neuroendocrine carcinoma of prostate are excluded)

• Must have documented progressive disease by meeting at least one of the Prostate Cancer Working Group 2 Criteria

• Castration resistant disease defined as ongoing androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy and serum testosterone level ≤ 1.73 nmol/l (50 ng/dL) at screening visit. Individuals who have not had a bilateral orchiectomy must have a plan to maintain effective GnRH-analogue therapy for the duration of the trial.

• Metastatic disease documented by bone lesions on bone scan or by measurable soft tissue disease by computerized tomography/magnetic resonance imaging (CT/MRI). Patients whose disease spread is limited to regional pelvic lymph nodes are not eligible

• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1

• Adequate organ function defined as follows:

• Hematologic: Platelets ≥ 100 x 10^{9/L; Hemoglobin ≥ 9.0 g/dL; absolute neutrophil count (ANC) ≥ 1.5 x 10}9/L (without platelet transfusion or any growth factors within previous 7 days of the hematologic laboratory values obtained at screening visit)

• Hepatic: Aspartate transaminase (AST) / Alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) (if liver metastases are present, ≤ 5 x ULN); Total or conjugated bilirubin ≤ 1.5 x ULN

• Renal: Serum Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min as calculated by the Cockroft-Gault method

• Coagulation: International Normalized Ratio (INR) ≤ 1.2

Key Exclusion Criteria:

• Known brain metastasis or leptomeningeal disease

• Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of Cycle 1 Day 1

• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of alobresib, including any unresolved nausea, vomiting, or diarrhea that is Common Terminology Criteria for Adverse Events (CTCAE) Grade > 1

• Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy) within 21 days or 5 half-lives, whichever is longer, of study drug dosing (6 weeks for nitrosoureas, mitomycin C, or molecular agents with t1/2 > 10 days); concurrent use of an luteinizing hormone releasing hormone (LHRH) agonist is permitted for all individuals and ongoing enzalutamide is required in Group 3.

• History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (> 450 ms).

• Prior exposure to bromodomain (BET) inhibitors

• Clinically significant bleeding within 28 days of Cycle 1 Day 1

• Known human immunodeficiency virus (HIV) infection

• Hepatitis B surface antigen (HBsAg) positive

• Hepatitis C virus (HCV) antibody positive

• Use of moderate/strong cytochrome P450 (CYP)3A4 inhibitors or moderate/strong CYP3A4 inducers within 2 weeks prior to the first dose of study drug (with the exception of enzalutamide in the combination arms)

• Evidence of bleeding diathesis

• History of hemoptysis of ≥ 2.5 mL/1 teaspoon within 6 months of Cycle 1 Day 1

• History of high grade esophageal or gastric varices

• Anticoagulation/antiplatelet therapy within 7 days of Cycle 1 Day 1, including low molecular weight heparin, or warfarin.

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		San Francisco	California	United States	94158
2		Baltimore	Maryland	United States	21231
3		Boston	Massachusetts	United States	02114
4		Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol - Jun 30, 2016
• Statistical Analysis Plan - Nov 21, 2019

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02607228
• Other Study ID Numbers: GS-US-350-1604; 2015-003741-26
• First Posted: Nov 17, 2015
• Last Update Posted: Dec 8, 2020
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at 4 study sites in the United States. The first participant was screened on 08 December 2015. The last study visit occurred on 03 September 2019. Phase 2 Dose Expansion of the study was not conducted. Results are reported for only Dose Escalation Monotherapy and Combination Therapy.
Pre-assignment Detail	43 participants were screened.

Arm/Group Title	Monotherapy: Alobresib 2 mg	Monotherapy: Alobresib 3 mg	Monotherapy: Alobresib 4 mg	Monotherapy: Alobresib 6 mg	Monotherapy: Alobresib 9 mg	Combination Therapy: Alobresib 3 mg + Enzalutamide	Combination Therapy: Alobresib 6 mg + Enzalutamide
Arm/Group Description	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Period Title: Overall Study
STARTED	5	4	3	6	5	6	2
COMPLETED	0	0	0	0	0	0	0
NOT COMPLETED	5	4	3	6	5	6	2

Baseline Characteristics

Arm/Group Title	Monotherapy: Alobresib 2 mg	Monotherapy: Alobresib 3 mg	Monotherapy: Alobresib 4 mg	Monotherapy: Alobresib 6 mg	Monotherapy: Alobresib 9 mg	Combination Therapy: Alobresib 3 mg + Enzalutamide	Combination Therapy: Alobresib 6 mg + Enzalutamide	Total
Arm/Group Description	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Total of all reporting groups
Overall Participants	5	4	3	6	5	6	2	31
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.2 (9.28)	67.3 (10.69)	67.7 (5.69)	66.8 (9.39)	69.2 (6.61)	62.5 (10.23)	67.0 (0.00)	66.7 (8.25)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	5 100%	4 100%	3 100%	6 100%	5 100%	6 100%	2 100%	31 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	1 20%	1 16.7%	0 0%	2 6.5%
Not Hispanic or Latino	5 100%	4 100%	3 100%	6 100%	3 60%	5 83.3%	2 100%	28 90.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	1 20%	0 0%	0 0%	1 3.2%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	1 20%	0 0%	1 33.3%	0 0%	0 0%	1 16.7%	0 0%	3 9.7%
White	4 80%	4 100%	2 66.7%	6 100%	4 80%	5 83.3%	2 100%	27 87.1%
Other	0 0%	0 0%	0 0%	0 0%	1 20%	0 0%	0 0%	1 3.2%
Region of Enrollment (Count of Participants)
United States	5 100%	4 100%	3 100%	6 100%	5 100%	6 100%	2 100%	31 100%

Outcome Measures

1. Primary Outcome

Title	Phase 1b Dose Escalation: Number of Participants Experienced Dose Limiting Toxicities (DLTs)
Description	A DLT was a toxicity, considered possibly related to alobresib, and which occurred during the DLT assessment window (Days 1 through 28) in each cohort: Grade ≥ 4 neutropenia (absolute neutrophil count (ANC) < 500/mm^3), Grade ≥ 3 neutropenia (ANC< 1000/mm^3) with fever (a single temperature > 38.3°C or a sustained temperature of ≥ 38°C for more than 1 hour (h)), Grade ≥ 3 thrombocytopenia, Grade ≥ 2 bleeding (eg, gastrointestinal, respiratory, epistaxis, purpura), Grade ≥ 3 non hematologic toxicity, except- Grade 3 nausea or emesis with maximum duration of 48 h on adequate medical therapy and Grade 3 diarrhea which persists for < 72 h in the absence of maximal medical therapy, Grade ≥ 2 non hematologic treatment emergent adverse event (TEAE) that in the opinion of the investigator was of potential clinical significance such that further dose escalation would expose participants to unacceptable risk, treatment interruption ≥ 7 days due to unresolved toxicity.
Time Frame	Day 1 through Day 28

Outcome Measure Data

Analysis Population Description

The DLT Analysis Set included all participants in the Safety Analysis Set who completed all treatment and safety procedures through Day 28, inclusive, or experienced a DLT prior to Day 28, exclusive.

Arm/Group Title	Monotherapy: Alobresib 2 mg	Monotherapy: Alobresib 3 mg	Monotherapy: Alobresib 4 mg	Monotherapy: Alobresib 6 mg	Monotherapy: Alobresib 9 mg	Combination Therapy: Alobresib 3 mg + Enzalutamide	Combination Therapy: Alobresib 6 mg + Enzalutamide
Arm/Group Description	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Measure Participants	5	4	3	6	5	6	2
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%

2. Primary Outcome

Title	Phase 2 Dose Expansion: Non-progression Rate at Week 24 According to Prostate Cancer Working Group (PCWG2) Criteria
Description	The non-progression rate at Week 24 was defined as the proportion of participants who did not progress by Week 24.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The Phase 2 Dose Expansion of the study was not conducted.

Arm/Group Title	Monotherapy: Alobresib 2 mg	Monotherapy: Alobresib 3 mg	Monotherapy: Alobresib 4 mg	Monotherapy: Alobresib 6 mg	Monotherapy: Alobresib 9 mg	Combination Therapy: Alobresib 3 mg + Enzalutamide	Combination Therapy: Alobresib 6 mg + Enzalutamide
Arm/Group Description	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Measure Participants	0	0	0	0	0	0	0

3. Secondary Outcome

Title	Phase 1b Dose Escalation: Cmax: Maximum Observed Plasma Concentration of Alobresib
Description	Cmax is the maximum observed concentration of drug in plasma.
Time Frame	Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Days 1 and 15

Outcome Measure Data

Analysis Population Description

The PK Analysis Set included participants who took at least 1 dose of study drug and have at least 1 non-missing postdose concentration value. Participants with available data were analyzed. Monotherapy: Samples were not collected at Cycle 1 Day 1 and Cycle 1 Day 15; samples were only collected for participants who received alobresib 3 mg, 6 mg and 9 mg doses at Cycle 2 Day 1. Combination Therapy: Samples were not collected at Cycle 1 Day 8 and Cycle 2 Day 1.

Arm/Group Title	Monotherapy: Alobresib 2 mg	Monotherapy: Alobresib 3 mg	Monotherapy: Alobresib 4 mg	Monotherapy: Alobresib 6 mg	Monotherapy: Alobresib 9 mg	Combination Therapy: Alobresib 3 mg + Enzalutamide	Combination Therapy: Alobresib 6 mg + Enzalutamide
Arm/Group Description	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Measure Participants	5	4	3	6	5	6	2
Cycle 1 Day 1	111.07 (37.957)	199.00 (9.899)
Cycle 1 Day 8	263.00 (141.875)	263.75 (132.011)	367.33 (49.359)	293.33 (123.362)	526.00 (280.391)
Cycle 1 Day 15	84.4 (48.58)	173.5 (28.99)
Cycle 2 Day 1	220.50 (95.459)	203.50 (143.543)	641.00 (NA)

4. Secondary Outcome

Title	Phase 1b Dose Escalation: Ctau: Observed Drug Concentration at the End of the Dosing Interval of Alobresib
Description	Ctau is the observed concentration of drug in plasma at the end of dosing.
Time Frame	Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 15

Outcome Measure Data

Analysis Population Description

Participants in the PK Analysis Set with available data were analyzed. Monotherapy: Samples were not collected at Cycle 1 Day 15; samples were only collected for participants who received alobresib 3 mg, 6 mg and 9 mg doses at Cycle 2 Day 1. Combination Therapy: Samples were not collected at Cycle 1 Day 8 and Cycle 2 Day 1.

Arm/Group Title	Monotherapy: Alobresib 2 mg	Monotherapy: Alobresib 3 mg	Monotherapy: Alobresib 4 mg	Monotherapy: Alobresib 6 mg	Monotherapy: Alobresib 9 mg	Combination Therapy: Alobresib 3 mg + Enzalutamide	Combination Therapy: Alobresib 6 mg + Enzalutamide
Arm/Group Description	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Measure Participants	5	4	3	6	5	6	2
Cycle 1 Day 8	180.00 (77.679)	156.78 (100.307)	141.67 (22.811)	70.93 (32.905)	157.20 (126.996)
Cycle 1 Day 15	8.8 (7.77)	3.9 (3.21)
Cycle 2 Day 1	127.60 (59.963)	33.80 (NA)	268.00 (NA)

5. Secondary Outcome

Title	Phase 1b Dose Escalation: AUClast: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration of Alobresib
Description	AUClast is the concentration of drug over time zero to last concentration (area under the plasma concentration versus time curve).
Time Frame	Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Days 1 and 15

Outcome Measure Data

Analysis Population Description

Participants in the PK Analysis Set with available data were analyzed. Monotherapy: Samples were not collected at Cycle 1 Day 1 and Cycle 1 Day 15; samples were only collected for participants who received alobresib 3 mg, 6 mg and 9 mg doses at Cycle 2 Day 1. Combination Therapy: Samples were not collected at Cycle 1 Day 8 and Cycle 2 Day 1.

Arm/Group Title	Monotherapy: Alobresib 2 mg	Monotherapy: Alobresib 3 mg	Monotherapy: Alobresib 4 mg	Monotherapy: Alobresib 6 mg	Monotherapy: Alobresib 9 mg	Combination Therapy: Alobresib 3 mg + Enzalutamide	Combination Therapy: Alobresib 6 mg + Enzalutamide
Arm/Group Description	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Measure Participants	5	4	3	6	5	6	2
Cycle 1 Day 1	1026.99 (359.220)	1741.42 (737.521)
Cycle 1 Day 8	4207.55 (2319.854)	3742.30 (2106.308)	4646.08 (890.441)	3105.70 (1008.730)	4494.79 (4124.948)
Cycle 1 Day 15	652.7 (395.52)	701.3 (353.25)
Cycle 2 Day 1	3264.79 (2024.141)	1709.71 (264.402)	10264.74 (NA)

6. Secondary Outcome

Title	Phase 1b Dose Escalation: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Alobresib
Description	AUCtau is defined as the concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time Frame	Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 15

Outcome Measure Data

Analysis Population Description

Participants in the PK Analysis Set with available data were analyzed. Monotherapy: Samples were not collected at Cycle 1 Day 15; samples were only collected for participants who received alobresib 3 mg, 6 mg and 9 mg doses at Cycle 2 Day 1. Combination Therapy: Samples were not collected at Cycle 1 Day 8 and Cycle 2 Day 1.

Arm/Group Title	Monotherapy: Alobresib 2 mg	Monotherapy: Alobresib 3 mg	Monotherapy: Alobresib 4 mg	Monotherapy: Alobresib 6 mg	Monotherapy: Alobresib 9 mg	Combination Therapy: Alobresib 3 mg + Enzalutamide	Combination Therapy: Alobresib 6 mg + Enzalutamide
Arm/Group Description	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Measure Participants	5	4	3	6	5	6	2
Cycle 1 Day 8	4264.51 (2384.628)	3758.92 (2076.013)	4655.48 (949.099)	3128.58 (998.059)	7217.02 (4559.957)
Cycle 1 Day 15	765.3 (373.39)	701.3 (353.25)
Cycle 2 Day 1	3243.01 (2110.324)	1522.75 (NA)	10264.74 (NA)

7. Secondary Outcome

Title	Phase 1b Dose Escalation: Tmax: Time (Observed Time Point) of Cmax of Alobresib
Description	Tmax is the time observed for the Cmax of alobresib.
Time Frame	Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Days 1 and 15

Outcome Measure Data

Analysis Population Description

Participants in the PK Analysis Set with available data were analyzed. Monotherapy: Samples were not collected at Cycle 1 Day 1 and Cycle 1 Day 15; samples were only collected for participants who received alobresib 3 mg, 6 mg and 9 mg doses at Cycle 2 Day 1. Combination Therapy: Samples were not collected at Cycle 1 Day 8 and Cycle 2 Day 1.

Arm/Group Title	Monotherapy: Alobresib 2 mg	Monotherapy: Alobresib 3 mg	Monotherapy: Alobresib 4 mg	Monotherapy: Alobresib 6 mg	Monotherapy: Alobresib 9 mg	Combination Therapy: Alobresib 3 mg + Enzalutamide	Combination Therapy: Alobresib 6 mg + Enzalutamide
Arm/Group Description	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Measure Participants	5	4	3	6	5	6	2
Cycle 1 Day 1	1.07	0.46
Cycle 1 Day 8	0.50	0.66	0.58	1.42	0.72
Cycle 1 Day 15	0.5	0.5
Cycle 2 Day 1	1.76	4.93	4.08

8. Secondary Outcome

Title	Percentage of Participants Who Had ≥ 30% Reduction in Prostate Specific Antigen (PSA) From Baseline at Week 12
Description	PSA response was defined as percentage of participants with ≥ 30% decline in PSA from baseline by 12 weeks.
Time Frame	Baseline; Week 12

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	Monotherapy: Alobresib 2 mg	Monotherapy: Alobresib 3 mg	Monotherapy: Alobresib 4 mg	Monotherapy: Alobresib 6 mg	Monotherapy: Alobresib 9 mg	Combination Therapy: Alobresib 3 mg + Enzalutamide	Combination Therapy: Alobresib 6 mg + Enzalutamide
Arm/Group Description	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Measure Participants	5	4	3	6	5	6	2
Number [percentage of participants]	0.0 0%	0.0 0%	33.3 1110%	0.0 0%	0.0 0%	0.0 0%	0.0 0%

9. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS was defined as the interval from first dose date of study drug to the earlier of the first documentation of definitive disease progression (assessed per PCWG2) or death from any cause. PCWG2 criteria for progression was determined as 'Decline from baseline' when record start of therapy to first prostate-specific antigen (PSA) increase that is ≥ 25% and ≥ 2 ng/mL above the nadir and confirmed by a second value 3 or more weeks later; 'No decline from baseline' when PSA progression ≥ 25% and ≥ 2 ng/mL after 12 weeks.
Time Frame	Up to approximately 4 years

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	Monotherapy: Alobresib 2 mg	Monotherapy: Alobresib 3 mg	Monotherapy: Alobresib 4 mg	Monotherapy: Alobresib 6 mg	Monotherapy: Alobresib 9 mg	Combination Therapy: Alobresib 3 mg + Enzalutamide	Combination Therapy: Alobresib 6 mg + Enzalutamide
Arm/Group Description	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Measure Participants	4	3	2	6	4	5	1
Median (95% Confidence Interval) [months]	2.61	2.10	4.17	2.78	2.69	3.25	5.98

10. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is defined as the interval from first dose date of study drug to death from any cause.
Time Frame	Up to approximately 4 years

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	Monotherapy: Alobresib 2 mg	Monotherapy: Alobresib 3 mg	Monotherapy: Alobresib 4 mg	Monotherapy: Alobresib 6 mg	Monotherapy: Alobresib 9 mg	Combination Therapy: Alobresib 3 mg + Enzalutamide	Combination Therapy: Alobresib 6 mg + Enzalutamide
Arm/Group Description	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Measure Participants	5	4	3	6	5	6	2
Median (95% Confidence Interval) [months]	NA	NA	NA	NA	NA	NA	NA

Adverse Events

Time Frame	Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years
Adverse Event Reporting Description	The Safety Analysis Set included all participants who received >= 1 dose of study treatment with treatment group designated according to actual treatment.
Arm/Group Title	Monotherapy: Alobresib 2 mg		Monotherapy: Alobresib 3 mg		Monotherapy: Alobresib 4 mg		Monotherapy: Alobresib 6 mg		Monotherapy: Alobresib 9 mg		Combination Therapy: Alobresib 3 mg + Enzalutamide		Combination Therapy: Alobresib 6 mg + Enzalutamide
Arm/Group Description	Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).		Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.		Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.		Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.		Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.		Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.		Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
All Cause Mortality
	Monotherapy: Alobresib 2 mg		Monotherapy: Alobresib 3 mg		Monotherapy: Alobresib 4 mg		Monotherapy: Alobresib 6 mg		Monotherapy: Alobresib 9 mg		Combination Therapy: Alobresib 3 mg + Enzalutamide		Combination Therapy: Alobresib 6 mg + Enzalutamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Serious Adverse Events
	Monotherapy: Alobresib 2 mg		Monotherapy: Alobresib 3 mg		Monotherapy: Alobresib 4 mg		Monotherapy: Alobresib 6 mg		Monotherapy: Alobresib 9 mg		Combination Therapy: Alobresib 3 mg + Enzalutamide		Combination Therapy: Alobresib 6 mg + Enzalutamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		0/4 (0%)		1/3 (33.3%)		1/6 (16.7%)		2/5 (40%)		2/6 (33.3%)		1/2 (50%)
Eye disorders
Retinal detachment	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/5 (0%)		0/4 (0%)		1/3 (33.3%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Diverticular perforation	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
General disorders
Asthenia	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Fatigue	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Pyrexia	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Infections and infestations
Urinary tract infection	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		1/2 (50%)
Injury, poisoning and procedural complications
Fall	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Nervous system disorders
Central nervous system lesion	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Cerebrovascular accident	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Embolic stroke	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Renal and urinary disorders
Acute kidney injury	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Reproductive system and breast disorders
Pelvic pain	0/5 (0%)		0/4 (0%)		1/3 (33.3%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax	0/5 (0%)		0/4 (0%)		0/3 (0%)		1/6 (16.7%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Monotherapy: Alobresib 2 mg		Monotherapy: Alobresib 3 mg		Monotherapy: Alobresib 4 mg		Monotherapy: Alobresib 6 mg		Monotherapy: Alobresib 9 mg		Combination Therapy: Alobresib 3 mg + Enzalutamide		Combination Therapy: Alobresib 6 mg + Enzalutamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		3/4 (75%)		3/3 (100%)		6/6 (100%)		5/5 (100%)		5/6 (83.3%)		2/2 (100%)
Blood and lymphatic system disorders
Anaemia	2/5 (40%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		1/6 (16.7%)		0/2 (0%)
Thrombocytopenia	0/5 (0%)		0/4 (0%)		0/3 (0%)		1/6 (16.7%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Ear and labyrinth disorders
Ear pruritus	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Gastrointestinal disorders
Abdominal distension	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Abdominal pain	0/5 (0%)		1/4 (25%)		0/3 (0%)		1/6 (16.7%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Abdominal pain upper	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Constipation	2/5 (40%)		0/4 (0%)		1/3 (33.3%)		0/6 (0%)		1/5 (20%)		1/6 (16.7%)		0/2 (0%)
Diarrhoea	1/5 (20%)		1/4 (25%)		1/3 (33.3%)		3/6 (50%)		2/5 (40%)		1/6 (16.7%)		1/2 (50%)
Dry mouth	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Dysphagia	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Eructation	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Gastrooesophageal reflux disease	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Nausea	1/5 (20%)		1/4 (25%)		0/3 (0%)		1/6 (16.7%)		3/5 (60%)		0/6 (0%)		0/2 (0%)
Stomatitis	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Vomiting	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
General disorders
Asthenia	2/5 (40%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Catheter site extravasation	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Chest pain	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Chills	0/5 (0%)		0/4 (0%)		1/3 (33.3%)		1/6 (16.7%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Device related thrombosis	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Early satiety	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Fatigue	2/5 (40%)		0/4 (0%)		3/3 (100%)		3/6 (50%)		4/5 (80%)		2/6 (33.3%)		1/2 (50%)
Feeling cold	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Gait disturbance	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Influenza like illness	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		1/6 (16.7%)		0/2 (0%)
Non-cardiac chest pain	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		1/2 (50%)
Oedema peripheral	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Pain	1/5 (20%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		1/2 (50%)
Infections and infestations
Abdominal infection	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Herpes zoster	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Kidney infection	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Oral candidiasis	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Tooth infection	0/5 (0%)		0/4 (0%)		1/3 (33.3%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Viral infection	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Injury, poisoning and procedural complications
Contusion	0/5 (0%)		0/4 (0%)		0/3 (0%)		1/6 (16.7%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Fall	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Iliotibial band syndrome	0/5 (0%)		0/4 (0%)		0/3 (0%)		1/6 (16.7%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Joint injury	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Muscle strain	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Skin abrasion	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Upper limb fracture	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Wound haemorrhage	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Investigations
Aspartate aminotransferase increased	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Blood bilirubin increased	0/5 (0%)		1/4 (25%)		0/3 (0%)		1/6 (16.7%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Blood creatinine increased	1/5 (20%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Platelet count decreased	0/5 (0%)		1/4 (25%)		1/3 (33.3%)		0/6 (0%)		2/5 (40%)		0/6 (0%)		0/2 (0%)
Weight decreased	1/5 (20%)		0/4 (0%)		1/3 (33.3%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/5 (20%)		0/4 (0%)		0/3 (0%)		1/6 (16.7%)		4/5 (80%)		1/6 (16.7%)		0/2 (0%)
Dehydration	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Hyperglycaemia	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		2/5 (40%)		0/6 (0%)		0/2 (0%)
Hyperkalaemia	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Hypocalcaemia	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/5 (20%)		0/4 (0%)		1/3 (33.3%)		0/6 (0%)		1/5 (20%)		1/6 (16.7%)		0/2 (0%)
Arthritis	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Back pain	0/5 (0%)		0/4 (0%)		2/3 (66.7%)		2/6 (33.3%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Flank pain	1/5 (20%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Groin pain	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Joint swelling	1/5 (20%)		1/4 (25%)		0/3 (0%)		1/6 (16.7%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Muscle spasms	0/5 (0%)		0/4 (0%)		1/3 (33.3%)		3/6 (50%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Musculoskeletal pain	1/5 (20%)		0/4 (0%)		0/3 (0%)		1/6 (16.7%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Musculoskeletal stiffness	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Myalgia	0/5 (0%)		0/4 (0%)		0/3 (0%)		1/6 (16.7%)		1/5 (20%)		1/6 (16.7%)		0/2 (0%)
Neck pain	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Pathological fracture	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Nervous system disorders
Burning sensation	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Cognitive disorder	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Dysgeusia	0/5 (0%)		0/4 (0%)		1/3 (33.3%)		1/6 (16.7%)		0/5 (0%)		1/6 (16.7%)		1/2 (50%)
Headache	0/5 (0%)		0/4 (0%)		0/3 (0%)		1/6 (16.7%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Hemiparesis	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Memory impairment	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		1/2 (50%)
Neuropathy peripheral	1/5 (20%)		0/4 (0%)		0/3 (0%)		1/6 (16.7%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Paraesthesia	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Peripheral sensory neuropathy	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Psychiatric disorders
Abnormal dreams	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Anxiety	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Confusional state	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Depression	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Renal and urinary disorders
Acute kidney injury	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Dysuria	0/5 (0%)		1/4 (25%)		0/3 (0%)		1/6 (16.7%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Haematuria	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Pollakiuria	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Renal pain	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		1/2 (50%)
Urinary retention	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Urinary tract disorder	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Urinary tract obstruction	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Reproductive system and breast disorders
Erectile dysfunction	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Pelvic pain	0/5 (0%)		0/4 (0%)		0/3 (0%)		1/6 (16.7%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Dyspnoea	0/5 (0%)		0/4 (0%)		0/3 (0%)		1/6 (16.7%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Dyspnoea exertional	0/5 (0%)		0/4 (0%)		1/3 (33.3%)		1/6 (16.7%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Epistaxis	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Pulmonary embolism	1/5 (20%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Skin and subcutaneous tissue disorders
Dry skin	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Erythema	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Pain of skin	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		1/6 (16.7%)		0/2 (0%)
Rash	0/5 (0%)		0/4 (0%)		0/3 (0%)		2/6 (33.3%)		1/5 (20%)		0/6 (0%)		0/2 (0%)
Vascular disorders
Deep vein thrombosis	0/5 (0%)		1/4 (25%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Hot flush	1/5 (20%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Hypertension	0/5 (0%)		0/4 (0%)		0/3 (0%)		1/6 (16.7%)		0/5 (0%)		0/6 (0%)		0/2 (0%)
Hypotension	0/5 (0%)		0/4 (0%)		0/3 (0%)		0/6 (0%)		1/5 (20%)		0/6 (0%)		0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years.