TerminatedNCT02607228Updated Dec 8, 2020Results posted

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

A Phase 1/2 interventional study of Alobresib and Enzalutamide in Metastatic Castrate-Resistant Prostate Cancer, sponsored by Gilead Sciences. Terminated at 4 sites in United States. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-12-08.

Sponsored by Gilead Sciences · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 31
Allocation: Non-randomized
Ages: 18 Years and older
Sex: Male

Study 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)

Conditions studied

Metastatic Castrate-Resistant Prostate Cancer

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Prostatic Neoplasms 6,367

In context

Prostatic Neoplasms

6,367 studies on the registry are indexed under Prostatic Neoplasms; 1,397 are open to participants now.

This study's enrollment of 31 is below the median of 58 across 4,821 interventional studies indexed under Prostatic Neoplasms.

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Lead sponsor

Gilead Sciences is the lead sponsor of 680 studies on the registry; 24 are open to participants now.

Of its 259 completed or terminated interventional studies of FDA-regulated products, 249 (96%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Male
Accepts healthy volunteers: No

Eligibility criteria

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.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 31 participants (actual)

Study arms

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
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 · Drug: Enzalutamide
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
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 · Drug: Enzalutamide
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 · Drug: Enzalutamide

Interventions

DrugAlobresib
Tablet administered orally once daily.
Also known as: GS-5829
DrugEnzalutamide
Capsules administered orally once daily.
Also known as: XTANDI®

What researchers measure

Primary outcomes

Phase 1b Dose Escalation: Number of Participants Experienced Dose Limiting Toxicities (DLTs)
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
Phase 2 Dose Expansion: Non-progression Rate at Week 24 According to Prostate Cancer Working Group (PCWG2) Criteria
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

Secondary outcomes

Phase 1b Dose Escalation: Cmax: Maximum Observed Plasma Concentration of Alobresib
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
Phase 1b Dose Escalation: Ctau: Observed Drug Concentration at the End of the Dosing Interval of Alobresib
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
Phase 1b Dose Escalation: AUClast: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration of Alobresib
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
Phase 1b Dose Escalation: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Alobresib
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
Phase 1b Dose Escalation: Tmax: Time (Observed Time Point) of Cmax of Alobresib
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
Percentage of Participants Who Had ≥ 30% Reduction in Prostate Specific Antigen (PSA) From Baseline at Week 12
PSA response was defined as percentage of participants with ≥ 30% decline in PSA from baseline by 12 weeks.
Time frame: Baseline; Week 12
Progression Free Survival (PFS)
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
Overall Survival (OS)
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

Results

Posted Dec 8, 2020

Participant flow

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.

Participant flow — Overall Study
Milestone	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
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
Withdrew: Progressive disease	4	3	1	5	4	3	1
Withdrew: Adverse event	1	0	1	0	1	1	1
Withdrew: Investigator's discretion	0	0	1	0	0	1	0
Withdrew: Withdrew consent	0	1	0	0	0	1	0
Withdrew: Study terminated by sponsor	0	0	0	1	0	0	0

Outcome measures

PrimaryPhase 1b Dose Escalation: Number of Participants Experienced Dose Limiting Toxicities (DLTs)

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
Reported as:: Count of participants · Participants

Phase 1b Dose Escalation: Number of Participants Experienced Dose Limiting Toxicities (DLTs)
Participants	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
Phase 1b Dose Escalation: Number of Participants Experienced Dose Limiting Toxicities (DLTs)	0	0	0	0	0	1	0

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

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

No measurements were reported for this outcome.

SecondaryPhase 1b Dose Escalation: Cmax: Maximum Observed Plasma Concentration of Alobresib

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
Reported as:: Mean · ng/mL

Phase 1b Dose Escalation: Cmax: Maximum Observed Plasma Concentration of Alobresib
ng/mL	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
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	—	—

SecondaryPhase 1b Dose Escalation: Ctau: Observed Drug Concentration at the End of the Dosing Interval of Alobresib

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
Reported as:: Mean · ng/mL

Phase 1b Dose Escalation: Ctau: Observed Drug Concentration at the End of the Dosing Interval of Alobresib
ng/mL	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
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	—	—

SecondaryPhase 1b Dose Escalation: AUClast: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration of Alobresib

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
Reported as:: Mean · h*ng/mL

Phase 1b Dose Escalation: AUClast: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration of Alobresib
h*ng/mL	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
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	—	—

SecondaryPhase 1b Dose Escalation: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Alobresib

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
Reported as:: Mean · h*ng/mL

Phase 1b Dose Escalation: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Alobresib
h*ng/mL	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
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	—	—

SecondaryPhase 1b Dose Escalation: Tmax: Time (Observed Time Point) of Cmax of Alobresib

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
Reported as:: Median · hours

Phase 1b Dose Escalation: Tmax: Time (Observed Time Point) of Cmax of Alobresib
hours	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
Cycle 1 Day 1	—	—	—	—	—	1.07 (0.50 to 2.92)	0.46 (0.42 to 0.50)
Cycle 1 Day 8	0.50 (0.48 to 23.85)	0.66 (0.50 to 1.05)	0.58 (0.50 to 2.00)	1.42 (0.50 to 3.97)	0.72 (0.50 to 2.08)	—	—
Cycle 1 Day 15	—	—	—	—	—	0.5 (0.5 to 7.9)	0.5 (0.5 to 0.5)
Cycle 2 Day 1	—	1.76 (0.50 to 3.02)	—	4.93 (3.87 to 6.00)	4.08 (4.08 to 4.08)	—	—

SecondaryPercentage of Participants Who Had ≥ 30% Reduction in Prostate Specific Antigen (PSA) From Baseline at Week 12

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

Time frame:: Baseline; Week 12
Reported as:: Number · percentage of participants

Percentage of Participants Who Had ≥ 30% Reduction in Prostate Specific Antigen (PSA) From Baseline at Week 12
percentage of participants	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
Percentage of Participants Who Had ≥ 30% Reduction in Prostate Specific Antigen (PSA) From Baseline at Week 12	0.0	0.0	33.3	0.0	0.0	0.0	0.0

SecondaryProgression Free Survival (PFS)

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
Reported as:: Median · months

Progression Free Survival (PFS)
months	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
Progression Free Survival (PFS)	2.61 (1.58 to 8.61)	2.10 (1.97 to 2.60)	4.17 (2.79 to 5.55)	2.78 (2.69 to 11.07)	2.69 (0.53 to 14.00)	3.25 (1.15 to 21.59)	5.98 (NA to NA)

SecondaryOverall Survival (OS)

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
Reported as:: Median · months

Overall Survival (OS)
months	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
Overall Survival (OS)	NA (NA to NA)	NA (3.12 to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (1.15 to NA)	NA (NA to NA)

Adverse events

Collected over 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. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Monotherapy: Alobresib 2 mg	0/5 (0%)	2/5 (40%)	5/5 (100%)
Monotherapy: Alobresib 3 mg	1/4 (25%)	0/4 (0%)	3/4 (75%)
Monotherapy: Alobresib 4 mg	0/3 (0%)	1/3 (33.3%)	3/3 (100%)
Monotherapy: Alobresib 6 mg	0/6 (0%)	1/6 (16.7%)	6/6 (100%)
Monotherapy: Alobresib 9 mg	0/5 (0%)	2/5 (40%)	5/5 (100%)
Combination Therapy: Alobresib 3 mg + Enzalutamide	1/6 (16.7%)	2/6 (33.3%)	5/6 (83.3%)
Combination Therapy: Alobresib 6 mg + Enzalutamide	0/2 (0%)	1/2 (50%)	2/2 (100%)

Most frequent serious events

Showing 10 of 15

Most frequent serious events
Event	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
Urinary tract infectionInfections and infestations	0/5	0/4	0/3	0/6	0/5	0/6	1/2
Abdominal pain upperGastrointestinal disorders	0/5	0/4	1/3	0/6	0/5	0/6	0/2
Pelvic painReproductive system and breast disorders	0/5	0/4	1/3	0/6	0/5	0/6	0/2
Diverticular perforationGastrointestinal disorders	0/5	0/4	0/3	0/6	1/5	0/6	0/2
PyrexiaGeneral disorders	0/5	0/4	0/3	0/6	1/5	0/6	0/2
Back painMusculoskeletal and connective tissue disorders	1/5	0/4	0/3	0/6	0/5	0/6	0/2
Central nervous system lesionNervous system disorders	0/5	0/4	0/3	0/6	1/5	0/6	0/2
Cerebrovascular accidentNervous system disorders	0/5	0/4	0/3	0/6	1/5	0/6	0/2
Acute kidney injuryRenal and urinary disorders	1/5	0/4	0/3	0/6	0/5	0/6	0/2
Retinal detachmentEye disorders	0/5	0/4	0/3	0/6	0/5	1/6	0/2

Most frequent other events

Showing 10 of 100

Most frequent other events
Event	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
FatigueGeneral disorders	2/5	0/4	3/3	3/6	4/5	2/6	1/2
Decreased appetiteMetabolism and nutrition disorders	1/5	0/4	0/3	1/6	4/5	1/6	0/2
Back painMusculoskeletal and connective tissue disorders	0/5	0/4	2/3	2/6	1/5	0/6	0/2
NauseaGastrointestinal disorders	1/5	1/4	0/3	1/6	3/5	0/6	0/2
DiarrhoeaGastrointestinal disorders	1/5	1/4	1/3	3/6	2/5	1/6	1/2
Non-cardiac chest painGeneral disorders	0/5	0/4	0/3	0/6	1/5	0/6	1/2
PainGeneral disorders	1/5	1/4	0/3	0/6	1/5	0/6	1/2
Muscle spasmsMusculoskeletal and connective tissue disorders	0/5	0/4	1/3	3/6	0/5	0/6	0/2
DysgeusiaNervous system disorders	0/5	0/4	1/3	1/6	0/5	1/6	1/2
Memory impairmentNervous system disorders	0/5	0/4	0/3	0/6	0/5	0/6	1/2

Baseline characteristics

All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.

Age, Continuous
Age, Continuous(years)	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
Mean	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
Sex: Female, Male(Participants)	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
Female	0	0	0	0	0	0	0	0
Male	5	4	3	6	5	6	2	31

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	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
Hispanic or Latino	0	0	0	0	1	1	0	2
Not Hispanic or Latino	5	4	3	6	3	5	2	28
Unknown or Not Reported	0	0	0	0	1	0	0	1

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	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
Race — Black or African American	1	0	1	0	0	1	0	3
Race — White	4	4	2	6	4	5	2	27
Race — Other	0	0	0	0	1	0	0	1

Region of Enrollment
Region of Enrollment(Participants)	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
United States	5	4	3	6	5	6	2	31

Study locations

4 sites

San Francisco, California 94158, United States
Baltimore, Maryland 21231, United States
Boston, Massachusetts 02114, United States
Durham, North Carolina 27710, United States

References and documents

Study documents

Study protocol · Jun 30, 2016
Statistical analysis plan · Nov 21, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 8, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02607228
Lead sponsor: Gilead Sciences
Responsible party: Sponsor
First posted: Nov 17, 2015
Start date: Dec 8, 2015
Primary completion: Oct 25, 2017
Completion: Sep 3, 2019
Results posted: Dec 8, 2020
Last update: Dec 8, 2020

Study contacts

Gilead Study Director

study director · Gilead Sciences

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Dec 2020. You cannot join it, but the record below documents what was studied.

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