Trial Outcomes & Findings for Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 (Apalutamide) in Castration-Resistant Prostate Cancer (CRPC) (NCT NCT01171898)

Last Updated: 2025-11-12

Results Overview

Percentage of participants with \>=50% decrease in PSA compared to baseline were assessed at Week 12. PSA progression was defined by the protocol-specific Prostate Cancer Working Group 2 (PCWG2) criteria: PSA increase greater than or equal to \[\>=\] 25 percent \[%\] and \>=2 nanogram per milliliter \[ng/mL\] above the nadir confirmed \>=3 weeks later; or \>=25% and \>=2 ng/mL above baseline PSA after 12 weeks.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

127 participants

Primary outcome timeframe

Week 12

Results posted on

2025-11-12

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 2: Treatment-naive Metastatic CRPC (Phase 2) CRPC (Phase 2) Participants with metastatic CRPC who had not received chemotherapy for metastatic disease or prior abiraterone acetate (treatmentnaive) were enrolled in Cohort 2 of Phase 2, received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.	Dose Escalation Cohort (Phase 1) Participants received apalutamide (ARN-509) at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily (up to 240 mg once daily and at higher doses of 300/390/480 mg twice daily dosing). Once Recommended Phase 2 Dose (RP2D) was selected, Phase 1 participants being treated at the lower dose levels were allowed to escalate to the RP2D level (240 mg) at the discretion of the primary investigator.	Cohort 1: Non-metastatic CRPC (Phase 2) Participants with non-metastatic, treatment naive Castration-Resistant Prostate Cancer (CRPC) with rapidly rising Prostate Specific Antigen (PSA) enrolled in Cohort 1 of Phase 2, received apalutamide at Maximum Tolerated Dose (MTD) and/or RP2D of 240 mg, determined in Phase 1.	Cohort 3: Post-Abiraterone Metastatic CRPC (Phase 2) Participants with metastatic CRPC that were chemotherapynaive, but had been previously treated with abiraterone acetate enrolled in Cohort 3 of Phase 2 received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.
Overall Study STARTED	25	30	51	21
Overall Study COMPLETED	13	26	32	15
Overall Study NOT COMPLETED	12	4	19	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 2: Treatment-naive Metastatic CRPC (Phase 2) CRPC (Phase 2) Participants with metastatic CRPC who had not received chemotherapy for metastatic disease or prior abiraterone acetate (treatmentnaive) were enrolled in Cohort 2 of Phase 2, received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.	Dose Escalation Cohort (Phase 1) Participants received apalutamide (ARN-509) at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily (up to 240 mg once daily and at higher doses of 300/390/480 mg twice daily dosing). Once Recommended Phase 2 Dose (RP2D) was selected, Phase 1 participants being treated at the lower dose levels were allowed to escalate to the RP2D level (240 mg) at the discretion of the primary investigator.	Cohort 1: Non-metastatic CRPC (Phase 2) Participants with non-metastatic, treatment naive Castration-Resistant Prostate Cancer (CRPC) with rapidly rising Prostate Specific Antigen (PSA) enrolled in Cohort 1 of Phase 2, received apalutamide at Maximum Tolerated Dose (MTD) and/or RP2D of 240 mg, determined in Phase 1.	Cohort 3: Post-Abiraterone Metastatic CRPC (Phase 2) Participants with metastatic CRPC that were chemotherapynaive, but had been previously treated with abiraterone acetate enrolled in Cohort 3 of Phase 2 received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.
Overall Study Death	2	0	0	0
Overall Study Lost to Follow-up	1	0	1	1
Overall Study Withdrawal by Subject	6	1	4	3
Overall Study Terminated by Sponsor	0	1	0	0
Overall Study Ongoing	3	1	9	0
Overall Study Other	0	1	5	2

Baseline Characteristics

Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 (Apalutamide) in Castration-Resistant Prostate Cancer (CRPC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Escalation Cohort (Phase 1) n=30 Participants Participants received apalutamide at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily (up to 240 mg once daily and at higher doses of 300/390/480 mg twice daily dosing). Once Recommended Phase 2 Dose (RP2D) was selected, Phase 1 participants being treated at the lower dose levels were allowed to escalate to the RP2D level (240 mg) at the discretion of the primary investigator.	Cohort 1: Non-metastatic CRPC (Phase 2) n=51 Participants Participants with non-metastatic, treatment naive Castration-Resistant Prostate Cancer (CRPC) with rapidly rising Prostate Specific Antigen (PSA) enrolled in Cohort 1 of Phase 2, received apalutamide at Maximum Tolerated Dose (MTD) and/or RP2D of 240 mg, determined in Phase 1.	Cohort 2: Treatment-naive Metastatic CRPC (Phase 2) n=25 Participants CRPC (Phase 2) Participants with metastatic CRPC who had not received chemotherapy for metastatic disease or prior abiraterone acetate (treatmentnaive) were enrolled in Cohort 2 of Phase 2, received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.	Cohort 3: Post-Abiraterone Metastatic CRPC (Phase 2) n=21 Participants Participants with metastatic CRPC that were chemotherapynaive, but had been previously treated with abiraterone acetate enrolled in Cohort 3 of Phase 2 received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.	Total n=127 Participants Total of all reporting groups
Age, Continuous	67.7 years STANDARD_DEVIATION 9.44 • n=10 Participants	72.8 years STANDARD_DEVIATION 8.73 • n=10 Participants	70 years STANDARD_DEVIATION 11.8 • n=20 Participants	67.4 years STANDARD_DEVIATION 9.28 • n=45 Participants	70.2 years STANDARD_DEVIATION 9.82 • n=44 Participants
Sex: Female, Male Female	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	0 Participants n=44 Participants
Sex: Female, Male Male	30 Participants n=10 Participants	51 Participants n=10 Participants	25 Participants n=20 Participants	21 Participants n=45 Participants	127 Participants n=44 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=10 Participants	2 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	3 Participants n=44 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=10 Participants	49 Participants n=10 Participants	25 Participants n=20 Participants	21 Participants n=45 Participants	124 Participants n=44 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	0 Participants n=44 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	0 Participants n=44 Participants
Race (NIH/OMB) Asian	0 Participants n=10 Participants	1 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	1 Participants n=44 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	0 Participants n=44 Participants
Race (NIH/OMB) Black or African American	0 Participants n=10 Participants	3 Participants n=10 Participants	0 Participants n=20 Participants	2 Participants n=45 Participants	5 Participants n=44 Participants
Race (NIH/OMB) White	30 Participants n=10 Participants	47 Participants n=10 Participants	25 Participants n=20 Participants	19 Participants n=45 Participants	121 Participants n=44 Participants
Race (NIH/OMB) More than one race	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	0 Participants n=44 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	0 Participants n=44 Participants
Region of Enrollment United States	30 Participants n=10 Participants	51 Participants n=10 Participants	25 Participants n=20 Participants	21 Participants n=45 Participants	127 Participants n=44 Participants

PRIMARY outcome

Timeframe: Week 12

Population: Modified intent-to-treat (mITT) population included all participants who received at least one dose of apalutamide and who were eligible for the cohort that they were enrolled in.

Outcome measures

Outcome measures
Measure	Dose Escalation Cohort (Phase 1) n=30 Participants Participants received apalutamide at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily (up to 240 mg once daily and at higher doses of 300/390/480 mg twice daily dosing). Once Recommended Phase 2 Dose (RP2D) was selected, Phase 1 participants being treated at the lower dose levels were allowed to escalate to the RP2D level (240 mg) at the discretion of the primary investigator.	Cohort 1: Non-metastatic CRPC (Phase 2) n=47 Participants Participants with non-metastatic, treatment naive Castration-Resistant Prostate Cancer (CRPC) with rapidly rising Prostate Specific Antigen (PSA) enrolled in Cohort 1 of Phase 2, received apalutamide at Maximum Tolerated Dose (MTD) and/or RP2D of 240 mg, determined in Phase 1.	Cohort 2: Treatment-naive Metastatic CRPC (Phase 2) n=25 Participants Participants with metastatic CRPC who had not received chemotherapy for metastatic disease or prior abiraterone acetate (treatment-naive) were enrolled in Cohort 2 of Phase 2, received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.	Cohort 3: Post-Abiraterone Metastatic CRPC (Phase 2) n=18 Participants Participants with metastatic CRPC that were chemotherapy-naive, but had been previously treated with abiraterone acetate enrolled in Cohort 3 of Phase 2 received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.
Phase 1 and 2: Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) at Week 12	47 Percentage of Participants	89 Percentage of Participants	88 Percentage of Participants	22 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately 7 years

Population: mITT population included all participants who received at least one dose of apalutamide and who were eligible for the cohort that they were enrolled in.

Time to PSA progression was measured as the time interval from the date of the first dose to the date of PSA progression as defined by the PCWG2 criteria. PCWG2 criteria: For participants who achieved \>=50% decrease from the baseline PSA, assessment of time to disease progression was when the PSA increased 25% and at a minimum of 2 ng/mL above the nadir at 3 or more weeks later. For participants without a PSA decrease, the time for progression was calculated at the time when the PSA progression was \>=25% and \>=2 ng/mL after 12 weeks.

Outcome measures

Outcome measures
Measure	Dose Escalation Cohort (Phase 1) n=30 Participants Participants received apalutamide at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily (up to 240 mg once daily and at higher doses of 300/390/480 mg twice daily dosing). Once Recommended Phase 2 Dose (RP2D) was selected, Phase 1 participants being treated at the lower dose levels were allowed to escalate to the RP2D level (240 mg) at the discretion of the primary investigator.	Cohort 1: Non-metastatic CRPC (Phase 2) n=47 Participants Participants with non-metastatic, treatment naive Castration-Resistant Prostate Cancer (CRPC) with rapidly rising Prostate Specific Antigen (PSA) enrolled in Cohort 1 of Phase 2, received apalutamide at Maximum Tolerated Dose (MTD) and/or RP2D of 240 mg, determined in Phase 1.	Cohort 2: Treatment-naive Metastatic CRPC (Phase 2) n=25 Participants Participants with metastatic CRPC who had not received chemotherapy for metastatic disease or prior abiraterone acetate (treatment-naive) were enrolled in Cohort 2 of Phase 2, received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.	Cohort 3: Post-Abiraterone Metastatic CRPC (Phase 2) n=18 Participants Participants with metastatic CRPC that were chemotherapy-naive, but had been previously treated with abiraterone acetate enrolled in Cohort 3 of Phase 2 received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.
Phase 1 and 2: Median Time to PSA Progression	4.9 Months Interval 3.9 to 9.5	24.0 Months Interval 16.3 to 35.0	16.5 Months Interval 5.6 to 59.5	3.0 Months Interval 2.7 to 4.7

SECONDARY outcome

Timeframe: Up to approximately 7 years

Population: mITT population included all participants who received at least 1 dose of apalutamide and were eligible for cohort that they were enrolled in. MFS results are reported for Cohort 1 (Phase 2) participants only as MFS analysis was not performed for other cohorts that is Dose Escalation Cohort (Phase 1) and Cohort 2, 3 (Phase 2) per planned analysis.

MFS was defined as the time from the start of treatment until new metastatic lesions were observed on Computed Tomography/ Magnetic Resonance Imaging (CT/MRI) scans or radionuclide bone scans (according to PCWG2 criteria: appearance of \>=2 new lesions, and, for the first reassessment only, a confirmatory scan performed 6 or more weeks later that showed at least 2 or more additional new lesions) or death, whichever occurred first.

Outcome measures

Outcome measures
Measure	Dose Escalation Cohort (Phase 1) n=47 Participants Participants received apalutamide at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily (up to 240 mg once daily and at higher doses of 300/390/480 mg twice daily dosing). Once Recommended Phase 2 Dose (RP2D) was selected, Phase 1 participants being treated at the lower dose levels were allowed to escalate to the RP2D level (240 mg) at the discretion of the primary investigator.	Cohort 1: Non-metastatic CRPC (Phase 2) Participants with non-metastatic, treatment naive Castration-Resistant Prostate Cancer (CRPC) with rapidly rising Prostate Specific Antigen (PSA) enrolled in Cohort 1 of Phase 2, received apalutamide at Maximum Tolerated Dose (MTD) and/or RP2D of 240 mg, determined in Phase 1.	Cohort 2: Treatment-naive Metastatic CRPC (Phase 2) Participants with metastatic CRPC who had not received chemotherapy for metastatic disease or prior abiraterone acetate (treatment-naive) were enrolled in Cohort 2 of Phase 2, received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.	Cohort 3: Post-Abiraterone Metastatic CRPC (Phase 2) Participants with metastatic CRPC that were chemotherapy-naive, but had been previously treated with abiraterone acetate enrolled in Cohort 3 of Phase 2 received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.
Phase 2: Median Metastasis-Free Survival (MFS)	21.6 Months Interval 11.5 to 40.9	—	—	—

SECONDARY outcome

Timeframe: Up to approximately 7 years

Population: mITT population included all participants who received at least 1 dose of apalutamide and who were eligible for cohort that they were enrolled in. PFS results are reported for Dose Escalation Cohort (Phase 1) and cohort 2, 3 (Phase 2) as no PFS analysis was performed for Cohort 1 of Phase 2 per planned analysis.

PFS was defined as the time from randomization to the radiographic disease progression or death, whichever occurred first. Radiographic progression defined by at least one of the following: a) Soft tissue progression by modified RECIST confirmed on repeat imaging \>= 6 weeks later; b) Progression by bone scans: 1) first bone scan with \>= 2 new lesions compared to baseline observed \<12 weeks from start date and confirmed on a second bone scan \>=6 weeks later that showed \>=2 additional lesions (a total of \>=4 new lesions compared to baseline); or 2) first bone scan with \>=2 new lesions compared to baseline observed \>=12 weeks from start date and the new lesions verified on the next bone scan \>=6 weeks later (a total of \>=2 new lesions compared to baseline).

Outcome measures

Outcome measures
Measure	Dose Escalation Cohort (Phase 1) n=30 Participants Participants received apalutamide at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily (up to 240 mg once daily and at higher doses of 300/390/480 mg twice daily dosing). Once Recommended Phase 2 Dose (RP2D) was selected, Phase 1 participants being treated at the lower dose levels were allowed to escalate to the RP2D level (240 mg) at the discretion of the primary investigator.	Cohort 1: Non-metastatic CRPC (Phase 2) n=25 Participants Participants with non-metastatic, treatment naive Castration-Resistant Prostate Cancer (CRPC) with rapidly rising Prostate Specific Antigen (PSA) enrolled in Cohort 1 of Phase 2, received apalutamide at Maximum Tolerated Dose (MTD) and/or RP2D of 240 mg, determined in Phase 1.	Cohort 2: Treatment-naive Metastatic CRPC (Phase 2) n=18 Participants Participants with metastatic CRPC who had not received chemotherapy for metastatic disease or prior abiraterone acetate (treatment-naive) were enrolled in Cohort 2 of Phase 2, received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.	Cohort 3: Post-Abiraterone Metastatic CRPC (Phase 2) Participants with metastatic CRPC that were chemotherapy-naive, but had been previously treated with abiraterone acetate enrolled in Cohort 3 of Phase 2 received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.
Phase 1 and 2: Progression-free Survival (PFS)	16.82 Months Interval 11.76 to Here NA signifies that the upper limit of Confidence Interval (CI) was not estimable due to lesser number of events.	36.37 Months Interval 16.66 to Here NA signifies that the upper limit of Confidence Interval (CI) was not estimable due to lesser number of events.	NA Months Here NA signifies that the median, lower and upper limit of Confidence Interval (CI) were not estimable due to lesser number of events.	—

SECONDARY outcome

Timeframe: Up to approximately 7 years

Population: mITT population included all participants who received at least one dose of apalutamide and who were eligible for the cohort that they were enrolled in.

Objective Response Rate was defined as the percentage of participants with best overall response (OR) of confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.0 (RECIST). Where, CR defined as disappearance of all target lesions. Any pathological lymph nodes must had reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions. Confirmed responses were those that persisted on repeat imaging study for at least 4 weeks after initial documentation of response.

Outcome measures

Outcome measures
Measure	Dose Escalation Cohort (Phase 1) n=30 Participants Participants received apalutamide at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily (up to 240 mg once daily and at higher doses of 300/390/480 mg twice daily dosing). Once Recommended Phase 2 Dose (RP2D) was selected, Phase 1 participants being treated at the lower dose levels were allowed to escalate to the RP2D level (240 mg) at the discretion of the primary investigator.	Cohort 1: Non-metastatic CRPC (Phase 2) n=47 Participants Participants with non-metastatic, treatment naive Castration-Resistant Prostate Cancer (CRPC) with rapidly rising Prostate Specific Antigen (PSA) enrolled in Cohort 1 of Phase 2, received apalutamide at Maximum Tolerated Dose (MTD) and/or RP2D of 240 mg, determined in Phase 1.	Cohort 2: Treatment-naive Metastatic CRPC (Phase 2) n=25 Participants Participants with metastatic CRPC who had not received chemotherapy for metastatic disease or prior abiraterone acetate (treatment-naive) were enrolled in Cohort 2 of Phase 2, received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.	Cohort 3: Post-Abiraterone Metastatic CRPC (Phase 2) n=18 Participants Participants with metastatic CRPC that were chemotherapy-naive, but had been previously treated with abiraterone acetate enrolled in Cohort 3 of Phase 2 received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.
Phase 1 and 2: Objective Response Rate	20 Percentage of Participants Interval 2.52 to 55.61	0 Percentage of Participants Interval 0.0 to 97.5	50 Percentage of Participants Interval 15.7 to 84.3	0 Percentage of Participants Interval 0.0 to 30.85

Adverse Events

Dose Escalation Cohort (Phase 1)

Serious events: 7 serious events

Other events: 29 other events

Deaths: 0 deaths

Cohort 1: Non-metastatic CRPC (Phase 2)

Serious events: 16 serious events

Other events: 49 other events

Deaths: 0 deaths

Cohort 2: Treatment-naive Metastatic CRPC (Phase 2)

Serious events: 10 serious events

Other events: 25 other events

Deaths: 2 deaths

Cohort 3: Post-Abiraterone Metastatic CRPC (Phase 2)

Serious events: 6 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Medical Director, WC Clinical Oncology Department

Aragon Pharmaceuticals, Inc.

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER