Trial Outcomes & Findings for A Study of Apalutamide (Adjuvant Treatment) and Androgen Deprivation Therapy (ADT) in Participants Who Have Undergone Radical Prostatectomy (RP) for Non-metastatic Prostate Cancer and Who Are at High Risk for Metastases (NCT NCT04523207)

Last Updated: 2025-04-25

Results Overview

Confirmed BCR-free rate was estimated from primary efficacy variable, time to confirmed BCR. This was measured as the interval between the date of the first dose of study drug and the date of the first occurrence of confirmed prostate specific antigen (PSA) greater than (\>) 0.2 nanogram per milliliter (ng/mL). Confirmation of the PSA value was conducted within 3 to 4 weeks, regardless of study visit and timing. Participants without confirmed PSA \> 0.2 ng/mL (including those who were lost to follow-up) were censored on their last PSA measurement date during the treatment phase of the study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

108 participants

Primary outcome timeframe

At Month 24

Results posted on

2025-04-25

Participant Flow

Study consisted of main study (12 treatment cycles) and sub study (single treatment cycle). Each cycle was of 28 days. Unique participants were enrolled either into main or sub-study. Study treatment was initiated between Day 29 and 90 post radical prostatectomy. After sub-study completion and serum testosterone assessment (primary analysis) and safety (secondary analysis), participants were transitioned into main study from Cycle 2 Day 1 and continued treatment through Cycle 12 in main study.

Participant milestones

Participant milestones
Measure	Main Study: Apalutamide Plus Androgen Deprivation Therapy (ADT) In main study, participants received apalutamide 240 milligrams (mg; 4 tablets of 60 mg) orally once daily (QD) along with ADT intramuscular or subcutaneous injection from Cycle 1 Day 1 up to Cycle 12. Each cycle was of 28 days.	Sub Study: Relugolix Followed by Apalutamide Plus Relugolix In sub-study, participants received a loading dose of relugolix 360 mg (3 tablets of 120 mg) on Day -14 and then relugolix 120 mg orally QD up to Day 28 and accompanied by apalutamide 240 mg (4 tablets of 60 mg tablets) orally QD from Day 1 up to Day 28. Upon completion of 28-day sub-study, participants were transitioned into the main study from Cycle 2 Day 1 and continued to receive apalutamide with ADT (oral relugolix) through Cycle 12. Each cycle was of 28 days.
Overall Study STARTED	96	12
Overall Study Sub-study Participants Who Completed and Transitioned to Main Study	0	12
Overall Study COMPLETED	78	9
Overall Study NOT COMPLETED	18	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Main Study: Apalutamide Plus Androgen Deprivation Therapy (ADT) In main study, participants received apalutamide 240 milligrams (mg; 4 tablets of 60 mg) orally once daily (QD) along with ADT intramuscular or subcutaneous injection from Cycle 1 Day 1 up to Cycle 12. Each cycle was of 28 days.	Sub Study: Relugolix Followed by Apalutamide Plus Relugolix In sub-study, participants received a loading dose of relugolix 360 mg (3 tablets of 120 mg) on Day -14 and then relugolix 120 mg orally QD up to Day 28 and accompanied by apalutamide 240 mg (4 tablets of 60 mg tablets) orally QD from Day 1 up to Day 28. Upon completion of 28-day sub-study, participants were transitioned into the main study from Cycle 2 Day 1 and continued to receive apalutamide with ADT (oral relugolix) through Cycle 12. Each cycle was of 28 days.
Overall Study Adverse Event	5	1
Overall Study Lost to Follow-up	2	0
Overall Study Withdrawal by Subject	2	0
Overall Study Progressive Disease	2	1
Overall Study Other	7	1

Baseline Characteristics

A Study of Apalutamide (Adjuvant Treatment) and Androgen Deprivation Therapy (ADT) in Participants Who Have Undergone Radical Prostatectomy (RP) for Non-metastatic Prostate Cancer and Who Are at High Risk for Metastases

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Main Study: Apalutamide Plus Androgen Deprivation Therapy (ADT) n=96 Participants In main study, participants received apalutamide 240 milligrams (mg; 4 tablets of 60 mg) orally once daily (QD) along with ADT intramuscular or subcutaneous injection from Cycle 1 Day 1 up to Cycle 12. Each cycle was of 28 days.	Sub Study: Relugolix Followed by Apalutamide Plus Relugolix n=12 Participants In sub-study, participants received a loading dose of relugolix 360 mg (3 tablets of 120 mg) on Day -14 and then relugolix 120 mg orally QD up to Day 28 and accompanied by apalutamide 240 mg (4 tablets of 60 mg tablets) orally QD from Day 1 up to Day 28. Upon completion of 28-day sub-study, participants were transitioned into the main study from Cycle 2 Day 1 and continued to receive apalutamide with ADT (oral relugolix) through Cycle 12. Each cycle was of 28 days.	Total n=108 Participants Total of all reporting groups
Age, Continuous	65.2 years STANDARD_DEVIATION 7.33 • n=5 Participants	64.6 years STANDARD_DEVIATION 8.46 • n=7 Participants	65.2 years STANDARD_DEVIATION 7.42 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	96 Participants n=5 Participants	12 Participants n=7 Participants	108 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	87 Participants n=5 Participants	12 Participants n=7 Participants	99 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants	2 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	80 Participants n=5 Participants	8 Participants n=7 Participants	88 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment UNITED STATES	96 Participants n=5 Participants	12 Participants n=7 Participants	108 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Month 24

Population: Modified intent-to-treat (MITT) analysis set included all participants who were enrolled in the study, received at least 1 dose of apalutamide, and had a baseline prostate-specific antigen (PSA) and at least 1 post-treatment PSA assessment. Data for this outcome measures was planned to be collected and analyzed for combined population of main study and sub-study (after the participants transitioned into main study).

Outcome measures

Outcome measures
Measure	Apalutamide Plus ADT (Main Study) + Relugolix Followed by Apalutamide Plus Relugolix (Sub Study) n=108 Participants In main study, participants received apalutamide 240 milligrams (mg; 4 tablets of 60 mg) orally once daily (QD) along with ADT from Cycle 1 Day 1 up to Cycle 12. In sub-study, participants received a loading dose of relugolix 360 mg (3 tablets of 120 mg) on Day -14 and then relugolix 120 mg orally QD up to Day 28 and followed by apalutamide 240 mg (4 tablets of 60 mg tablets) orally QD from Day 1 up to Day 28. Upon completion of 28-day sub-study, participants were transitioned into the main study from Cycle 2 Day 1 and continued to receive apalutamide along with ADT (of investigator's choice) through Cycle 12. Each cycle was of 28 days.
Confirmed Biochemical Recurrence (BCR)-Free Rate at Month 24	100 Percentage of participants Interval 93.4 to 100.0

PRIMARY outcome

Timeframe: From Day -14 through Day 28

Population: MITT analysis set included all participants were enrolled in the study, received at least 1 dose of apalutamide, and had a baseline PSA and at least 1 post-treatment PSA assessment. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for main study.

Percentage of participants maintaining testosterone level \<50 ng/dL through Day 28 were reported.

Outcome measures

Outcome measures
Measure	Apalutamide Plus ADT (Main Study) + Relugolix Followed by Apalutamide Plus Relugolix (Sub Study) n=11 Participants In main study, participants received apalutamide 240 milligrams (mg; 4 tablets of 60 mg) orally once daily (QD) along with ADT from Cycle 1 Day 1 up to Cycle 12. In sub-study, participants received a loading dose of relugolix 360 mg (3 tablets of 120 mg) on Day -14 and then relugolix 120 mg orally QD up to Day 28 and followed by apalutamide 240 mg (4 tablets of 60 mg tablets) orally QD from Day 1 up to Day 28. Upon completion of 28-day sub-study, participants were transitioned into the main study from Cycle 2 Day 1 and continued to receive apalutamide along with ADT (of investigator's choice) through Cycle 12. Each cycle was of 28 days.
Sub-study: Percentage of Participants Who Maintained Testosterone Level Less Than (<) 50 Nanograms Per Deciliter (ng/dL) Through Day 28	100 Percentage of participants

SECONDARY outcome

Timeframe: At Month 12

Population: MITT analysis set included all participants were enrolled in the study, received at least 1 dose of apalutamide, and had a baseline PSA and at least 1 post-treatment PSA assessment. Data for this outcome measures was planned to be collected and analyzed for combined population of main study and sub-study (after the participants transitioned into main study).

Confirmed BCR-free rate was estimated from primary efficacy variable, time to confirmed BCR. This was measured as the interval between the date of the first dose of study drug and the date of the first occurrence of confirmed PSA \>0.2 ng/mL. Confirmation of the PSA value was conducted within 3 to 4 weeks, regardless of study visit and timing. Participants without confirmed PSA \> 0.2 ng/mL (including those who were lost to follow-up) were censored on their last PSA measurement date during the treatment phase of the study.

Outcome measures

Outcome measures
Measure	Apalutamide Plus ADT (Main Study) + Relugolix Followed by Apalutamide Plus Relugolix (Sub Study) n=108 Participants In main study, participants received apalutamide 240 milligrams (mg; 4 tablets of 60 mg) orally once daily (QD) along with ADT from Cycle 1 Day 1 up to Cycle 12. In sub-study, participants received a loading dose of relugolix 360 mg (3 tablets of 120 mg) on Day -14 and then relugolix 120 mg orally QD up to Day 28 and followed by apalutamide 240 mg (4 tablets of 60 mg tablets) orally QD from Day 1 up to Day 28. Upon completion of 28-day sub-study, participants were transitioned into the main study from Cycle 2 Day 1 and continued to receive apalutamide along with ADT (of investigator's choice) through Cycle 12. Each cycle was of 28 days.
Confirmed Biochemical Recurrence (BCR)-Free Rate at Month 12	100 Percentage of participants Interval 94.8 to 100.0

SECONDARY outcome

Timeframe: At Months 18 and 24

Population: MITT analysis set included all participants were enrolled in the study, received at least 1 dose of apalutamide, and had a baseline PSA and at least 1 post-treatment PSA assessment. Data for this outcome measures was planned to be collected and analyzed for combined population of main study and sub-study (after the participants transitioned into main study).

Percentage of participants with serum testosterone recovery (\>=150 ng/dL) at Months 18 and 24 were reported. Testosterone recovery was defined as a serum testosterone level greater than or equal to (\>=)150 nanograms per deciliter (ng/dL).

Outcome measures

Outcome measures
Measure	Apalutamide Plus ADT (Main Study) + Relugolix Followed by Apalutamide Plus Relugolix (Sub Study) n=108 Participants In main study, participants received apalutamide 240 milligrams (mg; 4 tablets of 60 mg) orally once daily (QD) along with ADT from Cycle 1 Day 1 up to Cycle 12. In sub-study, participants received a loading dose of relugolix 360 mg (3 tablets of 120 mg) on Day -14 and then relugolix 120 mg orally QD up to Day 28 and followed by apalutamide 240 mg (4 tablets of 60 mg tablets) orally QD from Day 1 up to Day 28. Upon completion of 28-day sub-study, participants were transitioned into the main study from Cycle 2 Day 1 and continued to receive apalutamide along with ADT (of investigator's choice) through Cycle 12. Each cycle was of 28 days.
Serum Testosterone Recovery (>=150 ng/dL) at Months 18 and 24 Month 18	42.0 Percentage of participants Interval 31.9 to 51.7
Serum Testosterone Recovery (>=150 ng/dL) at Months 18 and 24 Month 24	77.4 Percentage of participants Interval 66.6 to 85.1

SECONDARY outcome

Timeframe: From 1st dose of study intervention (relugolix on Day -14) up to end of sub-study (Day 28)

Population: Safety analysis set included all participants who received at least 1 dose of apalutamide. Data for this outcome measure was not planned to be collected and analyzed for main study.

An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product and it does not necessarily have a causal relationship with the intervention. TEAEs were defined as any AEs with onset or worsening on or after date of first dose of study intervention through the day of last dose in sub-study.

Outcome measures

Outcome measures
Measure	Apalutamide Plus ADT (Main Study) + Relugolix Followed by Apalutamide Plus Relugolix (Sub Study) n=12 Participants In main study, participants received apalutamide 240 milligrams (mg; 4 tablets of 60 mg) orally once daily (QD) along with ADT from Cycle 1 Day 1 up to Cycle 12. In sub-study, participants received a loading dose of relugolix 360 mg (3 tablets of 120 mg) on Day -14 and then relugolix 120 mg orally QD up to Day 28 and followed by apalutamide 240 mg (4 tablets of 60 mg tablets) orally QD from Day 1 up to Day 28. Upon completion of 28-day sub-study, participants were transitioned into the main study from Cycle 2 Day 1 and continued to receive apalutamide along with ADT (of investigator's choice) through Cycle 12. Each cycle was of 28 days.
Sub-study: Number of Participants With Treatment-emergent Adverse Events	8 Participants

Adverse Events

Main Study Plus Sub-study (Post Transition)

Serious events: 16 serious events

Other events: 107 other events

Deaths: 0 deaths

Sub Study Alone (Before Transition)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Group Medical Director Oncology

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, 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 by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application..
Publication restrictions are in place

Restriction type: OTHER

Measure	Main Study Plus Sub-study (Post Transition) n=108 participants at risk In main study, participants received apalutamide 240 milligrams (mg; 4 tablets of 60 mg) orally once daily (QD) along with ADT intramuscular or subcutaneous injection from Cycle 1 Day 1 up to Cycle 12. Each cycle was of 28 days. Sub-study participants upon completion of 28-day sub-study treatment were transitioned into the main study from Cycle 2 Day 1 and continued to receive apalutamide with ADT (oral relugolix) and were included in the main study analysis.	Sub Study Alone (Before Transition) n=12 participants at risk In sub-study, participants received a loading dose of relugolix 360 mg (3 tablets of 120 mg) on Day -14 and then relugolix 120 mg orally QD up to Day 28 and accompanied by apalutamide 240 mg (4 tablets of 60 mg tablets) orally QD from Day 1 up to Day 28. Upon completion of 28-day sub-study, participants were transitioned into the main study from Cycle 2 Day 1.
Cardiac disorders Atrial Fibrillation	1.9% 2/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).
Gastrointestinal disorders Abdominal Incarcerated Hernia	0.93% 1/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).
General disorders Chest Pain	0.93% 1/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).
Hepatobiliary disorders Cholecystitis Acute	0.93% 1/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).
Hepatobiliary disorders Hypertransaminasaemia	0.93% 1/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).
Infections and infestations Covid-19	1.9% 2/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).
Injury, poisoning and procedural complications Post Procedural Haemorrhage	0.93% 1/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Cancer	0.93% 1/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma of the Tongue	0.93% 1/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).
Nervous system disorders Syncope	1.9% 2/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).
Nervous system disorders Transient Ischaemic Attack	0.93% 1/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).
Renal and urinary disorders Bladder Neck Obstruction	0.93% 1/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).
Renal and urinary disorders Hydronephrosis	0.93% 1/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).
Skin and subcutaneous tissue disorders Stevens-Johnson Syndrome	0.93% 1/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).
Vascular disorders Hypertension	0.93% 1/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).
Vascular disorders Hypertensive Crisis	0.93% 1/108 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).	0.00% 0/12 • Main study and sub-study combined: From first dose of study drug (Cycle 1 Day 1 for main study and Cycle 2 Day 1 for sub-study [post transition into main study]) up to end of study (Month 36); sub-study alone: From Day -14 up to end of sub-study treatment (Day 28) Safety analysis set included all participants who received at least 1 dose of apalutamide. Adverse events data were planned to be collected and analyzed for unique sub-study participants alone and for combined population (along with main study after sub-study participants transitioned into main study).