Study of 177Lu-PSMA-617 In Metastatic Castrate-Resistant Prostate Cancer (VISION)

• ClinicalTrials.gov Identifier: NCT03511664
• Recruitment Status: Active, not recruiting
• First Posted: April 30, 2018
• Results First Posted: May 9, 2022
• Last Update Posted: August 11, 2022
• Sponsor: Endocyte
• Information provided by (Responsible Party): Endocyte

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer
• Interventions: Drug: 177Lu-PSMA-617; Other: Best supportive/best standard of care
• Enrollment: 831

Participant Flow

Recruitment Details	The study was conducted in 86 sites across 9 countries. Belgium (3); Canada (7); Denmark (3); France (6); Netherlands (4); Sweden (5); UK (9); US (45); Germany (4, for the sub-study only)
Pre-assignment Details

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Period Title: Overall Study
Started [1]	551	280
FAS Safety Analysis Set [2]	529	205
Progression-Free Survival (PFS) Full Analysis Set (PFS-FAS) [3]	385	196
Response Evaluable Analysis Set [4]	319	120
Completed	329	167
Not Completed	222	113
Reason Not Completed
Treatment ongoing	49	5
Entered long-term follow-up	140	50
Withdrawal by Subject	29	53
Lost to Follow-up	4	4
Physician Decision	0	1
[1] All randomized patients were included in the Full Analysis Set (FAS). Patients were included in the treatment arm to which they were randomized regardless of actual treatment received.; [2] The subset of patients in the FAS who received at least one dose of randomized treatment. Patients were included in the treatment arm corresponding to the actual treatment received.; [3] All patients randomized on or after 5-Mar-2019. Patients were included in the treatment arm to which they were randomized regardless of actual treatment received.; [4] The subset of patients in the PFS-FAS with evaluable disease by RECIST at baseline. Patients were included in the treatment arm to which they were randomized.

Baseline Characteristics

Arm/Group Title		177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone	Total
Arm/Group Description		Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator	Total of all reporting groups
Overall Number of Baseline Participants		551	280	831
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	551 participants	280 participants	831 participants
		69.7 (7.4)	70.5 (7.8)	70.0 (7.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	551 participants	280 participants	831 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	551 100.0%	280 100.0%	831 100.0%
Race/Ethnicity, Customized [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	551 participants	280 participants	831 participants
White		486	235	721
Black or African American		34	21	55
Asian		9	11	20
Other		2	0	2
Missing		20	13	33
		[1] Measure Description: Race 'Other' included Native Hawaiian or Other Pacific Islander, American Indian or Alaska Native and more than one race reported.

Outcome Measures

1. Primary Outcome

Title	Radiographic Progression-free Survival (rPFS)
Description	Radiographic progression-free survival (rPFS) was defined as the time (in months) from the date of randomization to the date of radiographic disease progression based on the central review assessment per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria or death due to any cause. Patients who were alive without radiographic progression at the analysis data cut-off were censored for rPFS at the time of their last evaluable radiographic assessment. Date of censoring for rPFS: 1) The censoring date was the date when the last evaluable radiographic assessment (CT/MRI/bone scan) determined a lack of progression; 2) If there were no evaluable assessments, censoring occurred at the date of randomization; 3) Patients who had 2 or more consecutive missed tumor assessments immediately prior to PD or death were censored at the date of the last evaluable tumor assessment prior to those missing tumor assessments.
Time Frame	From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS)

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	385	196
Median (99.2% Confidence Interval); Unit of Measure: Months
	8.7; (7.9 to 10.8)	3.4; (2.4 to 4.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC), Best Supportive/Best Standard of Care (BS/BSOC) Alone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	one-sided stratified log-rank test
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.40
	Confidence Interval	(2-Sided) 99.2%; 0.29 to 0.57
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Overall Survival (OS)
Description	Overall Survival (OS) was defined as the time (in months) from the date of randomization to the date of death due to any cause. If the patient was not known to have died, then OS was censored. The censoring date was date of the last study visit, or contact, until the cut-off date. The cut-off date was not used for last contact date, unless the patient was seen or contacted on that date.
Time Frame	From date of randomization until date of death from any cause, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	551	280
Median (95% Confidence Interval); Unit of Measure: Months
	15.3; (14.2 to 16.9)	11.3; (9.8 to 13.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC), Best Supportive/Best Standard of Care (BS/BSOC) Alone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	one-sided stratified log-rank test
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; 0.52 to 0.74
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events
Description	The distribution of adverse events (AE) was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs), through the monitoring of relevant clinical and laboratory safety parameters.
Time Frame	From randomization till 30 days safety follow-up, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

FAS Safety Analysis Set

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	529	205
Measure Type: Number; Unit of Measure: Participants
Adverse Events (AEs)	501	150
Serious Adverse Events (SAEs)	192	57

4. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	Overall Response Rate (ORR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). ORR was based on RECIST 1.1 response for patients with measurable disease at baseline per central review assessment.
Time Frame	From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

Response Evaluable Analysis Set

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	319	120
Measure Type: Count of Participants; Unit of Measure: Participants
	95 29.8%	2 1.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC), Best Supportive/Best Standard of Care (BS/BSOC) Alone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	Two-sided Wald's Chi-square test (stratified)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	24.99
	Confidence Interval	(2-Sided) 95%; 6.05 to 103.24
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	Disease control rate (DCR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) according to RECIST v1.1 per central review assessment.
Time Frame	From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

Response Evaluable Analysis Set

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	319	120
Measure Type: Count of Participants; Unit of Measure: Participants
	284 89.0%	80 66.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC), Best Supportive/Best Standard of Care (BS/BSOC) Alone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	Two-sided Wald's Chi-square test (stratified)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.79
	Confidence Interval	(2-Sided) 95%; 3.18 to 10.55
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Duration of Response (DOR)
Description	Duration of Response (DOR) was defined as the duration between the date of first documented Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) and the date of first documented radiographic progression or death due to any cause as per central review assessment.
Time Frame	From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS). Only participants for whom BOR was CR or PR and evaluable Duration of Response events (Progression or Death) included in the analysis.

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	95	2
Median (95% Confidence Interval); Unit of Measure: Months
	9.8; (9.1 to 11.7)	10.6 [1]; (NA to NA)

[1]

NA: not estimable due to insufficient number of participants with events.

7. Secondary Outcome

Title	Time to First Symptomatic Skeletal Event (SSE)
Description	Time to first Symptomatic Skeletal Event (SSE) was defined as the time (in months) from the date of randomization to the date of the SSE or death from any cause. The SSE date was the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain, or death due to any cause, whichever occurred first. SSE data for this endpoint were collected up through EOT visit. The censoring date was date of the last study visit (on or before the EOT visit).
Time Frame	From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS)

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	385	196
Median (95% Confidence Interval); Unit of Measure: Months
	11.5; (10.3 to 13.2)	6.8; (5.2 to 8.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC), Best Supportive/Best Standard of Care (BS/BSOC) Alone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Two-sided stratified log-rank test
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; 0.40 to 0.62
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Progression-free survival (PFS) was defined as the time (in months) from the date of randomization to the date of first evidence of radiographic, clinical or PSA progression or death due to any cause, whichever occurred first.
Time Frame	From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS)

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	385	196
Median (95% Confidence Interval); Unit of Measure: Months
	5.9; (5.2 to 6.6)	2.4; (2.2 to 3.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC), Best Supportive/Best Standard of Care (BS/BSOC) Alone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Two-sided stratified log-rank test
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.30
	Confidence Interval	(2-Sided) 95%; 0.24 to 0.38
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Best Percentage Change From Baseline in Prostate-specific Antigen (PSA) Level
Description	Best percentage change from baseline in PSA level was defined as the maximum percent decrease at any time post-baseline, including only patients with a baseline value and at least one non-missing post-baseline value (scheduled and unscheduled).
Time Frame	From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS). Only participants with an evaluable post-baseline and baseline samples were included in the analysis.

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	333	138
Mean (Standard Deviation); Unit of Measure: Percentage change
	-20.9 (142.6)	50.4 (118.4)

10. Secondary Outcome

Title	Percentage of Participants Achieving Prostate-specific Antigen (PSA) Response
Description	PSA response was defined as the proportion of patients who had a >= 50% decrease in PSA from baseline confirmed by a PSA measurement >= 4 weeks later.
Time Frame	From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS)

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	385	196
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	46.0; (40.9 to 51.1)	7.1; (4.0 to 11.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC), Best Supportive/Best Standard of Care (BS/BSOC) Alone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	Two-sided Wald's Chi-square test (stratified)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	11.19
	Confidence Interval	(2-Sided) 95%; 6.3 to 20.0
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Prostate-specific Antigen 80 (PSA80) Response
Description	PSA80 response was defined as the proportion of participants who had a >= 80% decrease in PSA from baseline confirmed by a PSA measurement >= 4 weeks later.
Time Frame	From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS)

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	385	196
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	33.0; (28.3 to 37.9)	2.0; (0.6 to 5.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC), Best Supportive/Best Standard of Care (BS/BSOC) Alone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	Two-sided Wald's Chi-square test (stratified)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	23.6
	Confidence Interval	(2-Sided) 95%; 8.6 to 65.1
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Duration of PSA Response
Description	Duration of PSA response was defined as the duration between the date of first document PSA response (i.e. >= 50% decrease in PSA from Baseline) and the earliest date of PSA progression, where date of PSA progression was defined as: 1) Where a decline from baseline was documented, date that a >= 25% increase in PSA and an absolute increase of 2 ng/mL or more from the nadir was documented and confirmed by a second consecutive value obtained at least 3 weeks later. Rises in PSA within the first 12 weeks of the date of first dose of randomized treatment were ignored; 2) Where no decline from baseline was documented, PSA progression was defined as a >= 25% increase from the baseline value along with an increase in absolute value of 2 ng/mL or more after 12 weeks from the date of first dose of randomized treatment (without confirmation) as specified in the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines.
Time Frame	From date of first documented PSA response till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS). Only participants with PSA progression were included in the analysis.

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	177	14
Median (95% Confidence Interval); Unit of Measure: Months
	8.9; (7.6 to 10.7)	4.4; (2.6 to 10.8)

13. Secondary Outcome

Title	Best Percentage Change From Baseline in Alkaline Phosphatase (ALP) Level
Description	Best percentage change from baseline in alkaline phosphatase (ALP) level was defined as the maximum percent decrease at any time post-baseline, including only patients with a baseline value and at least one non-missing post-baseline value (scheduled and unscheduled).
Time Frame	From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS). Only participants with an evaluable post-baseline and baseline samples were included in the analysis.

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	372	172
Mean (Standard Deviation); Unit of Measure: Percentage change
	-14.4 (46.3)	0.6 (33.8)

14. Secondary Outcome

Title	Best Percentage Change From Baseline in Lactate Dehydrogenase (LDH) Level
Description	Best percentage change from baseline in lactate dehydrogenase (LDH) level was defined as the maximum percent decrease at any time post-baseline, including only patients with a baseline value and at least one non-missing post-baseline value (scheduled and unscheduled).
Time Frame	From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS). Only participants with an evaluable post-baseline and baseline samples were included in the analysis.

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	371	168
Mean (Standard Deviation); Unit of Measure: Percentage change
	-23.1 (23.8)	-9.2 (28.2)

15. Secondary Outcome

Title	Time to Worsening in BPI-SF Pain Intensity Scale
Description	Time to worsening in BPI-SF pain intensity scale was defined as the time from randomization to the first occurring of an increase of worsening threshold (>=30% of baseline or >=2-point increase) at any time up through EOT visit compared to baseline, clinical disease progression, or death.
Time Frame	From date of randomization until date of End of Treatment (EoT), assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS-Full analysis set. Only participants with an evaluable events were included in the analysis.

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	328	166
Median (95% Confidence Interval); Unit of Measure: Months
	5.9; (4.8 to 6.9)	2.2; (1.8 to 2.8)

16. Secondary Outcome

Title	Time to Improvement After Worsening in BPI-SF Pain Intensity Scale
Description	Time to improvement after worsening in BPI-SF pain intensity scale was defined as the time from worsening of Pain Intensity score to a Pain Intensity score <= baseline.
Time Frame	From date of randomization until date of End of Treatment (EoT), assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS-Full analysis set. Only participants with an evaluable events were included in the analysis.

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	144	76
Median (95% Confidence Interval); Unit of Measure: Months
	2.8; (1.9 to 4.2)	4.2; (2.8 to 11.3)

17. Secondary Outcome

Title	Time to Worsening in BPI-SF Pain Interference Scale
Description	Time to worsening in BPI-SF pain interference scale was defined as the time from randomization to the first occurring of 1) an increase of worsening threshold (>=30% of baseline or >=2-point increase) at any time up through EOT visit compared to baseline, 2) clinical disease progression, or 3) death.
Time Frame	From date of randomization until date of End of Treatment (EoT), assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS-Full analysis set. Only participants with an evaluable events were included in the analysis.

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	330	166
Median (95% Confidence Interval); Unit of Measure: Months
	5.0; (4.2 to 6.1)	2.3; (1.7 to 2.9)

18. Secondary Outcome

Title	Time to Improvement After Worsening in BPI-SF Pain Interference Scale
Description	Time to improvement after worsening in BPI-SF pain interference scale was defined as the time from worsening of Pain Interference score to a Pain Interference score <= baseline.
Time Frame	From date of randomization until date of End of Treatment (EoT), assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS-Full analysis set. Only participants with an evaluable events were included in the analysis.

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	176	72
Median (95% Confidence Interval); Unit of Measure: Months
	3.0; (2.8 to 4.4)	2.8 [1]; (1.7 to NA)

[1]

NA: not estimable due the number of censored participants at the time the analysis cut off date was reached.

19. Secondary Outcome

Title	Time to Worsening in BPI-SF Worst Pain Intensity Scale (Time to Disease Related Pain)
Description	Time to worsening in BPI-SF worst pain intensity scale (time to disease related pain) was defined as the time from randomization to the first occurring of worsening exceeding the threshold threshold (>=30% of baseline or >=2 point increase) at any time up through EOT visit compared to baseline, clinical disease progression, or death.
Time Frame	From date of randomization until date of End of Treatment (EoT), assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS-Full analysis set. Only participants with an evaluable events were included in the analysis.

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	332	169
Median (95% Confidence Interval); Unit of Measure: Months
	5.0; (4.2 to 5.9)	2.0; (1.7 to 2.2)

20. Secondary Outcome

Title	Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale
Description	The BPI-SF is a generic pain assessment tool used in research and practice for pain assessment in musculoskeletal conditions. The higher the BPI-SF score, the worse the pain. The BPI-SF consists of 4 questions regarding pain intensity (worst pain intensity, least pain intensity, average pain intensity and pain right now), 2 questions on the use of analgesics, and 7 questions on how the level pain has interfered with the subject's life (General Activity, Mood, Walking Ability, Normal Work, Relations with other people, Sleep, Enjoyment of Life). Intensity items consist of an 11-response rating scale scored from 0 ("No Pain") to 10 ("Pain As Bad As You Can Imagine"). BPI-SF Pain intensity is the mean of non-missing items of the 4 individual scales, if there are 3 or more items not missing; otherwise this scale is set to missing.
Time Frame	Baseline (BL), Cycle 2 to Cycle 13 (Week 1 Day 1), End of Treatment (EoT) (cycle duration for Cycle 1-6 = 6 weeks and for Cycle 7 and beyond = 12 weeks)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS). Only participants with non-missing score both at Baseline and at post-baseline visits were included in the analysis.

Arm/Group Title		177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:		Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed		385	196
Mean (Standard Deviation); Unit of Measure: Score on a scale
Cycle 2, Week 1, Day 1 change from BL	Number Analyzed	311 participants	100 participants
		-0.59 (2.037)	0.21 (2.404)
Cycle 3, Week 1, Day 1 change from BL	Number Analyzed	274 participants	52 participants
		-0.62 (1.924)	0.02 (2.033)
Cycle 4, Week 1, Day 1 change from BL	Number Analyzed	223 participants	32 participants
		-0.42 (2.017)	0.26 (2.383)
Cycle 5, Week 1, Day 1 change from BL	Number Analyzed	183 participants	21 participants
		-0.49 (1.957)	0.55 (3.144)
Cycle 6, Week 1, Day 1 change from BL	Number Analyzed	162 participants	13 participants
		-0.41 (1.897)	0.10 (2.740)
Cycle 7, Week 1, Day 1 change from BL	Number Analyzed	123 participants	11 participants
		-0.48 (2.011)	-0.32 (1.585)
Cycle 8, Week 1, Day 1 change from BL	Number Analyzed	86 participants	5 participants
		-0.18 (1.759)	-1.10 (2.205)
Cycle 9, Week 1, Day 1 change from BL	Number Analyzed	55 participants	6 participants
		-0.70 (2.157)	0.13 (1.780)
Cycle 10, Week 1, Day 1 change from BL	Number Analyzed	33 participants	2 participants
		0.02 (1.513)	0.50 (1.768)
Cycle 11, Week 1, Day 1 change from BL	Number Analyzed	12 participants	2 participants
		-0.40 (0.956)	0.75 (1.768)
Cycle 12, Week 1, Day 1 change from BL	Number Analyzed	4 participants	0 participants
		-1.00 (0.354)
Cycle 13, Week 1, Day 1 change from BL	Number Analyzed	1 participants	0 participants
		-0.75 [1] (NA)
End of Treatment (EoT) change from BL	Number Analyzed	165 participants	88 participants
		0.46 (2.415)	0.50 (2.405)

[1]

NA: Only one participant analyzed

21. Secondary Outcome

Title	Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale
Description	"The BPI-SF is a generic pain assessment tool used in research and practice for pain assessment in musculoskeletal conditions. The higher the BPI-SF score, the worse the pain. The BPI-SF consists of 4 questions regarding pain intensity (worst pain intensity, least pain intensity, average pain intensity and pain right now), 2 questions on the use of analgesics, and 7 questions on how the level pain has interfered with the subject's life (General Activity, Mood, Walking Ability, Normal Work, Relations with other people, Sleep, Enjoyment of Life). Interference items consist of scores from 0 ("Does Not Interfere") to 10 ("Completely Interferes"). BPI-SF Interference scale is the mean of non-missing items of the 7 items on pain interference, if there are 4 or more items not missing; otherwise this scale is set to missing."
Time Frame	Baseline (BL), Cycle 2 to Cycle 13 (Week 1 Day 1), End of Treatment (EoT) (cycle duration for Cycle 1-6 = 6 weeks and for Cycle 7 and beyond = 12 weeks)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS). Only participants with non-missing score both at Baseline and at post-baseline visits were included in the analysis.

Arm/Group Title		177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:		Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed		385	196
Mean (Standard Deviation); Unit of Measure: Score on a scale
Cycle 2, Week 1, Day 1 change from BL	Number Analyzed	311 participants	100 participants
		-0.40 (2.167)	0.58 (2.700)
Cycle 3, Week 1, Day 1 change from BL	Number Analyzed	274 participants	52 participants
		-0.35 (2.348)	-0.15 (2.216)
Cycle 4, Week 1, Day 1 change from BL	Number Analyzed	223 participants	32 participants
		-0.33 (2.249)	0.21 (2.762)
Cycle 5, Week 1, Day 1 change from BL	Number Analyzed	183 participants	21 participants
		-0.32 (2.223)	0.52 (3.480)
Cycle 6, Week 1, Day 1 change from BL	Number Analyzed	161 participants	13 participants
		-0.28 (2.166)	0.49 (3.354)
Cycle 7, Week 1, Day 1 change from BL	Number Analyzed	122 participants	11 participants
		-0.22 (1.882)	0.06 (2.570)
Cycle 8, Week 1, Day 1 change from BL	Number Analyzed	86 participants	5 participants
		0.18 (1.926)	-0.26 (1.291)
Cycle 9, Week 1, Day 1 change from BL	Number Analyzed	55 participants	6 participants
		-0.15 (1.751)	0.12 (1.667)
Cycle 10, Week 1, Day 1 change from BL	Number Analyzed	33 participants	2 participants
		0.62 (2.141)	1.50 (1.313)
Cycle 11, Week 1, Day 1 change from BL	Number Analyzed	12 participants	2 participants
		-0.06 (1.334)	0.36 (4.748)
Cycle 12, Week 1, Day 1 change from BL	Number Analyzed	4 participants	0 participants
		-0.89 (0.914)
Cycle 13, Week 1, Day 1 change from BL	Number Analyzed	1 participants	0 participants
		-0.43 [1] (NA)
End of Treatment (EoT) change from BL	Number Analyzed	165 participants	88 participants
		0.73 (2.756)	0.29 (2.385)

[1]

NA: Only one participant analyzed

22. Secondary Outcome

Title	Time to Worsening in FACT-P Total Score
Description	Time to worsening was defined as the time from randomization to the first occurring of a >=10 point decrease in FACT-P total score compared to baseline, clinical disease progression, or death.
Time Frame	From date of randomization until date of End of Treatment (EoT), assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS-Full analysis set

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	385	196
Median (95% Confidence Interval); Unit of Measure: Months
	5.7; (4.8 to 6.6)	2.2; (1.8 to 2.8)

23. Secondary Outcome

Title	Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score
Description	The FACT-P total score (range 0-156) consist of five subscales (Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24)) and a functional well-being and prostate cancer subscale (range 0-48). Higher scores indicate higher degree of functioning and better quality of life.
Time Frame	Baseline (BL), Cycle 2 to Cycle 13 (Week 1 Day 1), End of Treatment (EoT) (cycle duration for Cycle 1-6 = 6 weeks and for Cycle 7 and beyond = 12 weeks)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS). Only participants with non-missing score both at Baseline and at post-baseline visits were included in the analysis.

Arm/Group Title		177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:		Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed		385	196
Mean (Standard Deviation); Unit of Measure: Score on a scale
Cycle 2, Week 1, Day 1 change from BL	Number Analyzed	304 participants	100 participants
		3.6 (16.63)	-7.2 (17.85)
Cycle 3, Week 1, Day 1 change from BL	Number Analyzed	269 participants	52 participants
		3.8 (17.48)	-2.6 (14.00)
Cycle 4, Week 1, Day 1 change from BL	Number Analyzed	222 participants	32 participants
		5.4 (15.93)	-1.3 (18.40)
Cycle 5, Week 1, Day 1 change from BL	Number Analyzed	181 participants	21 participants
		4.0 (16.24)	-5.9 (27.83)
Cycle 6, Week 1, Day 1 change from BL	Number Analyzed	158 participants	13 participants
		4.1 (15.22)	-5.0 (26.87)
Cycle 7, Week 1, Day 1 change from BL	Number Analyzed	122 participants	11 participants
		4.9 (16.47)	-2.9 (17.89)
Cycle 8, Week 1, Day 1 change from BL	Number Analyzed	86 participants	5 participants
		3.8 (15.87)	-13.0 (32.76)
Cycle 9, Week 1, Day 1 change from BL	Number Analyzed	54 participants	6 participants
		3.8 (14.22)	6.9 (5.92)
Cycle 10, Week 1, Day 1 change from BL	Number Analyzed	33 participants	2 participants
		0.0 (18.27)	0.2 (14.14)
Cycle 11, Week 1, Day 1 change from BL	Number Analyzed	12 participants	2 participants
		-0.8 (20.99)	8.2 (33.71)
Cycle 12, Week 1, Day 1 change from BL	Number Analyzed	4 participants	0 participants
		10.3 (12.11)
Cycle 13, Week 1, Day 1 change from BL	Number Analyzed	1 participants	0 participants
		30.0 [1] (NA)
End of Treatment (EoT) change from BL	Number Analyzed	161 participants	86 participants
		-9.4 (21.64)	-10.4 (18.59)

[1]

NA: Only one participant analyzed

24. Secondary Outcome

Title	Time to Worsening in EQ-5D-5L Utility Score
Description	Time to worsening for utility score was defined as time from randomization to the first occurrence of worsening in utility score relative to baseline (no change or any decrease), clinical disease progression, or death.
Time Frame	From date of randomization until date of End of Treatment (EoT), assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS-Full analysis set

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	385	196
Median (95% Confidence Interval); Unit of Measure: Months
	1.0; (0.7 to 1.8)	0.5; (0.4 to 1.0)

25. Secondary Outcome

Title	Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score
Description	The EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3=moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions. A utility score was obtained by using a weighted combination of the levels of the five dimension-scales. The weights were based on value sets which were country-specific for the U.K. Utility scores ranges from the lowest possible score for a living patient of -0.594 (when all responses are '5') to 1 (when all responses are '1').If a patient died, he was assigned a score of 0 on the date of death.
Time Frame	Baseline (BL), Cycle 2 to Cycle 13 (Week 1 Day 1), End of Treatment (EoT) (cycle duration for Cycle 1-6 = 6 weeks and for Cycle 7 and beyond = 12 weeks)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS). Only participants with non-missing score both at Baseline and at post-baseline visits were included in the analysis.

Arm/Group Title		177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:		Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed		385	196
Mean (Standard Deviation); Unit of Measure: Score on a scale
Cycle 2, Week 1, Day 1 change from BL	Number Analyzed	304 participants	100 participants
		0.0221 (0.17693)	-0.0897 (0.24973)
Cycle 3, Week 1, Day 1 change from BL	Number Analyzed	273 participants	53 participants
		0.0297 (0.18817)	-0.0331 (0.14155)
Cycle 4, Week 1, Day 1 change from BL	Number Analyzed	221 participants	32 participants
		0.0292 (0.17713)	-0.0818 (0.23752)
Cycle 5, Week 1, Day 1 change from BL	Number Analyzed	180 participants	21 participants
		0.0398 (0.16827)	-0.0673 (0.28633)
Cycle 6, Week 1, Day 1 change from BL	Number Analyzed	159 participants	13 participants
		0.0342 (0.17950)	-0.0110 (0.17842)
Cycle 7, Week 1, Day 1 change from BL	Number Analyzed	121 participants	11 participants
		0.0252 (0.16127)	-0.0088 (0.09081)
Cycle 8, Week 1, Day 1 change from BL	Number Analyzed	84 participants	5 participants
		0.0285 (0.18017)	-0.0296 (0.14964)
Cycle 9, Week 1, Day 1 change from BL	Number Analyzed	54 participants	6 participants
		0.0100 (0.17447)	0.0087 (0.08167)
Cycle 10, Week 1, Day 1 change from BL	Number Analyzed	33 participants	2 participants
		0.0134 (0.15764)	-0.0655 (0.09263)
Cycle 11, Week 1, Day 1 change from BL	Number Analyzed	12 participants	2 participants
		0.0464 (0.16858)	0.0250 (0.19940)
Cycle 12, Week 1, Day 1 change from BL	Number Analyzed	4 participants	0 participants
		0.1118 (0.13833)
Cycle 13, Week 1, Day 1 change from BL	Number Analyzed	1 participants	0 participants
		0.0640 [1] (NA)
End of Treatment (EoT) change from BL	Number Analyzed	163 participants	85 participants
		-0.0939 (0.22698)	-0.0900 (0.21223)

[1]

NA: Only one participant analyzed

26. Secondary Outcome

Title	Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS
Description	The EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ VAS records the patient's self-rated health on a vertical visual analogue 0-100 scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The higher the EQ-VAS score, the better the QoL.
Time Frame	Baseline (BL), Cycle 2 to Cycle 13 (Week 1 Day 1), End of Treatment (EoT) (cycle duration for Cycle 1-6 = 6 weeks and for Cycle 7 and beyond = 12 weeks)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS). Only participants with non-missing score both at Baseline and at post-baseline visits were included in the analysis.

Arm/Group Title		177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:		Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed		385	196
Mean (Standard Deviation); Unit of Measure: Score on a scale
Cycle 2, Week 1, Day 1 change from BL	Number Analyzed	305 participants	100 participants
		1.8 (19.98)	-7.2 (20.31)
Cycle 3, Week 1, Day 1 change from BL	Number Analyzed	272 participants	53 participants
		1.4 (19.82)	-3.8 (21.50)
Cycle 4, Week 1, Day 1 change from BL	Number Analyzed	221 participants	32 participants
		2.8 (19.18)	-1.7 (18.73)
Cycle 5, Week 1, Day 1 change from BL	Number Analyzed	180 participants	21 participants
		4.0 (17.30)	-8.5 (28.88)
Cycle 6, Week 1, Day 1 change from BL	Number Analyzed	159 participants	13 participants
		2.1 (19.61)	3.2 (19.43)
Cycle 7, Week 1, Day 1 change from BL	Number Analyzed	121 participants	11 participants
		3.6 (20.64)	5.9 (12.79)
Cycle 8, Week 1, Day 1 change from BL	Number Analyzed	84 participants	5 participants
		0.6 (17.18)	13.8 (16.60)
Cycle 9, Week 1, Day 1 change from BL	Number Analyzed	54 participants	6 participants
		0.1 (19.68)	6.3 (20.82)
Cycle 10, Week 1, Day 1 change from BL	Number Analyzed	33 participants	2 participants
		2.9 (13.97)	-8.0 (2.83)
Cycle 11, Week 1, Day 1 change from BL	Number Analyzed	12 participants	2 participants
		5.8 (10.33)	-9.0 (28.28)
Cycle 12, Week 1, Day 1 change from BL	Number Analyzed	4 participants	0 participants
		4.5 (13.03)
Cycle 13, Week 1, Day 1 change from BL	Number Analyzed	1 participants	0 participants
		-5.0 [1] (NA)
End of Treatment (EoT) change from BL	Number Analyzed	163 participants	86 participants
		-8.9 (22.07)	-10.1 (21.49)

[1]

NA: Only one participant analyzed

27. Secondary Outcome

Title	Number of Participants Hospitalized as In-patient
Description	The number of hospitalizations (yes/no) (admitted as in-patient) was collected as part of the hospital admission for health economic evaluations.
Time Frame	From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS)

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	385	196
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	157 40.8%	59 30.1%
No	228 59.2%	137 69.9%

28. Secondary Outcome

Title	Duration of Time in Hospital Following 177Lu-PSMA-617 Administration
Description	The duration of time in hospital following 177Lu-PSMA-617 administration (hours) was the time span of patient discharged as captured on the 177Lu-PSMA-617 administration Case Report Form (CRF).
Time Frame	From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS)

Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed	341	0
Mean (Standard Deviation); Unit of Measure: Hours
	28.25 (46.578)

29. Secondary Outcome

Title	Concomitant Drug Use for Health Economics Analysis
Description	The list of concomitant drugs as captured on the concomitant medication/therapy CRF page to include in each category was pre-specified and flagged prior to the pre planned analyses. (1) Bisphosphonates (including but not limited to zoledronic acid, alendronic acid, etc.), denosumab, and other bone targeted therapies), (2) Corticosteroids for systemic use (3), Antifungals for systemic use (i.e. ketoconazole), (4) ESA (erythropoietin stimulating agents, i.e. epoetin alfa), (5) Granulocyte macrophage colony-stimulating factor (GM-CSF), (6) Novel androgen axis drugs (NAADs; i.e. enzalutamide, abiraterone, apalutamide), (7) Antiemetics and (8) Opioid analgesics use for cancer-related pain.
Time Frame	From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS)

Arm/Group Title		177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:		Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed		385	196
Measure Type: Count of Participants; Unit of Measure: Participants
Bisphosphonates	Yes	169 43.9%	88 44.9%
	No	216 56.1%	108 55.1%
Corticosteroids	Yes	246 63.9%	113 57.7%
	No	139 36.1%	83 42.3%
Antifungals	Yes	1 0.3%	4 2.0%
	No	384 99.7%	192 98.0%
Erythropoietin Stimulating Agents	Yes	8 2.1%	2 1.0%
	No	377 97.9%	194 99.0%
Granulocyte macrophage colony-stimulating factor	Yes	7 1.8%	3 1.5%
	No	378 98.2%	193 98.5%
Novel Androgen Axis Drugs	Yes	188 48.8%	115 58.7%
	No	197 51.2%	81 41.3%
Antiemetics	Yes	232 60.3%	45 23.0%
	No	153 39.7%	151 77.0%
Opioid analgesics	Yes	199 51.7%	96 49.0%
	No	186 48.3%	100 51.0%

30. Secondary Outcome

Title	Therapeutic Interventions for Health Economics Analysis
Description	The list of therapeutic interventions was pre-specified and flagged prior to the pre planned analyses as captured on: 1) the concurrent radiotherapy CRF page to include local external beam radiotherapy (inclusive of palliative external radiation), 2) on the concomitant medication/therapy CRF page to include blood transfusion (full blood or derivates).
Time Frame	From date of randomization till 30 days safety fup, assessed up to 43 months (Final OS analysis cut-off date = 27-Jan-2021)

Outcome Measure Data

Analysis Population Description

PFS Full Analysis Set (PFS-FAS)

Arm/Group Title		177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description:		Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
Overall Number of Participants Analyzed		385	196
Measure Type: Count of Participants; Unit of Measure: Participants
Local external beam therapy	Yes	63 16.4%	37 18.9%
	No	322 83.6%	159 81.1%
Blood transfusion	Yes	74 19.2%	13 6.6%
	No	311 80.8%	183 93.4%

Adverse Events

Time Frame	From first dose of study treatment up to 30 days after last dose (maximum 27 months).
Adverse Event Reporting Description	Adverse Events (AEs) and All-cause mortality were collected in the FAS Safety Analysis Set
Arm/Group Title	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
Arm/Group Description	Patients randomized to receive the investigational product received 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) might be used	Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator
All-Cause Mortality
	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	66/529 (12.48%)	19/205 (9.27%)
Serious Adverse Events
	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	192/529 (36.29%)	57/205 (27.80%)
Blood and lymphatic system disorders
Anaemia † 1	15/529 (2.84%)	1/205 (0.49%)
Bone marrow failure † 1	1/529 (0.19%)	0/205 (0.00%)
Febrile neutropenia † 1	2/529 (0.38%)	0/205 (0.00%)
Leukopenia † 1	2/529 (0.38%)	0/205 (0.00%)
Neutropenia † 1	1/529 (0.19%)	0/205 (0.00%)
Pancytopenia † 1	6/529 (1.13%)	0/205 (0.00%)
Thrombocytopenia † 1	3/529 (0.57%)	0/205 (0.00%)
Cardiac disorders
Arrhythmia † 1	1/529 (0.19%)	0/205 (0.00%)
Atrial fibrillation † 1	1/529 (0.19%)	0/205 (0.00%)
Cardiac failure † 1	1/529 (0.19%)	0/205 (0.00%)
Cardiac failure congestive † 1	2/529 (0.38%)	0/205 (0.00%)
Cardio-respiratory arrest † 1	0/529 (0.00%)	1/205 (0.49%)
Cardiomyopathy † 1	1/529 (0.19%)	0/205 (0.00%)
Myocardial infarction † 1	1/529 (0.19%)	0/205 (0.00%)
Supraventricular tachycardia † 1	0/529 (0.00%)	1/205 (0.49%)
Ventricular tachycardia † 1	2/529 (0.38%)	0/205 (0.00%)
Congenital, familial and genetic disorders
Vascular malformation † 1	1/529 (0.19%)	0/205 (0.00%)
Ear and labyrinth disorders
Vertigo † 1	1/529 (0.19%)	0/205 (0.00%)
Endocrine disorders
Adrenal insufficiency † 1	1/529 (0.19%)	0/205 (0.00%)
Inappropriate antidiuretic hormone secretion † 1	0/529 (0.00%)	1/205 (0.49%)
Eye disorders
Vision blurred † 1	1/529 (0.19%)	0/205 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	4/529 (0.76%)	1/205 (0.49%)
Ascites † 1	1/529 (0.19%)	0/205 (0.00%)
Constipation † 1	5/529 (0.95%)	1/205 (0.49%)
Diarrhoea † 1	0/529 (0.00%)	1/205 (0.49%)
Duodenal ulcer † 1	1/529 (0.19%)	0/205 (0.00%)
Dysphagia † 1	1/529 (0.19%)	1/205 (0.49%)
Gastric haemorrhage † 1	1/529 (0.19%)	0/205 (0.00%)
Gastrointestinal haemorrhage † 1	0/529 (0.00%)	1/205 (0.49%)
Gastrooesophageal reflux disease † 1	1/529 (0.19%)	0/205 (0.00%)
Haematemesis † 1	1/529 (0.19%)	0/205 (0.00%)
Intestinal perforation † 1	1/529 (0.19%)	0/205 (0.00%)
Intestinal pseudo-obstruction † 1	1/529 (0.19%)	0/205 (0.00%)
Large intestinal obstruction † 1	1/529 (0.19%)	0/205 (0.00%)
Lower gastrointestinal haemorrhage † 1	1/529 (0.19%)	1/205 (0.49%)
Nausea † 1	3/529 (0.57%)	1/205 (0.49%)
Rectal haemorrhage † 1	1/529 (0.19%)	0/205 (0.00%)
Small intestinal obstruction † 1	1/529 (0.19%)	1/205 (0.49%)
Stomatitis † 1	1/529 (0.19%)	0/205 (0.00%)
Upper gastrointestinal haemorrhage † 1	1/529 (0.19%)	0/205 (0.00%)
Volvulus † 1	0/529 (0.00%)	1/205 (0.49%)
Vomiting † 1	5/529 (0.95%)	1/205 (0.49%)
General disorders
Asthenia † 1	0/529 (0.00%)	1/205 (0.49%)
Disease progression † 1	2/529 (0.38%)	1/205 (0.49%)
Euthanasia † 1	1/529 (0.19%)	0/205 (0.00%)
Fatigue † 1	2/529 (0.38%)	0/205 (0.00%)
General physical health deterioration † 1	0/529 (0.00%)	1/205 (0.49%)
Generalised oedema † 1	1/529 (0.19%)	0/205 (0.00%)
Influenza like illness † 1	0/529 (0.00%)	1/205 (0.49%)
Malaise † 1	1/529 (0.19%)	0/205 (0.00%)
Multiple organ dysfunction syndrome † 1	1/529 (0.19%)	0/205 (0.00%)
Oedema † 1	0/529 (0.00%)	1/205 (0.49%)
Oedema peripheral † 1	1/529 (0.19%)	0/205 (0.00%)
Pain † 1	5/529 (0.95%)	1/205 (0.49%)
Pyrexia † 1	7/529 (1.32%)	0/205 (0.00%)
Systemic inflammatory response syndrome † 1	1/529 (0.19%)	0/205 (0.00%)
Hepatobiliary disorders
Acute hepatic failure † 1	1/529 (0.19%)	0/205 (0.00%)
Bile duct stenosis † 1	1/529 (0.19%)	0/205 (0.00%)
Cholecystitis † 1	1/529 (0.19%)	0/205 (0.00%)
Cholestasis † 1	1/529 (0.19%)	0/205 (0.00%)
Hepatic failure † 1	1/529 (0.19%)	0/205 (0.00%)
Hepatic lesion † 1	1/529 (0.19%)	0/205 (0.00%)
Hepatocellular injury † 1	0/529 (0.00%)	2/205 (0.98%)
Infections and infestations
Appendicitis † 1	2/529 (0.38%)	0/205 (0.00%)
Bacterial sepsis † 1	1/529 (0.19%)	0/205 (0.00%)
Bronchitis † 1	1/529 (0.19%)	0/205 (0.00%)
COVID-19 † 1	1/529 (0.19%)	0/205 (0.00%)
Diverticulitis † 1	1/529 (0.19%)	0/205 (0.00%)
Enterococcal bacteraemia † 1	1/529 (0.19%)	0/205 (0.00%)
Enterocolitis infectious † 1	1/529 (0.19%)	0/205 (0.00%)
Escherichia sepsis † 1	1/529 (0.19%)	0/205 (0.00%)
Extradural abscess † 1	1/529 (0.19%)	0/205 (0.00%)
Fungaemia † 1	1/529 (0.19%)	0/205 (0.00%)
Herpes zoster † 1	1/529 (0.19%)	0/205 (0.00%)
Infection † 1	3/529 (0.57%)	2/205 (0.98%)
Kidney infection † 1	1/529 (0.19%)	0/205 (0.00%)
Klebsiella sepsis † 1	1/529 (0.19%)	0/205 (0.00%)
Lower respiratory tract infection † 1	1/529 (0.19%)	0/205 (0.00%)
Osteomyelitis † 1	1/529 (0.19%)	0/205 (0.00%)
Pharyngitis † 1	0/529 (0.00%)	1/205 (0.49%)
Pneumonia † 1	7/529 (1.32%)	3/205 (1.46%)
Pyelonephritis † 1	1/529 (0.19%)	0/205 (0.00%)
Pyelonephritis acute † 1	1/529 (0.19%)	0/205 (0.00%)
Sepsis † 1	10/529 (1.89%)	2/205 (0.98%)
Septic shock † 1	2/529 (0.38%)	0/205 (0.00%)
Staphylococcal bacteraemia † 1	1/529 (0.19%)	0/205 (0.00%)
Urinary tract infection † 1	13/529 (2.46%)	1/205 (0.49%)
Urosepsis † 1	3/529 (0.57%)	0/205 (0.00%)
Viral infection † 1	1/529 (0.19%)	0/205 (0.00%)
Wound infection † 1	1/529 (0.19%)	0/205 (0.00%)
Injury, poisoning and procedural complications
Acetabulum fracture † 1	1/529 (0.19%)	0/205 (0.00%)
Fall † 1	1/529 (0.19%)	1/205 (0.49%)
Femoral neck fracture † 1	1/529 (0.19%)	0/205 (0.00%)
Femur fracture † 1	1/529 (0.19%)	0/205 (0.00%)
Hip fracture † 1	1/529 (0.19%)	0/205 (0.00%)
Muscle strain † 1	0/529 (0.00%)	1/205 (0.49%)
Overdose † 1	1/529 (0.19%)	0/205 (0.00%)
Rib fracture † 1	0/529 (0.00%)	1/205 (0.49%)
Spinal fracture † 1	2/529 (0.38%)	0/205 (0.00%)
Subdural haematoma † 1	4/529 (0.76%)	2/205 (0.98%)
Wound complication † 1	0/529 (0.00%)	1/205 (0.49%)
Investigations
Blood creatinine increased † 1	0/529 (0.00%)	1/205 (0.49%)
Metabolism and nutrition disorders
Cachexia † 1	1/529 (0.19%)	0/205 (0.00%)
Decreased appetite † 1	1/529 (0.19%)	0/205 (0.00%)
Dehydration † 1	5/529 (0.95%)	1/205 (0.49%)
Failure to thrive † 1	2/529 (0.38%)	0/205 (0.00%)
Hypervolaemia † 1	0/529 (0.00%)	1/205 (0.49%)
Hypocalcaemia † 1	1/529 (0.19%)	0/205 (0.00%)
Hypoglycaemia † 1	1/529 (0.19%)	1/205 (0.49%)
Hypokalaemia † 1	2/529 (0.38%)	1/205 (0.49%)
Hyponatraemia † 1	0/529 (0.00%)	1/205 (0.49%)
Hypophosphataemia † 1	0/529 (0.00%)	1/205 (0.49%)
Tumour lysis syndrome † 1	1/529 (0.19%)	0/205 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	2/529 (0.38%)	0/205 (0.00%)
Back pain † 1	9/529 (1.70%)	3/205 (1.46%)
Bone pain † 1	6/529 (1.13%)	2/205 (0.98%)
Flank pain † 1	1/529 (0.19%)	0/205 (0.00%)
Intervertebral disc compression † 1	1/529 (0.19%)	0/205 (0.00%)
Intervertebral disc protrusion † 1	1/529 (0.19%)	0/205 (0.00%)
Neck pain † 1	2/529 (0.38%)	0/205 (0.00%)
Osteolysis † 1	1/529 (0.19%)	0/205 (0.00%)
Pain in extremity † 1	1/529 (0.19%)	0/205 (0.00%)
Pathological fracture † 1	1/529 (0.19%)	0/205 (0.00%)
Spinal pain † 1	1/529 (0.19%)	0/205 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system † 1	2/529 (0.38%)	0/205 (0.00%)
Metastases to meninges † 1	1/529 (0.19%)	0/205 (0.00%)
Nervous system disorders
Brain oedema † 1	0/529 (0.00%)	1/205 (0.49%)
Cauda equina syndrome † 1	1/529 (0.19%)	1/205 (0.49%)
Cerebellar infarction † 1	1/529 (0.19%)	0/205 (0.00%)
Cerebral haemorrhage † 1	1/529 (0.19%)	0/205 (0.00%)
Cerebral infarction † 1	1/529 (0.19%)	0/205 (0.00%)
Cognitive disorder † 1	1/529 (0.19%)	0/205 (0.00%)
Diplegia † 1	0/529 (0.00%)	1/205 (0.49%)
Dizziness † 1	2/529 (0.38%)	0/205 (0.00%)
Dysarthria † 1	1/529 (0.19%)	0/205 (0.00%)
Encephalopathy † 1	0/529 (0.00%)	1/205 (0.49%)
Haemorrhage intracranial † 1	2/529 (0.38%)	0/205 (0.00%)
Headache † 1	2/529 (0.38%)	0/205 (0.00%)
Hypoglossal nerve paralysis † 1	1/529 (0.19%)	0/205 (0.00%)
Ischaemic stroke † 1	3/529 (0.57%)	0/205 (0.00%)
Loss of consciousness † 1	1/529 (0.19%)	0/205 (0.00%)
Metabolic encephalopathy † 1	1/529 (0.19%)	1/205 (0.49%)
Myelopathy † 1	0/529 (0.00%)	1/205 (0.49%)
Pachymeningitis † 1	1/529 (0.19%)	0/205 (0.00%)
Paraesthesia † 1	2/529 (0.38%)	0/205 (0.00%)
Peripheral motor neuropathy † 1	1/529 (0.19%)	0/205 (0.00%)
Radiculopathy † 1	2/529 (0.38%)	0/205 (0.00%)
Seizure † 1	1/529 (0.19%)	0/205 (0.00%)
Spinal cord compression † 1	6/529 (1.13%)	10/205 (4.88%)
Spinal cord disorder † 1	0/529 (0.00%)	1/205 (0.49%)
Syncope † 1	4/529 (0.76%)	0/205 (0.00%)
Transient ischaemic attack † 1	1/529 (0.19%)	0/205 (0.00%)
Tremor † 1	1/529 (0.19%)	0/205 (0.00%)
Psychiatric disorders
Confusional state † 1	2/529 (0.38%)	1/205 (0.49%)
Delirium † 1	1/529 (0.19%)	1/205 (0.49%)
Mental status changes † 1	3/529 (0.57%)	0/205 (0.00%)
Mixed anxiety and depressive disorder † 1	1/529 (0.19%)	0/205 (0.00%)
Renal and urinary disorders
Acute kidney injury † 1	9/529 (1.70%)	6/205 (2.93%)
Dysuria † 1	1/529 (0.19%)	0/205 (0.00%)
Haematuria † 1	11/529 (2.08%)	1/205 (0.49%)
Hydronephrosis † 1	1/529 (0.19%)	1/205 (0.49%)
Malignant urinary tract obstruction † 1	1/529 (0.19%)	0/205 (0.00%)
Nephrolithiasis † 1	1/529 (0.19%)	0/205 (0.00%)
Renal tubular acidosis † 1	1/529 (0.19%)	0/205 (0.00%)
Urinary retention † 1	5/529 (0.95%)	2/205 (0.98%)
Urinary tract obstruction † 1	4/529 (0.76%)	0/205 (0.00%)
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	1/529 (0.19%)	0/205 (0.00%)
Penile pain † 1	1/529 (0.19%)	0/205 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	1/529 (0.19%)	0/205 (0.00%)
Chronic obstructive pulmonary disease † 1	1/529 (0.19%)	0/205 (0.00%)
Dyspnoea † 1	5/529 (0.95%)	1/205 (0.49%)
Epistaxis † 1	1/529 (0.19%)	0/205 (0.00%)
Haemoptysis † 1	1/529 (0.19%)	0/205 (0.00%)
Hypoxia † 1	1/529 (0.19%)	0/205 (0.00%)
Pleural effusion † 1	2/529 (0.38%)	1/205 (0.49%)
Pneumonia aspiration † 1	1/529 (0.19%)	0/205 (0.00%)
Pulmonary embolism † 1	6/529 (1.13%)	2/205 (0.98%)
Pulmonary hypertension † 1	0/529 (0.00%)	1/205 (0.49%)
Surgical and medical procedures
Neck dissection † 1	1/529 (0.19%)	0/205 (0.00%)
Pain management † 1	1/529 (0.19%)	0/205 (0.00%)
Vascular disorders
Aortic stenosis † 1	1/529 (0.19%)	0/205 (0.00%)
Arteriosclerosis † 1	0/529 (0.00%)	1/205 (0.49%)
Deep vein thrombosis † 1	3/529 (0.57%)	0/205 (0.00%)
Embolism † 1	2/529 (0.38%)	0/205 (0.00%)
Hypotension † 1	4/529 (0.76%)	0/205 (0.00%)
Orthostatic hypotension † 1	1/529 (0.19%)	0/205 (0.00%)
1 Term from vocabulary, MedDRA (23.1); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)	Best Supportive/Best Standard of Care (BS/BSOC) Alone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	501/529 (94.71%)	150/205 (73.17%)
Blood and lymphatic system disorders
Anaemia † 1	160/529 (30.25%)	26/205 (12.68%)
Leukopenia † 1	66/529 (12.48%)	4/205 (1.95%)
Lymphopenia † 1	75/529 (14.18%)	8/205 (3.90%)
Neutropenia † 1	45/529 (8.51%)	3/205 (1.46%)
Thrombocytopenia † 1	91/529 (17.20%)	9/205 (4.39%)
Gastrointestinal disorders
Abdominal pain † 1	29/529 (5.48%)	6/205 (2.93%)
Constipation † 1	103/529 (19.47%)	23/205 (11.22%)
Diarrhoea † 1	100/529 (18.90%)	5/205 (2.44%)
Dry mouth † 1	205/529 (38.75%)	1/205 (0.49%)
Nausea † 1	185/529 (34.97%)	33/205 (16.10%)
Vomiting † 1	97/529 (18.34%)	12/205 (5.85%)
General disorders
Asthenia † 1	34/529 (6.43%)	16/205 (7.80%)
Fatigue † 1	227/529 (42.91%)	47/205 (22.93%)
Oedema peripheral † 1	50/529 (9.45%)	13/205 (6.34%)
Pain † 1	28/529 (5.29%)	9/205 (4.39%)
Pyrexia † 1	30/529 (5.67%)	7/205 (3.41%)
Infections and infestations
Urinary tract infection † 1	52/529 (9.83%)	1/205 (0.49%)
Injury, poisoning and procedural complications
Fall † 1	37/529 (6.99%)	12/205 (5.85%)
Investigations
Blood creatinine increased † 1	28/529 (5.29%)	4/205 (1.95%)
Weight decreased † 1	57/529 (10.78%)	18/205 (8.78%)
Metabolism and nutrition disorders
Decreased appetite † 1	111/529 (20.98%)	30/205 (14.63%)
Hypocalcaemia † 1	36/529 (6.81%)	7/205 (3.41%)
Hypokalaemia † 1	39/529 (7.37%)	7/205 (3.41%)
Hypophosphataemia † 1	28/529 (5.29%)	7/205 (3.41%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	117/529 (22.12%)	26/205 (12.68%)
Back pain † 1	121/529 (22.87%)	28/205 (13.66%)
Bone pain † 1	55/529 (10.40%)	15/205 (7.32%)
Pain in extremity † 1	45/529 (8.51%)	12/205 (5.85%)
Nervous system disorders
Dizziness † 1	42/529 (7.94%)	9/205 (4.39%)
Headache † 1	36/529 (6.81%)	4/205 (1.95%)
Psychiatric disorders
Insomnia † 1	28/529 (5.29%)	9/205 (4.39%)
Renal and urinary disorders
Haematuria † 1	37/529 (6.99%)	8/205 (3.90%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	42/529 (7.94%)	13/205 (6.34%)
Dyspnoea † 1	50/529 (9.45%)	19/205 (9.27%)
Vascular disorders
Hypertension † 1	30/529 (5.67%)	12/205 (5.85%)
1 Term from vocabulary, MedDRA (23.1); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing.

Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.

Results Point of Contact

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: 862-778-8300
• EMail: Novartis.email@novartis.com

Publications of Results:

Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, Tagawa ST, Nordquist LT, Vaishampayan N, El-Haddad G, Park CH, Beer TM, Armour A, Perez-Contreras WJ, DeSilvio M, Kpamegan E, Gericke G, Messmann RA, Morris MJ, Krause BJ; VISION Investigators. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103. doi: 10.1056/NEJMoa2107322. Epub 2021 Jun 23.

Other Publications:

Iravani A, Violet J, Azad A, Hofman MS. Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies. Prostate Cancer Prostatic Dis. 2020 Mar;23(1):38-52. doi: 10.1038/s41391-019-0174-x. Epub 2019 Oct 8.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sundlov A, Sjogreen-Gleisner K. Peptide Receptor Radionuclide Therapy - Prospects for Personalised Treatment. Clin Oncol (R Coll Radiol). 2021 Feb;33(2):92-97. doi: 10.1016/j.clon.2020.10.020. Epub 2020 Nov 12.

• Responsible Party: Endocyte
• ClinicalTrials.gov Identifier: NCT03511664
• Other Study ID Numbers: PSMA-617-01; 2018-000459-41 ( EudraCT Number ); CAAA617A12301 ( Other Identifier: Novartis )
• First Submitted: April 13, 2018
• First Posted: April 30, 2018
• Results First Submitted: April 12, 2022
• Results First Posted: May 9, 2022
• Last Update Posted: August 11, 2022