Prostate Cancer
Conditions
Keywords
Metastatic castration-resistant prostate cancer, mCRPC, 177Lu-PSMA-617, PSMA-617, PSMA-11, radioligand therapy
Brief summary
The primary objective of this study was to compare the two alternate primary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) in patients with progressive prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who received 177Lu-PSMA-617 in addition to best supportive/best standard of care (BSC/BSoC) versus patients treated with best supportive/best standard of care alone.
Detailed description
The study for each participant consisted of a Screening period, a Treatment period and a Follow-up period. Sub-study A dosimetry, PK and ECG sub-study was conducted in a non-randomized cohort (AAA617+BSC/BSoC) of 30 patients at sites in Germany to provide a more complete assessment of the safety aspects of AAA617. Aside from additional assessments to collect data for dosimetry, PK, urinary metabolites and ECG, patients in the sub-study were screened for eligibility, treated and followed up similarly to the AAA617+BSC/BSoC (investigational arm) patients in the main study. Screening and randomization: During the screening period of up to 28 days before starting randomized treatment, each participant was assessed for PSMA positivity by gallium (68Ga) gozetotide imaging PET/scan per the pre-defined read rules, by the Sponsor's central reader. Only patients with PSMA-positive metastatic PC and meeting all other inclusion/exclusion criteria were randomized in a 2:1 ratio to receive either 177Lu-PSMA-617 plus BSC/BSoC or BSC/BSoC only. Randomized patients were stratified on the following factors: LDH level (=\< or \> 260 UI/L), presence of liver metastases (Yes or No), eastern cooperative oncology group (ECOG) score (0-1 or 2) and inclusion of NAAD in the BSC/BSoC (at time of randomization (Yes or No)). Protocol- specified BSC/BSoC for each patient was initiated by the investigating physician prior to patient randomization and maintained throughout the study. On-study changes to BSC/BSoC were allowed and at the discretion of the investigating physician. Randomized treatment: Randomized treatment in this study refers to AAA617+BSC/BSoC (investigational arm) and BSC/BSoC only (control arm). For the sub-study, study treatment refers to AAA617+BSC/BSoC (also referred to as the investigational arm), as no randomization occurred in the sub-study. When discussing aspects of the study which are applicable to both the main and sub-study, the term 'randomized treatment' will be used throughout this document. The term 'study treatment' will be used only when specifically referring to the sub-study. Patients randomized to the investigational arm began AAA617 dosing within 28 days of randomization. These patients received BSC/BSoC and 7.4 GBq (+/-10%) AAA617 once every 6 weeks (+/- 1 week) for a maximum of 6 cycles. After the Cycle 4 treatment and prior to Cycle 5 treatment, the Investigator had to determine if: * The patient showed evidence of response (i.e. radiological, PSA, clinical benefit) * The patient had signs of residual disease on CT with contrast/MRI or bone scan * The patient had shown good tolerance to the AAA617 treatment If the patient met all of the criteria above and agreed to continue with additional treatment of AAA617 the investigator could administer a further 2 cycles. A maximum of 6 cycles of radioligand therapy was allowed. If the patient did not meet any of the criteria or did not agree to additional AAA617 treatment, then no additional doses of AAA617 were administered after Cycle 4. After the last cycle of AAA617, patients continued BSC/BSoC alone, as long as the investigator felt they were clinically benefiting or until they required a treatment regimen not allowed in this study. For both treatment arms, the cycle duration for Cycle 1-6 was 6 weeks and for Cycle 7 and beyond, 12 weeks. From Cycle 7 onwards, all patients from both treatment arms only received BSC/BSoC. End of treatment: An End of Treatment (EOT) visit was scheduled approximately 30 days after the last dose of AAA617 or the date of the BSC/BSoC end of treatment decision (whichever occurred later), but before the initiation of subsequent anti-cancer treatment, outside of what was allowed on study. Once a patient discontinued the randomized treatment part of the study for any reason, an EOT visit was scheduled. Long-term follow-up: Patients on the active part of the study at the time of the final analysis of OS had an EOT visit at the next planned visit after implementation of V5.0/5.1 of the protocol and moved into long-term follow-up, unless they specifically withdrew consent from long-term follow-up of the study. Patients who consented to be followed for long-term status updates, entered the long-term follow-up period after the EOT visit. The long-term follow-up period included the collection of rPFS (if the patient discontinued for reasons other than radiographic progression), OS, information about new treatments along with the patient's response to these treatments, AE assessment, and results of hematology and chemistry testing. During the follow-up, patients were contacted every 3 months (+/-1 month) via phone, email, or letter until a long-term follow-up study became available, until death or until withdrawal of consent, whichever occurred first.
Interventions
DRUG177Lu-PSMA-617
Administered intravenously once every 6 weeks (1 cycle) for a maximum of 6 cycles. After 4 cycles, patients were assessed for (1) evidence of response, (2) residual disease, and (3) tolerance to 177Lu-PSMA-617. If all 3 assessments were met the patient might received an additional 2 cycles of 177Lu-PSMA-617.
Best supportive/best standard of care as defined by the local investigator
Sponsors
Endocyte
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants in the Main Study were randomized in a 2:1 ratio to receive either 177Lu-PSMA-617 plus BSC/BSoC or BSC/BSoC only. The sub-study was conducted in a non-randomized cohort (AAA617+ BSC/BSoC)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients must have the ability to understand and sign an approved informed consent form (ICF). 2. Patients must have the ability to understand and comply with all protocol requirements. 3. Patients must be \>= 18 years of age. 4. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 5. Patients must have a life expectancy \>6 months. 6. Patients must have histological, pathological, and/or cytological confirmation of prostate cancer. 7. Patients must be 68Ga-PSMA-11 Positron Emission Tomography (PET)/Computed Tomography (CT) scan positive, and eligible as determined by the sponsor's central reader. 8. Patients must have a castrate level of serum/plasma testosterone (\<50 ng/dL or \<1.7 nmol/L). 9. Patients must have received at least one NAAD (such as enzalutamide and/or abiraterone). 10. Patients must have been previously treated with at least 1, but no more than 2 previous taxane regimens. A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. If a patient has received only 1 taxane regimen, the patient is eligible if: a. The patient's physician deems him unsuitable to receive a second taxane regimen (e.g. frailty assessed by geriatric or health status evaluation, intolerance, etc.). 11. Patients must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria: 1. Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL. 2. Soft-tissue progression defined as an increase \>= 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions. 3. Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (2+2 PCWG3 criteria, Scher et al 2016). 12. Patients must have \>= 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging obtained =\< 28 days prior to beginning study therapy. 13. Patients must have recovered to =\< Grade 2 from all clinically significant toxicities related to prior therapies (i.e. prior chemotherapy, radiation, immunotherapy, etc.). 14. Patients must have adequate organ function: a. Bone marrow reserve: * White blood cell (WBC) count \>= 2.5 x 10\^9/L (2.5 x 10\^9/L is equivalent to 2.5 x 10\^3/μL and 2.5 x K/μL and 2.5 x 10\^3/cumm and 2500/μL) OR absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (1.5 x 10\^9/L is equivalent to 1.5 x 10\^3/μL and 1.5 x K/μL and 1.5 x 10\^3/cumm and 1500/μL) * Platelets \>= 100 x 10\^9/L (100 x 10\^9/L is equivalent to 100 x 10\^3/μL and 100 x K/μL and 100 x 10\^3/cumm and 100,000/μL) * Hemoglobin \>= 9 g/dL (9 g/dL is equivalent to 90 g/L and 5.59 mmol/L) b. Hepatic: * Total bilirubin =\< 1.5 x the institutional upper limit of normal (ULN). For patients with known Gilbert's Syndrome =\< 3 x ULN is permitted * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =\< 3.0 x ULN OR =\< 5.0 x ULN for patients with liver metastases c. Renal: * Serum/plasma creatinine =\< 1.5 x ULN or creatinine clearance \>= 50 mL/min 15. Albumin \>3.0 g/dL (3.0 g/dL is equivalent to 30 g/L) \[Inclusion #16 has been removed\] 17\. HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes are included in this trial. 18\. For patients who have partners of childbearing potential: Partner and/or patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principle investigator during the study and for 6 months after last study drug administration. 19\. The best standard of care/ best supportive care options planned for this patient: 1. Are allowed by the protocol 2. Have been agreed to by the treating investigator and patient 3. Allow for the management of the patient without 177Lu-PSMA-617
Exclusion criteria
1. Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed. 2. Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy \[including monoclonal antibodies\]) within 28 days prior to day of randomization. 3. Any investigational agents within 28 days prior to day of randomization. 4. Known hypersensitivity to the components of the study therapy or its analogs. 5. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy. 6. Transfusion for the sole purpose of making a subject eligible for study inclusion. 7. Patients with a history of Central Nervous System (CNS) metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast). 8. A superscan as seen in the baseline bone scan. 9. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression. 10. Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation. 11. Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, patients with a prior history of malignancy that has been adequately treated and who have been disease free for more than 3 years are eligible, as are patients with adequately treated non-melanoma skin cancer, superficial bladder cancer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Progression-free Survival (rPFS) | From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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. |
| Overall Survival (OS) | From date of randomization until date of death from any cause, assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021) and up to 66 months (Final Analysis cut-off date = 14-Dec-2023) | 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. Final OS was analyzed at the time of Primary analysis (Primary Analysis cut-off date = 27-Jan-2021) and an updated descriptive analysis of OS was re-run at the time of final analysis (Final Analysis cut-off date 14-Dec-2023). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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. |
| Duration of Response (DOR) | 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 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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 to First Symptomatic Skeletal Event (SSE) | From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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). |
| Progression-free Survival (PFS) | From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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. |
| Best Percentage Change From Baseline in Prostate-specific Antigen (PSA) Level | From date of randomization till 30 days safety fup, assessed up to approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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). |
| Percentage of Participants Achieving Prostate-specific Antigen (PSA) Response | From date of randomization till 30 days safety fup, assessed up to approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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. |
| Prostate-specific Antigen 80 (PSA80) Response | From date of randomization till 30 days safety fup, assessed up to approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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. |
| Duration of PSA Response | From date of first documented PSA response till 30 days safety fup, assessed up to approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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. |
| Best Percentage Change From Baseline in Alkaline Phosphatase (ALP) Level | From date of randomization till 30 days safety fup, assessed up to approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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). |
| Best Percentage Change From Baseline in Lactate Dehydrogenase (LDH) Level | From date of randomization till 30 days safety fup, assessed up to approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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 to Worsening in BPI-SF Pain Intensity Scale | From date of randomization until date of End of Treatment (EoT), assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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 to Improvement After Worsening in BPI-SF Pain Intensity Scale | From date of randomization until date of End of Treatment (EoT), assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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 to Worsening in BPI-SF Pain Interference Scale | From date of randomization until date of End of Treatment (EoT), assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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. |
| Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | From randomization till 30 days safety follow-up, assessed up to 66 months (Final Analysis cut-off date = 14-Dec-2023) | In the Main Study, randomized treatment refers to the investigational arm (AAA617+BSC/BSoC) and the control arm (BSC/BSoC). In the sub-study, study treatment refers to the investigational arm (AAA617+BSC/BSoC) without randomization: 1. A randomized treatment-emergent adverse event (TEAE) is any adverse event that occurs from the start of randomized treatment to 30 days after the last administration of randomized treatment or prior to the initiation of subsequent anticancer treatment. 2. A study treatment-emergent adverse event (TEAE) is any adverse event that occurs from the start of study treatment to 30 days after the last administration of study treatment or prior to the initiation of subsequent anticancer treatment. The distribution of randomized/study treatment-emergent adverse events (TEAEs) was done via the analysis of frequencies for TEAEs and Serious Adverse Event (TESAEs), through the monitoring of relevant clinical and laboratory safety parameters. |
| Time to Worsening in BPI-SF Worst Pain Intensity Scale (Time to Disease Related Pain) | From date of randomization until date of End of Treatment (EoT), assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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. |
| Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | 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) | 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. |
| Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | 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) | 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 to Worsening in FACT-P Total Score | From date of randomization until date of End of Treatment (EoT), assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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. |
| Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | 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) | 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 to Worsening in EQ-5D-5L Utility Score | From date of randomization until date of End of Treatment (EoT), assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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. |
| Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | 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) | 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. |
| Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | 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) | 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. |
| Number of Participants Hospitalized as In-patient | From date of randomization till 30 days safety fup, assessed up to approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021) | The number of hospitalizations (yes/no) (admitted as in-patient) was collected as part of the hospital admission for health economic evaluations. |
| Duration of Time in Hospital Following 177Lu-PSMA-617 Administration | From date of randomization till 30 days safety fup, assessed up to approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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). |
| Concomitant Drug Use for Health Economics Analysis | From date of randomization till 30 days safety fup, assessed up to approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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. |
| Therapeutic Interventions for Health Economics Analysis | From date of randomization till 30 days safety fup, assessed up to approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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 to Improvement After Worsening in BPI-SF Pain Interference Scale | From date of randomization until date of End of Treatment (EoT), assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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. |
| Overall Response Rate (ORR) | From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021) | 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 evaluable disease at baseline per central review assessment. |
Countries
Belgium, Canada, Denmark, France, Germany, Netherlands, Puerto Rico, Sweden, United Kingdom, United States
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).
Participants by arm
| Arm | Count |
|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) 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 | 551 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator | 280 |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) non-randomized cohort (AAA617+ BS/BSOC) at sites in Germany to provide a more complete assessment of the safety aspects of AAA617. Patients were treated and followed up similarly to the AAA617+BSC/BSOC (investigational arm) patients in the main study | 30 |
| Total | 861 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 457 | 201 | 21 |
| Overall Study | Lost to Follow-up | 8 | 5 | 0 |
| Overall Study | Other protocol pre-specified reasons for discontinuation | 15 | 4 | 2 |
| Overall Study | Patient non-compliance | 1 | 0 | 0 |
| Overall Study | Physician Decision | 2 | 1 | 0 |
| Overall Study | Withdrew consent | 40 | 63 | 3 |
Baseline characteristics
| Characteristic | Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Total |
|---|---|---|---|---|
| Age, Customized ≥ 65-84 years | 398 Participants | 214 Participants | 18 Participants | 630 Participants |
| Age, Customized < 65 years | 145 Participants | 60 Participants | 12 Participants | 217 Participants |
| Age, Customized ≥ 85 years | 8 Participants | 6 Participants | 0 Participants | 14 Participants |
| Race/Ethnicity, Customized Asian | 9 Participants | 11 Participants | 0 Participants | 20 Participants |
| Race/Ethnicity, Customized Black or African American | 34 Participants | 21 Participants | 0 Participants | 55 Participants |
| Race/Ethnicity, Customized Missing | 20 Participants | 13 Participants | 0 Participants | 33 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 486 Participants | 235 Participants | 30 Participants | 751 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 551 Participants | 280 Participants | 30 Participants | 861 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 68 / 551 | 19 / 280 | 5 / 30 | 389 / 461 | 182 / 186 | 16 / 25 |
| other Total, other adverse events | 502 / 529 | 151 / 205 | 28 / 30 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 195 / 529 | 58 / 205 | 9 / 30 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Overall Survival (OS)
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. Final OS was analyzed at the time of Primary analysis (Primary Analysis cut-off date = 27-Jan-2021) and an updated descriptive analysis of OS was re-run at the time of final analysis (Final Analysis cut-off date 14-Dec-2023).
Time frame: From date of randomization until date of death from any cause, assessed up to 32 months (Primary Analysis cut-off date = 27-Jan-2021) and up to 66 months (Final Analysis cut-off date = 14-Dec-2023)
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Overall Survival (OS) | Final OS analysis | 15.3 Months |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Overall Survival (OS) | Primary OS Analysis | 15.3 Months |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Overall Survival (OS) | Final OS analysis | 11.5 Months |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Overall Survival (OS) | Primary OS Analysis | 11.3 Months |
Comparison: Primary OS Analysisp-value: <0.00195% CI: [0.52, 0.74]Log Rank
Comparison: Final OS analysis95% CI: [0.58, 0.81]
Primary
Radiographic Progression-free Survival (rPFS)
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 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS Full Analysis Set (PFS-FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Radiographic Progression-free Survival (rPFS) | 8.7 Months |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Radiographic Progression-free Survival (rPFS) | 3.4 Months |
p-value: <0.00199.2% CI: [0.29, 0.57]Log Rank
Secondary
Best Percentage Change From Baseline in Alkaline Phosphatase (ALP) Level
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 approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS Full Analysis Set (PFS-FAS). Only participants with evaluable post-baseline and baseline samples were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Best Percentage Change From Baseline in Alkaline Phosphatase (ALP) Level | -14.4 Percentage change | Standard Deviation 46.3 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Best Percentage Change From Baseline in Alkaline Phosphatase (ALP) Level | 0.6 Percentage change | Standard Deviation 33.8 |
Secondary
Best Percentage Change From Baseline in Lactate Dehydrogenase (LDH) Level
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 approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS Full Analysis Set (PFS-FAS). Only participants with evaluable post-baseline and baseline samples were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Best Percentage Change From Baseline in Lactate Dehydrogenase (LDH) Level | -23.1 Percentage change | Standard Deviation 23.8 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Best Percentage Change From Baseline in Lactate Dehydrogenase (LDH) Level | -9.2 Percentage change | Standard Deviation 28.2 |
Secondary
Best Percentage Change From Baseline in Prostate-specific Antigen (PSA) Level
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 approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS Full Analysis Set (PFS-FAS). Only participants with evaluable post-baseline and baseline samples were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Best Percentage Change From Baseline in Prostate-specific Antigen (PSA) Level | -20.9 Percentage change | Standard Deviation 142.6 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Best Percentage Change From Baseline in Prostate-specific Antigen (PSA) Level | 50.4 Percentage change | Standard Deviation 118.4 |
Secondary
Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 2, Week 1, Day 1 change from BL | -0.59 Score on a scale | Standard Deviation 2.037 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 7, Week 1, Day 1 change from BL | -0.48 Score on a scale | Standard Deviation 2.011 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 8, Week 1, Day 1 change from BL | -0.18 Score on a scale | Standard Deviation 1.759 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 9, Week 1, Day 1 change from BL | -0.70 Score on a scale | Standard Deviation 2.157 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 10, Week 1, Day 1 change from BL | 0.02 Score on a scale | Standard Deviation 1.513 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 11, Week 1, Day 1 change from BL | -0.40 Score on a scale | Standard Deviation 0.956 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 12, Week 1, Day 1 change from BL | -1.00 Score on a scale | Standard Deviation 0.354 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 13, Week 1, Day 1 change from BL | -0.75 Score on a scale | — |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | End of Treatment (EoT) change from BL | 0.46 Score on a scale | Standard Deviation 2.415 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 3, Week 1, Day 1 change from BL | -0.62 Score on a scale | Standard Deviation 1.924 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 5, Week 1, Day 1 change from BL | -0.49 Score on a scale | Standard Deviation 1.957 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 6, Week 1, Day 1 change from BL | -0.41 Score on a scale | Standard Deviation 1.897 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 4, Week 1, Day 1 change from BL | -0.42 Score on a scale | Standard Deviation 2.017 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 2, Week 1, Day 1 change from BL | 0.21 Score on a scale | Standard Deviation 2.404 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 3, Week 1, Day 1 change from BL | 0.02 Score on a scale | Standard Deviation 2.033 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 9, Week 1, Day 1 change from BL | 0.13 Score on a scale | Standard Deviation 1.78 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 4, Week 1, Day 1 change from BL | 0.26 Score on a scale | Standard Deviation 2.383 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 5, Week 1, Day 1 change from BL | 0.55 Score on a scale | Standard Deviation 3.144 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 6, Week 1, Day 1 change from BL | 0.10 Score on a scale | Standard Deviation 2.74 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 11, Week 1, Day 1 change from BL | 0.75 Score on a scale | Standard Deviation 1.768 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 7, Week 1, Day 1 change from BL | -0.32 Score on a scale | Standard Deviation 1.585 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 10, Week 1, Day 1 change from BL | 0.50 Score on a scale | Standard Deviation 1.768 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | Cycle 8, Week 1, Day 1 change from BL | -1.10 Score on a scale | Standard Deviation 2.205 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Intensity Scale | End of Treatment (EoT) change from BL | 0.50 Score on a scale | Standard Deviation 2.405 |
Secondary
Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 10, Week 1, Day 1 change from BL | 0.62 Score on a scale | Standard Deviation 2.141 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 4, Week 1, Day 1 change from BL | -0.33 Score on a scale | Standard Deviation 2.249 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 5, Week 1, Day 1 change from BL | -0.32 Score on a scale | Standard Deviation 2.223 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 6, Week 1, Day 1 change from BL | -0.28 Score on a scale | Standard Deviation 2.166 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 7, Week 1, Day 1 change from BL | -0.22 Score on a scale | Standard Deviation 1.882 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 8, Week 1, Day 1 change from BL | 0.18 Score on a scale | Standard Deviation 1.926 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 9, Week 1, Day 1 change from BL | -0.15 Score on a scale | Standard Deviation 1.751 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 11, Week 1, Day 1 change from BL | -0.06 Score on a scale | Standard Deviation 1.334 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 12, Week 1, Day 1 change from BL | -0.89 Score on a scale | Standard Deviation 0.914 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 13, Week 1, Day 1 change from BL | -0.43 Score on a scale | — |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | End of Treatment (EoT) change from BL | 0.73 Score on a scale | Standard Deviation 2.756 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 2, Week 1, Day 1 change from BL | -0.40 Score on a scale | Standard Deviation 2.167 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 3, Week 1, Day 1 change from BL | -0.35 Score on a scale | Standard Deviation 2.348 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 2, Week 1, Day 1 change from BL | 0.58 Score on a scale | Standard Deviation 2.7 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | End of Treatment (EoT) change from BL | 0.29 Score on a scale | Standard Deviation 2.385 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 3, Week 1, Day 1 change from BL | -0.15 Score on a scale | Standard Deviation 2.216 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 8, Week 1, Day 1 change from BL | -0.26 Score on a scale | Standard Deviation 1.291 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 4, Week 1, Day 1 change from BL | 0.21 Score on a scale | Standard Deviation 2.762 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 11, Week 1, Day 1 change from BL | 0.36 Score on a scale | Standard Deviation 4.748 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 5, Week 1, Day 1 change from BL | 0.52 Score on a scale | Standard Deviation 3.48 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 9, Week 1, Day 1 change from BL | 0.12 Score on a scale | Standard Deviation 1.667 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 6, Week 1, Day 1 change from BL | 0.49 Score on a scale | Standard Deviation 3.354 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 10, Week 1, Day 1 change from BL | 1.50 Score on a scale | Standard Deviation 1.313 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in BPI-SF (Brief-Pain Inventory - Short Form) Pain Interference Scale | Cycle 7, Week 1, Day 1 change from BL | 0.06 Score on a scale | Standard Deviation 2.57 |
Secondary
Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 2, Week 1, Day 1 change from BL | 3.6 Score on a scale | Standard Deviation 16.63 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 4, Week 1, Day 1 change from BL | 5.4 Score on a scale | Standard Deviation 15.93 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 5, Week 1, Day 1 change from BL | 4.0 Score on a scale | Standard Deviation 16.24 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 6, Week 1, Day 1 change from BL | 4.1 Score on a scale | Standard Deviation 15.22 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 7, Week 1, Day 1 change from BL | 4.9 Score on a scale | Standard Deviation 16.47 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 8, Week 1, Day 1 change from BL | 3.8 Score on a scale | Standard Deviation 15.87 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 9, Week 1, Day 1 change from BL | 3.8 Score on a scale | Standard Deviation 14.22 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 10, Week 1, Day 1 change from BL | 0.0 Score on a scale | Standard Deviation 18.27 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 11, Week 1, Day 1 change from BL | -0.8 Score on a scale | Standard Deviation 20.99 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 12, Week 1, Day 1 change from BL | 10.3 Score on a scale | Standard Deviation 12.11 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 13, Week 1, Day 1 change from BL | 30.0 Score on a scale | — |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | End of Treatment (EoT) change from BL | -9.4 Score on a scale | Standard Deviation 21.64 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 3, Week 1, Day 1 change from BL | 3.8 Score on a scale | Standard Deviation 17.48 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 2, Week 1, Day 1 change from BL | -7.2 Score on a scale | Standard Deviation 17.85 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 10, Week 1, Day 1 change from BL | 0.2 Score on a scale | Standard Deviation 14.14 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 3, Week 1, Day 1 change from BL | -2.6 Score on a scale | Standard Deviation 14 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 8, Week 1, Day 1 change from BL | -13.0 Score on a scale | Standard Deviation 32.76 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 4, Week 1, Day 1 change from BL | -1.3 Score on a scale | Standard Deviation 18.4 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | End of Treatment (EoT) change from BL | -10.4 Score on a scale | Standard Deviation 18.59 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 5, Week 1, Day 1 change from BL | -5.9 Score on a scale | Standard Deviation 27.83 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 9, Week 1, Day 1 change from BL | 6.9 Score on a scale | Standard Deviation 5.92 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 6, Week 1, Day 1 change from BL | -5.0 Score on a scale | Standard Deviation 26.87 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 11, Week 1, Day 1 change from BL | 8.2 Score on a scale | Standard Deviation 33.71 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in FACT-P (Functional Assessment of Cancer Therapy - Prostate) Total Score | Cycle 7, Week 1, Day 1 change from BL | -2.9 Score on a scale | Standard Deviation 17.89 |
Secondary
Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 2, Week 1, Day 1 change from BL | 1.8 Score on a scale | Standard Deviation 19.98 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 4, Week 1, Day 1 change from BL | 2.8 Score on a scale | Standard Deviation 19.18 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 5, Week 1, Day 1 change from BL | 4.0 Score on a scale | Standard Deviation 17.3 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 6, Week 1, Day 1 change from BL | 2.1 Score on a scale | Standard Deviation 19.61 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 7, Week 1, Day 1 change from BL | 3.6 Score on a scale | Standard Deviation 20.64 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 8, Week 1, Day 1 change from BL | 0.6 Score on a scale | Standard Deviation 17.18 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 10, Week 1, Day 1 change from BL | 2.9 Score on a scale | Standard Deviation 13.97 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 11, Week 1, Day 1 change from BL | 5.8 Score on a scale | Standard Deviation 10.33 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 12, Week 1, Day 1 change from BL | 4.5 Score on a scale | Standard Deviation 13.03 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 13, Week 1, Day 1 change from BL | -5.0 Score on a scale | — |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | End of Treatment (EoT) change from BL | -8.9 Score on a scale | Standard Deviation 22.07 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 9, Week 1, Day 1 change from BL | 0.1 Score on a scale | Standard Deviation 19.68 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 3, Week 1, Day 1 change from BL | 1.4 Score on a scale | Standard Deviation 19.82 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 2, Week 1, Day 1 change from BL | -7.2 Score on a scale | Standard Deviation 20.31 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 11, Week 1, Day 1 change from BL | -9.0 Score on a scale | Standard Deviation 28.28 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 3, Week 1, Day 1 change from BL | -3.8 Score on a scale | Standard Deviation 21.5 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 8, Week 1, Day 1 change from BL | 13.8 Score on a scale | Standard Deviation 16.6 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 4, Week 1, Day 1 change from BL | -1.7 Score on a scale | Standard Deviation 18.73 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 9, Week 1, Day 1 change from BL | 6.3 Score on a scale | Standard Deviation 20.82 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 5, Week 1, Day 1 change from BL | -8.5 Score on a scale | Standard Deviation 28.88 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 10, Week 1, Day 1 change from BL | -8.0 Score on a scale | Standard Deviation 2.83 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 6, Week 1, Day 1 change from BL | 3.2 Score on a scale | Standard Deviation 19.43 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | End of Treatment (EoT) change from BL | -10.1 Score on a scale | Standard Deviation 21.49 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) EQ-VAS | Cycle 7, Week 1, Day 1 change from BL | 5.9 Score on a scale | Standard Deviation 12.79 |
Secondary
Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 2, Week 1, Day 1 change from BL | 0.0221 Score on a scale | Standard Deviation 0.17693 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 4, Week 1, Day 1 change from BL | 0.0292 Score on a scale | Standard Deviation 0.17713 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 5, Week 1, Day 1 change from BL | 0.0398 Score on a scale | Standard Deviation 0.16827 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 6, Week 1, Day 1 change from BL | 0.0342 Score on a scale | Standard Deviation 0.1795 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 7, Week 1, Day 1 change from BL | 0.0252 Score on a scale | Standard Deviation 0.16127 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 8, Week 1, Day 1 change from BL | 0.0285 Score on a scale | Standard Deviation 0.18017 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 9, Week 1, Day 1 change from BL | 0.0100 Score on a scale | Standard Deviation 0.17447 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 10, Week 1, Day 1 change from BL | 0.0134 Score on a scale | Standard Deviation 0.15764 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 11, Week 1, Day 1 change from BL | 0.0464 Score on a scale | Standard Deviation 0.16858 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 12, Week 1, Day 1 change from BL | 0.1118 Score on a scale | Standard Deviation 0.13833 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 13, Week 1, Day 1 change from BL | 0.0640 Score on a scale | — |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | End of Treatment (EoT) change from BL | -0.0939 Score on a scale | Standard Deviation 0.22698 |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 3, Week 1, Day 1 change from BL | 0.0297 Score on a scale | Standard Deviation 0.18817 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 2, Week 1, Day 1 change from BL | -0.0897 Score on a scale | Standard Deviation 0.24973 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 10, Week 1, Day 1 change from BL | -0.0655 Score on a scale | Standard Deviation 0.09263 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 3, Week 1, Day 1 change from BL | -0.0331 Score on a scale | Standard Deviation 0.14155 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 8, Week 1, Day 1 change from BL | -0.0296 Score on a scale | Standard Deviation 0.14964 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 4, Week 1, Day 1 change from BL | -0.0818 Score on a scale | Standard Deviation 0.23752 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | End of Treatment (EoT) change from BL | -0.0900 Score on a scale | Standard Deviation 0.21223 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 5, Week 1, Day 1 change from BL | -0.0673 Score on a scale | Standard Deviation 0.28633 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 9, Week 1, Day 1 change from BL | 0.0087 Score on a scale | Standard Deviation 0.08167 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 6, Week 1, Day 1 change from BL | -0.0110 Score on a scale | Standard Deviation 0.17842 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 11, Week 1, Day 1 change from BL | 0.0250 Score on a scale | Standard Deviation 0.1994 |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Change From Baseline in the European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score | Cycle 7, Week 1, Day 1 change from BL | -0.0088 Score on a scale | Standard Deviation 0.09081 |
Secondary
Concomitant Drug Use for Health Economics Analysis
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 approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS Full Analysis Set (PFS-FAS)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Bisphosphonates | Yes | 169 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Bisphosphonates | No | 216 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Corticosteroids | Yes | 246 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Corticosteroids | No | 139 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Antifungals | Yes | 1 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Antifungals | No | 384 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Erythropoietin Stimulating Agents | Yes | 8 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Erythropoietin Stimulating Agents | No | 377 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Granulocyte macrophage colony-stimulating factor | Yes | 7 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Granulocyte macrophage colony-stimulating factor | No | 378 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Novel Androgen Axis Drugs | Yes | 188 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Novel Androgen Axis Drugs | No | 197 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Antiemetics | Yes | 232 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Antiemetics | No | 153 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Opioid analgesics | Yes | 199 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Concomitant Drug Use for Health Economics Analysis | Opioid analgesics | No | 186 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Opioid analgesics | No | 100 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Bisphosphonates | Yes | 88 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Granulocyte macrophage colony-stimulating factor | Yes | 3 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Bisphosphonates | No | 108 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Antiemetics | Yes | 45 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Corticosteroids | Yes | 113 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Granulocyte macrophage colony-stimulating factor | No | 193 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Corticosteroids | No | 83 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Opioid analgesics | Yes | 96 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Antifungals | Yes | 4 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Novel Androgen Axis Drugs | Yes | 115 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Antifungals | No | 192 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Antiemetics | No | 151 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Erythropoietin Stimulating Agents | Yes | 2 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Novel Androgen Axis Drugs | No | 81 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Concomitant Drug Use for Health Economics Analysis | Erythropoietin Stimulating Agents | No | 194 Participants |
Secondary
Disease Control Rate (DCR)
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 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: Response Evaluable Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Disease Control Rate (DCR) | 284 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Disease Control Rate (DCR) | 80 Participants |
p-value: <0.00195% CI: [3.18, 10.55]Chi-squared
Secondary
Duration of PSA Response
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 approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS Full Analysis Set (PFS-FAS). Only participants with PSA progression were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Duration of PSA Response | 8.9 Months |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Duration of PSA Response | 4.4 Months |
Secondary
Duration of Response (DOR)
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 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Duration of Response (DOR) | 9.8 Months |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Duration of Response (DOR) | 10.6 Months |
Secondary
Duration of Time in Hospital Following 177Lu-PSMA-617 Administration
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 approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS Full Analysis Set (PFS-FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Duration of Time in Hospital Following 177Lu-PSMA-617 Administration | 28.25 Hours | Standard Deviation 46.578 |
Secondary
Number of Participants Hospitalized as In-patient
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 approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS Full Analysis Set (PFS-FAS)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants Hospitalized as In-patient | Yes | 157 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants Hospitalized as In-patient | No | 228 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Number of Participants Hospitalized as In-patient | Yes | 59 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Number of Participants Hospitalized as In-patient | No | 137 Participants |
Secondary
Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE)
In the Main Study, randomized treatment refers to the investigational arm (AAA617+BSC/BSoC) and the control arm (BSC/BSoC). In the sub-study, study treatment refers to the investigational arm (AAA617+BSC/BSoC) without randomization: 1. A randomized treatment-emergent adverse event (TEAE) is any adverse event that occurs from the start of randomized treatment to 30 days after the last administration of randomized treatment or prior to the initiation of subsequent anticancer treatment. 2. A study treatment-emergent adverse event (TEAE) is any adverse event that occurs from the start of study treatment to 30 days after the last administration of study treatment or prior to the initiation of subsequent anticancer treatment. The distribution of randomized/study treatment-emergent adverse events (TEAEs) was done via the analysis of frequencies for 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 66 months (Final Analysis cut-off date = 14-Dec-2023)
Population: FAS Safety Analysis Set. A patient with multiple grades for an AE is only counted under the maximum grade. Drug-related is related to any study drug (177Lu-PSMA-617 or BSC/BSoC). Study treatment refers to 177Lu-PSMA-617+BSC/BSoC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Drug-related TEAE | 451 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to reduction of BSC/BSoC | 17 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Drug-related grade 3/4/5 TEAE | 152 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE | 518 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to interruption of 177Lu-PSMA-617 | 85 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Serious TEAE | 195 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Grade 3/4/5 TEAE | 284 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to interruption of BSC/BSoC | 50 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to reduction of 177Lu-PSMA-617 | 30 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to discontinuation of 177Lu-PSMA-617 | 63 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to discontinuation of BSC/BSoC | 47 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Fatal TEAE | 19 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Serious Drug-related TEAE | 51 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Grade 3/4/5 TEAE | 79 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Fatal TEAE | 6 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to reduction of BSC/BSoC | 7 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to interruption of 177Lu-PSMA-617 | 2 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to interruption of BSC/BSoC | 14 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Serious Drug-related TEAE | 5 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to discontinuation of 177Lu-PSMA-617 | 1 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE | 170 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Serious TEAE | 58 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to discontinuation of BSC/BSoC | 16 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Drug-related grade 3/4/5 TEAE | 8 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to reduction of 177Lu-PSMA-617 | 0 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Drug-related TEAE | 59 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Grade 3/4/5 TEAE | 11 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Drug-related TEAE | 19 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to reduction of 177Lu-PSMA-617 | 2 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to reduction of BSC/BSoC | 1 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to interruption of 177Lu-PSMA-617 | 4 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to interruption of BSC/BSoC | 1 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to discontinuation of BSC/BSoC | 0 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Fatal TEAE | 2 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Serious Drug-related TEAE | 2 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Drug-related grade 3/4/5 TEAE | 6 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE leading to discontinuation of 177Lu-PSMA-617 | 2 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | TEAE | 30 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Number of Participants With Randomized/Study Treatment-emergent Adverse Events (TEAE) | Serious TEAE | 9 Participants |
Secondary
Overall Response Rate (ORR)
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 evaluable 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 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: Response Evaluable Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Overall Response Rate (ORR) | 95 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Overall Response Rate (ORR) | 2 Participants |
p-value: <0.00195% CI: [6.05, 103.24]Chi-squared
Secondary
Percentage of Participants Achieving Prostate-specific Antigen (PSA) Response
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 approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS Full Analysis Set (PFS-FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Percentage of Participants Achieving Prostate-specific Antigen (PSA) Response | 46.0 Percentage of participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Percentage of Participants Achieving Prostate-specific Antigen (PSA) Response | 7.1 Percentage of participants |
p-value: <0.00195% CI: [6.3, 20]Chi-squared
Secondary
Progression-free Survival (PFS)
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 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS Full Analysis Set (PFS-FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Progression-free Survival (PFS) | 5.9 Months |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Progression-free Survival (PFS) | 2.4 Months |
p-value: <0.00195% CI: [0.24, 0.38]Log Rank
Secondary
Prostate-specific Antigen 80 (PSA80) Response
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 approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS Full Analysis Set (PFS-FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Prostate-specific Antigen 80 (PSA80) Response | 33.0 Percentage of participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Prostate-specific Antigen 80 (PSA80) Response | 2.0 Percentage of participants |
p-value: <0.00195% CI: [8.6, 65.1]Chi-squared
Secondary
Therapeutic Interventions for Health Economics Analysis
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 approximately 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS Full Analysis Set (PFS-FAS)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Therapeutic Interventions for Health Economics Analysis | Local external beam therapy | Yes | 63 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Therapeutic Interventions for Health Economics Analysis | Local external beam therapy | No | 322 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Therapeutic Interventions for Health Economics Analysis | Blood transfusion | Yes | 74 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Therapeutic Interventions for Health Economics Analysis | Blood transfusion | No | 311 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Therapeutic Interventions for Health Economics Analysis | Blood transfusion | No | 183 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Therapeutic Interventions for Health Economics Analysis | Local external beam therapy | Yes | 37 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Therapeutic Interventions for Health Economics Analysis | Blood transfusion | Yes | 13 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Therapeutic Interventions for Health Economics Analysis | Local external beam therapy | No | 159 Participants |
Secondary
Time to First Symptomatic Skeletal Event (SSE)
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 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS Full Analysis Set (PFS-FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Time to First Symptomatic Skeletal Event (SSE) | 11.5 Months |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Time to First Symptomatic Skeletal Event (SSE) | 6.8 Months |
p-value: <0.00195% CI: [0.4, 0.62]Log Rank
Secondary
Time to Improvement After Worsening in BPI-SF Pain Intensity Scale
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 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS-Full analysis set. Only participants with evaluable events were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Time to Improvement After Worsening in BPI-SF Pain Intensity Scale | 2.8 Months |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Time to Improvement After Worsening in BPI-SF Pain Intensity Scale | 4.2 Months |
Secondary
Time to Improvement After Worsening in BPI-SF Pain Interference Scale
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 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS-Full analysis set. Only participants with evaluable events were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Time to Improvement After Worsening in BPI-SF Pain Interference Scale | 3.0 Months |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Time to Improvement After Worsening in BPI-SF Pain Interference Scale | 2.8 Months |
Secondary
Time to Worsening in BPI-SF Pain Intensity Scale
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 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS-Full analysis set. Only participants with evaluable events were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Time to Worsening in BPI-SF Pain Intensity Scale | 5.9 Months |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Time to Worsening in BPI-SF Pain Intensity Scale | 2.2 Months |
Secondary
Time to Worsening in BPI-SF Pain Interference Scale
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 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS-Full analysis set. Only participants with evaluable events were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Time to Worsening in BPI-SF Pain Interference Scale | 5.0 Months |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Time to Worsening in BPI-SF Pain Interference Scale | 2.3 Months |
Secondary
Time to Worsening in BPI-SF Worst Pain Intensity Scale (Time to Disease Related Pain)
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 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS-Full analysis set. Only participants with evaluable events were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Time to Worsening in BPI-SF Worst Pain Intensity Scale (Time to Disease Related Pain) | 5.0 Months |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Time to Worsening in BPI-SF Worst Pain Intensity Scale (Time to Disease Related Pain) | 2.0 Months |
Secondary
Time to Worsening in EQ-5D-5L Utility Score
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 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS-Full analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Time to Worsening in EQ-5D-5L Utility Score | 1.0 Months |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Time to Worsening in EQ-5D-5L Utility Score | 0.5 Months |
Secondary
Time to Worsening in FACT-P Total Score
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 32 months (Primary Analysis cut-off date = 27-Jan-2021)
Population: PFS-Full analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | Time to Worsening in FACT-P Total Score | 5.7 Months |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | Time to Worsening in FACT-P Total Score | 2.2 Months |
Post Hoc
All Collected Deaths
Pre-treatment deaths were collected from day of participant's informed consent to the day before first dose of study medication. On-treatment deaths were collected from first dose of study medication to 30 days after last dose of study medication (on-treatment), up to approximately 43 months. Deaths were collected in the post treatment survival follow up from 31 days after last dose of study medication until the end of the study, up to approximately 66 months. These are not considered AEs
Time frame: Pre-treatment deaths: Up to 28 days prior to treatment. On-treatment deaths: Up to approximately 43 months. Post-treatment deaths: Up to approximately 66 months
Population: Full Analysis Set (FAS) and the participants included in the sub-study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | All Collected Deaths | Pre-treatment deaths | 0 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | All Collected Deaths | On-treatment deaths | 68 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | All Collected Deaths | Post-treatment deaths | 389 Participants |
| Main Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | All Collected Deaths | All deaths | 457 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | All Collected Deaths | All deaths | 201 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | All Collected Deaths | Pre-treatment deaths | 0 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | All Collected Deaths | Post-treatment deaths | 182 Participants |
| Main Study: Best Supportive/Best Standard of Care (BS/BSOC) Alone | All Collected Deaths | On-treatment deaths | 19 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | All Collected Deaths | All deaths | 21 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | All Collected Deaths | On-treatment deaths | 5 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | All Collected Deaths | Post-treatment deaths | 16 Participants |
| Sub Study: 177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC) | All Collected Deaths | Pre-treatment deaths | 0 Participants |