NEPC Study: An Exploratory Safety and Efficacy Study With PSMA, SSTR2 and GRPR Targeted Radioligand Therapy in Metastatic Neuroendocrine Prostate Cancer.

Number/extent of lesions with at least a moderate uptake of any of the Radioligand Imaging (RLI)

Time frame · Baseline (baseline imaging is performed during the 42 day screening period)

Number/extent of lesions with at least a moderate update of any of the RLIs according to visual assessment scoring scale on each corresponding targeted PET/CT scan based on blinded independent central review (BICR) assessment.

Percentage changes in quantitative PET parameters.

Time frame · Post-Baseline (from date of baseline imaging scans to post-baseline scans, at least 6 weeks after receiving the first cycle of radioligand treatment)

Percentage changes in quantitative PET/CT parameters (SUVmax, SUVmean, SUVpeak, target-positive Tumor Volume (target -TV), Total Lesion (target (TL-target)\] and changes in number of target-positive lesions (as per visual assessment) on each corresponding target PET/CT based on BICR.

Overall Response Rate (ORR)

Time frame · From date of assignment to one of the treatment arms until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 31 months

Overall Response Rate (ORR) is defined as the proportion of participants with the best overall response (BOR) of confirmed complete response (CR) or partial response (PR) based on Prostate Cancer Working Group 3 (PCWG3) modified-RECIST v1.1.

Disease Control Rate (DCR)

Time frame · From date of assignment to one of the treatment arms until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 31 months

Disease Control Rate (DCR) is defined as the proportion of participants with BOR of CR, PR, stable disease (SD), or non-CR/non-PD based on PCWG3 modified-RECIST v1.1.

Duration of response (DOR)

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 approximately 31 months

Duration of response (DOR) is defined as the time (in months) from the date of the first confirmed response (CR or PR) to the date of first documented progression according to PCWG3 modified-RECIST v1.1 or death due to any cause, among participants with a confirmed response.

Radiographic Progression-free Survival (rPFS)

Time frame · From date of assignment to one of the treatment arms until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 31 months

Radiographic Progression-free Survival (rPFS) is defined as the time from the date of first dose of study treatment to the date of first documented radiographic progression (as assessed by the local investigator and using PCWG3 modified-RECIST v1.1 criteria) or death due to any cause.

Proportion of participants with a decline in PSA level

Time frame · Baseline, Cycle 1 Day 1 (each cycle is 42 days), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, End Of Treatment, 6 weeks after End of Treatment

The PSA analysis will investigate the proportion of participants with a decline in PSA level from baseline to each visit.

Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) for Radioligand Therapy (RLT)

Time frame · Up to 42 days after last dose administration (Safety Follow-up) and every 12 weeks until end of long term follow up (Long-term FU) for selected AEs and SAEs

The distribution of adverse events for Radioligand Therapy (RLT) will be done via the analysis of frequencies for Adverse Events (AEs) and Serious Adverse Events (SAEs) through the monitoring of relevant clinical and laboratory safety parameters. Adverse event monitoring should be continued for at least 42 days following the end of treatment (EOT) visit. Participants receiving the study treatment \[68Ga\]Ga-DOTA-TATE/\[177Lu\]Lu-PSMA-617 or \[177Lu\]Lu-NeoB will continue to be followed for safety every 12 weeks during the long-term follow-up for selected adverse events.

Dose modifications for [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB

Time frame · Up to 42 days after last dose administration (Safety Follow-up)

Dose modifications (dose interruptions, dose discontinuations and reductions) for \[177Lu\]Lu-PSMA-617, \[177Lu\]Lu-DOTA-TATE and \[177Lu\]Lu-NeoB will be assessed and summarized using descriptive statistics.

Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) for Radioligand Imaging (RLI)

Time frame · Continuously from informed consent for the first 6 weeks and selected AEs and SAEs thereafter

The distribution of adverse events for Radioligand Imaging (RLI) will be done via the analysis of frequencies for Adverse Event (AEs) and Serious Adverse Event (SAEs) through the monitoring of relevant clinical and laboratory safety parameters.

Blood radioactivity concentration of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE, [177Lu]Lu-NeoB)

Time frame · Cycle 1 Day 1 (each cycle is 42 days) pre-dose, post-dose/end of infusion (EOI) and then 0.5 hrs, 2 hrs, 4 hrs, 6 hrs 24 hrs, 48 hrs, 168 hrs post EOI. Cycle 3 Day 1 EOI, 1 hr, 48 hrs post EOI. Cycle 5 Day 1 EOI, and then 1 hr, 48 hrs post EOI.

Data will be listed by participant and visit/sampling time point. Descriptive summary statistics will be provided by visit/sampling time point and treatment arm including the frequency (n, %) of concentrations below the lower limit of quantification (LLOQ) and reported as zero.

Blood mass concentration of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE, [177Lu]Lu-NeoB)

Time frame · Cycle 1 Day 1 (each cycle is 42 days) pre-dose, post-dose/end of infusion (EOI) and then 0.5 hrs, 2 hr, 4 hr, 6 hrs, 24 hrs, 48 hrs 168 hrs post EOI. Cycle 3 Day 1 EOI, 1 hr, 48 hrs post EOI. Cycle 5 Day 1 EOI, and then 1 hr, 48 hrs post EOI.

Data will be listed by participant and visit/sampling time point. Descriptive summary statistics will be provided by visit/sampling time point and treatment arm including the frequency (n, %) of concentrations below the lower limit of quantification (LLOQ) and reported as zero.