A Study of Radiation Dosimetry, Safety, and Tolerability of Extended Lutetium (177Lu) Vipivotide Tetraxetan Treatment in Chemo-naïve Adults With Metastatic Castration-resistant Prostate Cancer: RADIOpharmaceutical DOSimetry Evaluation (RADIODOSE) Study

Time activity curves (TACs) and absorbed radiation dose of AAA617 in organs

Time frame · From Cycle 1 to Cycle 12; cycle = 42 days

Time activity curve (TAC) will be generated from the amount radioactivity in one given tissue. Time integrated activity coefficient and absorbed dose will be calculated

Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame · For up to 12 cycles in taxane-naive participants with progressive PSMA-positive mCRPC with nrmal kidney function or mild renal impairment; cycle = 42 days

The distribution of adverse events for Radioligand Therapy (RLT) 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. Adverse event monitoring should be continued for at least 42 days following the end of treatment (EOT) visit. Participants receiving the study treatment will continue to be followed for safety every 12 weeks during the long-term follow-up for selected adverse events

Percentage of participants with AAA617 dose reductions, interruptions and discontinuations

Time frame · Up to 42 (+7) days after last AAA617 dose administration (Safety Follow-up)

The assessment of tolerability will be based on the frequency of participants with dose interruptions, reductions, and study treatment discontinuations. Dose reduction will be based on the worst toxicity demonstrated at the last dose.

Time activity curves (TACs) and absorbed radiation dose AAA617 in tumors

Time frame · For up to 12 cycles; cycle = 42 days

Time activity curves (TACs) will be generated from the amount of radioactivity in one given tissue at a given moment. TACs will be fitted to mono- and bi-exponential curves. Time integrated activity coefficient and absorbed dose will be calculated.

Pharmacokinetic ( PK) concentration of AAA617 in blood over time

Time frame · Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11 and Cycle 12, cycle = 42 days

PK concentrations will be listed by patient and visit/sampling time point. The descriptive summary statistics will be provided by visit/sampling time point.

Pharmacokinetic (PK) parameter Cmax of AAA617 from blood radioactivity data

Time frame · Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11 and Cycle 12; cycle = 42 days

Derived PK parameter, Cmax will be listed by patient and visit. The descriptive summary statistics will be provided by visit. Cmax is the maximum drug concentration after dosing.

PK parameter Tmax of AAA617 from blood radioactivity data

Time frame · Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11 and Cycle 12; cycle = 42 days

Derived PK parameter Tmax, will be listed by patient and visit. The descriptive summary statistics will be provided by visit. Tmax is the time to reach the maximum concentration.

PK parameter AUC of AAA617 from blood radioactivity data

Time frame · Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11 and Cycle 12; cycle = 42 days

Derived PK parameter AUC will be listed by patient and visit. The descriptive summary statistics will be provided by visit. AUC: Area under the concentration-time curve.

PK parameter CL of AAA617 from blood radioactivity data

Time frame · Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11 and Cycle 12; cycle = 42 days

Derived PK parameter CL will be listed by patient and visit. The descriptive summary statistics will be provided by visit. Clearance (CL): Rate at which the body eliminates the drug.

PK parameter VZ of AAA617 from blood radioactivity data

Time frame · Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11 and Cycle 12; cycle = 42 days

Derived PK parameter Vz will be listed by patient and visit. The descriptive summary statistics will be provided by visit. Vz: volume of distribution during the terminal phase (Vz).

PK parameter terminal T1/2 of AAA617 from blood radioactivity data

Time frame · Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11, and Cycle 12; cycle = 42 days

Derived PK parameter terminal T1/2 will be listed by patient and visit. The descriptive summary statistics will be provided by visit. T1/2: Terminal half life.

Overall response rate (ORR)

Time frame · From first patient first visit (FPFV) to end of study, until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 58 months

ORR is defined as the proportion of participants with BOR of confirmed CR or PR per investigator assessment and according to Prostate Cancer Working Group 3 (PCWG3) modified-RECIST v1.1.

Disease Control rate (DCR)

Time frame · From first patient first visit (FPFV) to end of study, until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 58 months

DCR is defined as the percentage of CR, PR, stable disease or non-CR/non-progressive disease (PD) per investigator assessment and according to PCWG3 modified-RECIST v1.1 assessment in soft tissue, lymph node, and visceral lesions.