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
NCT Number: NCT06531499
Acronym: RADIODOSE
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Metastatic Castration-Resistant Prostate Cancer
Interventions: DRUG: AAA617|DRUG: Gonadotropin-releasing hormone (GnRH) analogues|DRUG: Gonadotropin-releasing hormone (GnRH) antagonists
Sponsor: Novartis Pharmaceuticals
Sex: MALE
Age: ADULT, OLDER_ADULT
Enrollment: 106
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-10-30
Completion Date: 2028-01-21

Summary:
The purpose of the study is to assess and evaluate dosimetry, safety, and tolerability following administration of up to 12 cycles of (177Lu) vipivotide tetraxetan (also referred to as \[177Lu\]Lu-PSMA-617 or 177Lu-PSMA-617 and hereafter identified as AAA617) in taxane-naïve adult participants with PSMA-positive mCRPC who progressed on a prior ARPI treatment with normal renal function or mild renal impairment (eGFR ≥ 60ml/min).

Primary Outcome Measures: Time activity curves (TACs) and absorbed radiation dose of AAA617 in organs, 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, From Cycle 1 to Cycle 12; cycle = 42 days|Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), 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, 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|Percentage of participants with AAA617 dose reductions, interruptions and discontinuations, 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., Up to 42 (+7) days after last AAA617 dose administration (Safety Follow-up)
Secondary Outcome Measures: Time activity curves (TACs) and absorbed radiation dose AAA617 in tumors, 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., For up to 12 cycles; cycle = 42 days|Pharmacokinetic ( PK) concentration of AAA617 in blood over time, PK concentrations will be listed by patient and visit/sampling time point. The descriptive summary statistics will be provided by visit/sampling time point., Cycle1, Cycle 4, Cycle 7, Cycle 9, and Cycle 12, cycle = 42 days|Pharmacokinetic (PK) parameter Cmax of AAA617 from blood radioactivity data, 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., Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 9 and Cycle 12; cycle = 42 days|PK parameter Tmax of AAA617 from blood radioactivity data, 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., Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 9 and Cycle 12; cycle = 42 days|PK parameter AUC of AAA617 from blood radioactivity data, 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., Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 9 and Cycle 12; cycle = 42 days|PK parameter CL of AAA617 from blood radioactivity data, 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., Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 9 and Cycle 12; cycle = 42 days|PK parameter VZ of AAA617 from blood radioactivity data, 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)., Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 9 and Cycle 12; cycle = 42 days|PK parameter terminal T1/2 of AAA617 from blood radioactivity data, 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., Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 9 and Cycle 12; cycle = 42 days|Overall response rate (ORR), 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., 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|Disease Control rate (DCR), 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., 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|Duration of response (DOR), DOR is defined as the duration of time between the date of the first documented BOR (CR or PR) per investigator assessment according to PCWG3 modified-RECIST v1.1 and the date of first documented progression or death due to any cause., 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|Radiographic Progressive free survival (rPFS), rPFS defined as the time from the date of first dose of study treatment to the date of the first documented radiographic disease progression as assessed by investigator and PCWG3 modified-RECIST v1.1 criteria or death due to any cause, whichever occurs first., 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|Prostate specific antigen (PSA) response, PSA response is defined as percentage of participants who achieve any decrease from baseline that is confirmed by a second PSA measurement ≥4 weeks. Participants with any decrease in PSA will also be summarized by visit., Baseline, (Cycle (C), Day (D)) C1D1, C2D1, C3D1, C4D1, C5D1, C6D1, C6D42, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, End Of Treatment (EOT), 6 weeks after EOT, every 12 weeks after EOT up to 12 months; each cycle = 42 days|Overall survival (OS), Overall survival is defined as the time from the first dose of study treatment to death due to any cause., Cycle 1 to death event, approx. 5 years, (cycle = 42 days)|Duration of exposure to AAA617 and dose intensity, Duration of exposure:

Dose intensity is computed as the ratio of actual cumulative dose received and actual duration of exposure., during treatment period (74 weeks)