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Studie av Lutetium (177Lu) Vipivotide Tetraxetan hos mCRPC-deltagare med måttligt och gravt nedsatt och med normal njurfunktion

6 november 2026 uppdaterad av: Novartis Pharmaceuticals

En öppen dosimetri-, biodistributions-, tolerabilitets- och säkerhetsstudie av lutetium (177Lu) Vipivotidtetraxetan hos deltagare med progressiv PSMA-positiv metastatisk kastrationsresistent prostatacancer (mCRPC) med måttligt och allvarligt nedsatt och med normal njurfunktion.

This study will address health authorities' requests to determine whether moderate and severe renal impairment have an impact on the biodistribution, dosimetry and safety of lutetium (177Lu) vipivotide tetraxetan (AAA617) administered to participants with progressive PSMA-positive metastatic castration-resistant prostate cancer. The study will also characterize the risk of QT prolongation of AAA617 in this participant population.

Studieöversikt

Status

Aktiv, inte rekryterande

Betingelser

Intervention / Behandling

Detaljerad beskrivning

This open-label, non-randomized, multicenter, single arm phase II study in mCRPC participants aims to better characterize the safety and tolerability of AAA617 in participants with moderate and severe renal impairment compared with normal renal function. Since both severe and moderate renal impairment have very low incidence within mCRPC participant population compared to participants with normal renal function, the enrollment will occur in parallel for the 3 cohorts; participants will be stratified in one of the three cohorts (A:normal, B: moderate or C: severe) based on their eGFR at screening.

All participants will undergo a 68Ga-PSMA-11 PET/CT scan at screening to confirm PSMA positivity.

Participants will receive a dose of 7.4 GBq (±10%) of AAA617 once every 6 weeks for a planned 6 cycles for cohorts A and B and 3 cycles for cohort C. Based on the emerging safety data and if the investigators deem the participant is still benefiting from study drug, 3 additional cycles may be administered for cohort C participants.

After treatment period, participants will be asked to join a long term follow up (LTFU) study to monitor their safety up to 10 years after the 1st dose of AAA617. In case of the LTFU study is not available at the time of end of treatment period (safety follow-up visit), participants will continue in Long Term Follow-up period in this study for up to one year until they can roll over into the separate LTFU study.

The primary outcome will be to determine the effect of radiation absorption in kidney and other organs at risk as well as the concentration in blood and derived PK parameters from radioactivity in blood in PSMA-positive mCRPC participants with moderate and severe renal impairment. In addition, the study will assess the relationship between drug concentrations and QTcF.

Approximately 20 participants will be enrolled in the study with at least 6 evaluable participants per cohort.

Studietyp

Interventionell

Inskrivning (Faktisk)

23

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Frankrike
      • Paris, Frankrike, 75014
        • Novartis Investigative Site
      • Vandœuvre-lès-Nancy, Frankrike, 54511
        • Novartis Investigative Site
  • Förenta staterna
    • New York
      • New York, New York, Förenta staterna, 10029
        • Mount Sinai Hosp Med School
  • Italien
      • Naples, Italien, 80131
        • Novartis Investigative Site
    • MI
      • Milan, MI, Italien, 20141
        • Novartis Investigative Site
  • Spanien
    • Andalusia
      • Granada, Andalusia, Spanien, 18014
        • Novartis Investigative Site
    • Murcia
      • El Palmar, Murcia, Spanien, 30120
        • Novartis Investigative Site
  • Tyskland
      • Essen, Tyskland, 45147
        • Novartis Investigative Site
      • München, Tyskland, 80377
        • Novartis Investigative Site

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 100 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Manlig

Beskrivning

Key Inclusion Criteria:

  1. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

  2. 68Ga-PSMA-11 Positron emission tomography (PET)/CT scan positive, and eligible as determined by the sponsor's central reader.

  3. A castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).

  4. Documented progressive mCRPC will be based on at least 1 of the following criteria:

    • Serum/plasma Prostate-Specific Antigen (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
    • 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.
    • Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (2+2 PCWG3 criteria)

  5. Documented stable chronic renal disease without evidence of further deterioration in renal function (stable chronic renal disease is defined as no significant change in renal function within 4 weeks prior to study entry.

  6. Kidney function based on eGFR by Modification of Diet in Renal Disease (MDRD) equation:

    • Normal renal function: participants with eGFR >= 90 mL/min/1.73m2
    • Moderate renal impairment: participants with eGFR >= 30 to =< 59 mL/min/1.73m2
    • Severe renal impairment: participants with eGFR >= 15 to =< 29 mL/min/1.73m2

Key Exclusion Criteria:

  1. Previous treatment with PSMA-targeted radioligand therapy.

  2. Previous treatment with any of the following within 6 months of enrollment confirmation: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation.

  3. Use of agents known to prolong the QT interval from start of screening to end of Cycle 1, unless they can be permanently discontinued for the duration of study.

  4. Current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, any level of urinary obstruction requiring indwelling/condom catheters. Participants with postrenal impairment, like obstructions, retroperitoneal fibrosis (eg after prostatectomy) must be excluded or first resolved to ≤ Grade 1.

  5. History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants participating in the study such as:

    • Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second- or third-degree AV block without a pacemaker.
    • History of familial long QT syndrome or known family history of Torsades de Pointe.
    • Resting heart rate (12 lead ECG) <60 bpm

Other protocol-defined inclusion/exclusion criteria may apply.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: AAA617

Participants will receive a dose of 7.4 GBq (200 mCi) ± 10% of AAA617 which will be administered once every 6 weeks (1 cycle) for up to 6 cycles if enrolled in Cohorts A or B. Participants with severe renal impairment (in cohort C) will receive a dose of 7.4 GBq of AAA617 for up to 3 cycles of treatment. Based on the emerging safety data and if the investigators deem the participant is still benefiting from study drug, 3 additional cycles may be administered for Cohort C participants.
Läkemedel: AAA617

Administered intravenously once every cycles (1 cycle = 6 weeks)

Andra namn:
  • Pluvicto
  • 177Lu-Lu-PSMA-617
Läkemedel: 68Ga-PSMA-11

Single intravenous dose of approximately 150 MBq

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Absorbed radiation dose in kidneys and selected organs
Tidsram: Up to 36 weeks

The absorbed dose in kidneys and selected organs will be summarized with descriptive statistics.
Up to 36 weeks
Concentrations of AAA617 in blood over time
Tidsram: Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Blood concentration of [177Lu]Lu-PSMA-617 will be summarized with descriptive statistics.
Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks
Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of 177Lu-PSMA-617
Tidsram: Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.
Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks
Time of maximum observed drug concentration occurrence (Tmax) of 177Lu-PSMA-617
Tidsram: Cycle (C) 1 Day (D) 1 (2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle = 6 weeks

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
Cycle (C) 1 Day (D) 1 (2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle = 6 weeks
Observed maximum plasma concentration (Cmax) of 177Lu-PSMA-617
Tidsram: Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks
Terminal elimination half-life (T^1/2) of 177Lu-PSMA-617
Tidsram: Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. The half-live will be listed and summarized using descriptive statistics
Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of 177Lu-PSMA-617
Tidsram: Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC(0-inf) will be listed and summarized using descriptive statistics.
Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks
Total systemic clearance for intravenous administration (CL) of 177Lu-PSMA-617
Tidsram: Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.
Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks
Volume of distribution during the terminal phase following intravenous elimination (Vz) of 177Lu-PSMA-617
Tidsram: Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.
Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks
Change from baseline in eGFR
Tidsram: at screening and at every visit, assessed up to 1 year after last treatment

Change from baseline of eGFR will be summarized for each post-dose (post-baseline) timepoint. The summary includes table with descriptive statistics at baseline, post-baseline time points and change from baseline to post-baseline timepoints.
at screening and at every visit, assessed up to 1 year after last treatment
Dose modifications for AAA617
Tidsram: Up to 36 weeks

Dose modifications (dose interruptions and reductions) for AAA617 will be assessed and summarized using descriptive statistics.
Up to 36 weeks
Dose intensity for AAA617
Tidsram: Up to 36 weeks

Dose intensity for AAA617 will be assessed and summarized using descriptive statistics.
Up to 36 weeks

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Relationship between drug concentrations and QTcF
Tidsram: During Cycle 1 at predose, End of Injection (EoI), 20 minutes (min), 60 min, 2 hours (h), 4h and 24h post EoI. Cycle=6 weeks

The relationship between 177Lu-PSMA-617 plasma concentrations and ΔQTcF will be investigated using a linear mixed-effects modeling approach with ΔQTcF as the dependent variable, time-matched 177Lu-PSMA-617 plasma concentration as the explanatory variable, centered baseline QTcF (i.e., baseline QTcF for individual patient minus the population mean baseline QTcF for all patients) as an additional covariate, a fixed intercept, and a random intercept and slope per patient, when applicable (Garnett et al1).
During Cycle 1 at predose, End of Injection (EoI), 20 minutes (min), 60 min, 2 hours (h), 4h and 24h post EoI. Cycle=6 weeks
Overall Response Rate (ORR)
Tidsram: From the date of 1st dose until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to approximately 36 weeks

Objective response rate (ORR) (CR + PR) as measured by PCWG3-modified RECIST v1.1 response in soft tissue, lymph node and visceral lesions as per local review and according to PCWG3-modified RECIST v1.1. CR and PR must be confirmed by repeat assessments that should be performed not less than 4 weeks after the criteria for response are first met.
From the date of 1st dose until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to approximately 36 weeks
Disease Control Rate (DCR)
Tidsram: From the date of 1st dose until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to approximately 36 weeks

Disease Control Rate (DCR) (CR + PR + stable disease [SD]) as measured by PCWG3-modified RECIST v1.1 response in soft tissue, lymph node and visceral lesions. DCR will be analyzed using the same analytical conventions as ORR.
From the date of 1st dose until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to approximately 36 weeks
PSA50 response
Tidsram: From screening up to 1 year

PSA50 response is defined as the proportion of participants who have a >= 50% decrease in PSA from baseline that is confirmed by a second (the next) PSA measurement >= 4 weeks later
From screening up to 1 year
Potential impact of moderate and severe renal impairment on AAA617 urine PK
Tidsram: Cycle 1 Day 1: end of infusion to 2 hours, 2 hours to 4 hours, 4 hours to 24 hours, 24 hours to 48 hours, 48 hours to 72 hours post infusion. Cycle = 6 weeks

Derived urine PK parameters from urine PK radioactivity data (The volume of each urine collection will be measured and the radioactivity concentration (KBq/mL) determined in order to calculate the total radioactivity excreted from the body from the start of infusion until 72h.)
Cycle 1 Day 1: end of infusion to 2 hours, 2 hours to 4 hours, 4 hours to 24 hours, 24 hours to 48 hours, 48 hours to 72 hours post infusion. Cycle = 6 weeks

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Novartis Pharmaceuticals

Utredare

  • Studierektor: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

4 april 2024

Primärt slutförande (Beräknad)

6 november 2026

Avslutad studie (Beräknad)

6 november 2026

Studieregistreringsdatum

Först inskickad

29 juni 2023

Först inskickad som uppfyllde QC-kriterierna

16 augusti 2023

Första postat (Faktisk)

22 augusti 2023

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

9 november 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

6 november 2026

Senast verifierad

1 november 2026

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • CAAA617A12202
  • 2023-503925-20-00 (Registeridentifierare: EU CT Number)
  • 2023 (U.S.S. NIH-anslag/kontrakt)

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

JA

IPD-planbeskrivning

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Ja

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

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