Study of Lutetium (177Lu) Vipivotide Tetraxetan in mCRPC Participants With Moderately and Severely Impaired and With Normal Renal Function

NCT06004661 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: CAAA617A122022023-503925-20-00
• Study Type: interventional
• Target: 20
• Locations: 5 countries
• Sites: 9

Brief Summary

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.

Conditions

Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Keywords

Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer; Prostate-specific membrane antigen; PSMA; Metastatic Castration-Resistant Prostate Cancer; mCRPC; Renal impairment; Moderately impaired renal function; Severely impaired renal function; Normal renal function; lutetium (177Lu) vipivotide tetraxetan; AAA617; Dosimetry; QTc prolongation; post marketing requirement

Outcome Measures

Primary Outcomes (12)

• Absorbed radiation dose in kidneys and selected organs

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  Dose modifications (dose interruptions and reductions) for AAA617 will be assessed and summarized using descriptive statistics.

  Up to 36 weeks

• Dose intensity for AAA617

  Dose intensity for AAA617 will be assessed and summarized using descriptive statistics.

  Up to 36 weeks

Secondary Outcomes (5)

• Relationship between drug concentrations and QTcF

  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)

  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)

  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

  From screening up to 1 year

• Potential impact of moderate and severe renal impairment on AAA617 urine PK

  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

Study Arms (1)

AAA617

EXPERIMENTAL

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.

Drug: AAA617; Drug: 68Ga-PSMA-11

Interventions

AAA617 DRUG

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

Also known as: Pluvicto, 177Lu-Lu-PSMA-617

AAA617

68Ga-PSMA-11 DRUG

Single intravenous dose of approximately 150 MBq

AAA617

Eligibility Criteria

• Age: 18 Years - 100 Years
• Gender Eligibility Details: Prostate cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Ga-PSMA-11 Positron emission tomography (PET)/CT scan positive, and eligible as determined by the sponsor's central reader.
• A castrate level of serum/plasma testosterone (\< 50 ng/dL or \< 1.7 nmol/L).
• 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)
• 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.
• 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

You may not qualify if:

• Previous treatment with PSMA-targeted radioligand therapy.
• 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.
• 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.
• 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.
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

Mount Sinai Hosp Med School

New York, New York, 10029, United States

RECRUITING

Novartis Investigative Site

Paris, 75014, France

RECRUITING

Novartis Investigative Site

Vandœuvre-lès-Nancy, 54511, France

RECRUITING

Novartis Investigative Site

Essen, 45147, Germany

RECRUITING

Novartis Investigative Site

München, 80377, Germany

RECRUITING

Novartis Investigative Site

Milan, 20141, Italy

RECRUITING

Novartis Investigative Site

Naples, 80131, Italy

RECRUITING

Novartis Investigative Site

Granada, Andalusia, 18014, Spain

RECRUITING

Novartis Investigative Site

El Palmar, Murcia, 30120, Spain

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Pluvicto; gallium 68 PSMA-11

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants confirmed for enrollment in IRT will be stratified in one of the three cohorts based on eGFR calculated (MDRD formula) at screening: * Cohort A: normal renal function eGFR \>= 90 mL/min/1.73m2, * Cohort B: moderate renal impairment eGFR \>= 30 to =\< 59 mL/min/1.73m2 * Cohort C: severe renal impairment eGFR \>= 15 to =\< 29 mL/min/1.73m2.

Study Record Dates

• First Submitted: June 29, 2023
• First Posted: August 22, 2023
• Study Start: April 4, 2024
• Primary Completion (Estimated): June 17, 2026
• Study Completion (Estimated): June 17, 2026
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1); IT (2); FR (2); DE (2); ES (2)