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

Official title

A Phase I, Open-label, Multi-center Study of Radiation Dosimetry, Safety, and Tolerability of Extended Lutetium (177Lu) Vipivotide Tetraxetan Treatment in Chemo-naïve Adults With Metastatic Castration-resistant Prostate Cancer

Overview

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).

Detailed description

The study includes screening period, treatment period, and a post-treatment follow-up period.

Screening Period: Approximately 106 participants will be enrolled to receive up to12 consecutive cycles of AAA617. Potential participants will be assessed for eligibility by verifying their baseline PSMA PET scan for mandatory confirmation of PSMA positivity prior to first cycle by local review.

Treatment Period: Eligible participants will be treated with up to 12 cycles of 7.4 GBq AAA617 intravenously every 6 weeks, until radiographic progression, toxicity leading to treatment discontinuation, death, loss to follow-up, or withdrawal of consent, whichever occurs first. During treatment period, all participants who complete the initial 6 cycles of AAA617 treatment will undergo an additional PSMA-PET scan after Cycle 6 to re-assess PSMA expression level and to reassess eligibility of participants to receive additional AAA617 treatment cycles.

Post-Treatment Follow-Up: All participants will undergo a PSMA-PET scan at end of treatment (EOT). The post-treatment follow-up period will consist of EOT; 42-days safety; EOT RLI; safety, survival and rPFS follow-up visits.

The planned duration of treatment period is up to 74 weeks with treatment given every 6 weeks. Participants may be discontinued from treatment earlier due to unacceptable toxicity or disease progression, and/or at the discretion of the Investigator or the participant.

Interventions

• Drug AAA617
  \[177Lu\]Lu-PSMA-617 will be administered as an intravenous infusion at a dose of 7.4 GBq (200mCi) (+/- 10%), every 6 weeks for up to 12 cycles.
• Drug Gonadotropin-releasing hormone (GnRH) analogues
  Anatomical Therapeutic Chemical \[ATC\] code L02AE
• Drug Gonadotropin-releasing hormone (GnRH) antagonists
  Degarelix, Relugolix

Primary outcome measures

• Time activity curves (TACs) and absorbed radiation dose of AAA617 in organs [Time frame: From Cycle 1 to Cycle 12; cycle = 42 days]
• 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]
• 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)]

Secondary outcome measures (12)

• Time activity curves (TACs) and absorbed radiation dose AAA617 in tumors [Time frame: For up to 12 cycles; cycle = 42 days]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• 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]
• Duration of response (DOR) [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]
• Radiographic Progressive free survival (rPFS) [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]

Eligibility criteria

Inclusion criteria

• Signed informed consent must be obtained prior to participation in the study.
• Participants must be adults ≥ 18 years of age.
• Participants must have an ECOG performance status ≤ 1.
• Participants must have histological confirmation of adenocarcinoma of the prostate.
• Participants must be PSMA-positive per 68Ga-PSMA PET/CT scans at baseline
• Participants must have a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L) either by pharmaceutical or surgical methods.
• Participants must have progressed only once on prior second generation ARPIs
• Documented progressive mCRPC
• Participants must have ≥ 1 metastatic lesion by conventional imaging that is present on screening/baseline CT, MRI, or bone scan
• Renal: eGFR ≥ 60 mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
• Participants must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies except alopecia.

Exclusion criteria

• Previous treatment with any of the following within 6 months of study enrollment: Strontium 89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation
• Any previous radioligand therapy.
• Prior treatment with cytotoxic chemotherapy for metastatic castration-resistant or metastatic hormone-sensitive prostate cancer (mHSPC) (e.g., taxanes, platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy or biological therapy \[including monoclonal antibodies\]. \[Note: Taxane exposure (maximum 6 cycles) in the adjuvant or neoadjuvant setting is allowed if 12 months have elapsed since completion of this adjuvant or neoadjuvant therapy. Prior treatment with sipuleucel-T is allowed\].
• Concurrent therapies: cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological, or investigational therapy
• History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature and/or clinically active significant cardiac disease
• Concurrent serious acute or chronic nephropathy and/or moderate to severe renal impairment as determined by the principal investigator.
• Diagnosed with other active malignancies that are expected to alter life expectancy or may interfere with disease assessment
• Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 14 weeks after stopping study treatment.
• Concurrent urinary outflow obstruction or unmanageable urinary incontinence
• History of somatic or psychiatric disease/condition that may interfere with the aims and assessments of the study.

Other protocol-defined inclusion/exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 7 centers

• Novartis Investigative Site — Cologne
• Novartis Investigative Site — Wuppertal
• Novartis Investigative Site — Aachen
• Novartis Investigative Site — Berlin
• Novartis Investigative Site — Essen
• Novartis Investigative Site — München
• Novartis Investigative Site — Rostock

United States · 5 centers

• University of California LA — Los Angeles
• Stanford University — Palo Alto
• Mayo Clinic Rochester — Rochester
• Wash U School of Medicine — St Louis
• Nebraska Cancer Specialists — Omaha

Spain · 3 centers

• Novartis Investigative Site — Santiago Compostela
• Novartis Investigative Site — Majadahonda
• Novartis Investigative Site — Barcelona

United Kingdom · 3 centers

• Novartis Investigative Site — Sutton
• Novartis Investigative Site — Birmingham
• Novartis Investigative Site — Glasgow

Switzerland · 2 centers

• Novartis Investigative Site — Bellinzona
• Novartis Investigative Site — Bern

Netherlands · 1 center

• Novartis Investigative Site — Nijmegen

Identifiers

NCT: NCT06531499 · CAAA617A12101 · 2024-512338-13

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗