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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT07047118




Registration number
NCT07047118
Ethics application status
Date submitted
20/05/2025
Date registered
2/07/2025
Date last updated
10/09/2025

Titles & IDs
Public title
A Study of JSB462 (Luxdegalutamide) Plus Lutetium (177Lu) Vipivotide Tetraxetan in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)
Scientific title
A Phase II, Randomized, Open-label, Multi-center Study of JSB462 (Luxdegalutamide) in Combination With Lutetium (177Lu) Vipivotide Tetraxetan in Adult Male Patients With PSMA-positive Metastatic Castration Resistant Prostate Cancer (mCRPC)
Secondary ID [1] 0 0
2024-520155-24-00
Secondary ID [2] 0 0
CJSB462B12201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Cancer, Castration-Resistant 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - JSB462
Treatment: Drugs - AAA617

Experimental: Arm 1 - JSB462 100 mg QD + AAA617 7.4 GBq Q6W

Experimental: Arm 2 - JSB462 300 mg QD + AAA617 7.4 GBq Q6W

Active comparator: Arm 3 - AAA617 7.4 GBq Q6W


Treatment: Drugs: JSB462
Administered orally, daily and continuously (100 mg or 300 mg QD) until disease progression per PCWG3-modified RECIST v1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision

Treatment: Drugs: AAA617
administered at 7.4 GBq intravenously every 6 weeks for up to 6 doses, unless there is disease progression per PCWG3-modified RECIST v1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Prostate Specific Antigen 50 (PSA50) Rate
Timepoint [1] 0 0
From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Primary outcome [2] 0 0
Incidence rate of adverse events (AEs)
Timepoint [2] 0 0
From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Primary outcome [3] 0 0
Number of participants with dose adjustments
Timepoint [3] 0 0
From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Primary outcome [4] 0 0
Duration of exposure to study treatment
Timepoint [4] 0 0
From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Secondary outcome [1] 0 0
Radiographic Progression Free Survival (rPFS)
Timepoint [1] 0 0
From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 41 months
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
From date of randomization until date of death from any cause, assessed up to approximately 41 months
Secondary outcome [3] 0 0
Incidence rate of adverse events (AEs)
Timepoint [3] 0 0
From date of randomization until date of death from any cause, assessed up to approximately 41 months
Secondary outcome [4] 0 0
Overall Response Rate (ORR)
Timepoint [4] 0 0
From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 41 months
Secondary outcome [5] 0 0
Disease Control Rate (DCR)
Timepoint [5] 0 0
From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 41 months
Secondary outcome [6] 0 0
Duration of Response (DOR)
Timepoint [6] 0 0
From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 41 months
Secondary outcome [7] 0 0
Time to Response (TTR)
Timepoint [7] 0 0
From date of randomization until date of first documented Complete Response (CR) or Partial Response (PR), assessed up to approximately 41 months
Secondary outcome [8] 0 0
Time to soft tissue progression (TTSTP)
Timepoint [8] 0 0
From date of randomization until date of soft tissue radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 41 months
Secondary outcome [9] 0 0
Prostate Specific Antigen 90 (PSA90) Rate
Timepoint [9] 0 0
From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Secondary outcome [10] 0 0
Prostate Specific Antigen 30 (PSA30) Rate
Timepoint [10] 0 0
From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Secondary outcome [11] 0 0
Prostate Specific Antigen 0 (PSA0) Rate
Timepoint [11] 0 0
From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Secondary outcome [12] 0 0
Duration of biochemical response (DBR)
Timepoint [12] 0 0
From date of date of first PSA50 response until date of PSA progression or death from any cause, assessed up to approximately 41 months
Secondary outcome [13] 0 0
Time to first symptomatic skeletal event (TTSSE)
Timepoint [13] 0 0
From randomization until the first occurrence of a new symptomatic bone fracture, spinal cord compression, tumor-related orthopedic surgery, radiation therapy for bone pain, or death, assessed up to 41 months.
Secondary outcome [14] 0 0
Plasma concentrations of JSB462 and plasma concentrations of its metabolite ARV-767
Timepoint [14] 0 0
Day 1 of Cycles 1 and 2: Pre-dose/0hour and Post-dose 4hour +/- 1hour. Day 1 of Cycles 3 to 6: Pre-dose/0hour. End of Treatment Visit (EOT): through study treatment discontinuation, an average of 24 months. 1 cycle = 28 days.
Secondary outcome [15] 0 0
Concentrations of AAA617 in blood over time and PK parameters from blood radioactivity data
Timepoint [15] 0 0
Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.
Secondary outcome [16] 0 0
Area under the AAA617 concentration-time curve from time zero to the time of last quantifiable concentration (AUClast)
Timepoint [16] 0 0
Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.
Secondary outcome [17] 0 0
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of AAA617
Timepoint [17] 0 0
Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.
Secondary outcome [18] 0 0
Observed maximum blood concentration (Cmax) of AAA617
Timepoint [18] 0 0
Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.
Secondary outcome [19] 0 0
Time of maximum observed blood concentration occurrence (Tmax) of AAA617
Timepoint [19] 0 0
Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.
Secondary outcome [20] 0 0
Terminal elimination half-life (T1/2) of AAA617
Timepoint [20] 0 0
Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.
Secondary outcome [21] 0 0
Total systemic clearance for intravenous administration (CL) of AAA617
Timepoint [21] 0 0
Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.
Secondary outcome [22] 0 0
Volume of distribution during the terminal phase following intravenous elimination (Vz) of AAA617
Timepoint [22] 0 0
Cycle 1: Day 1 (pre-dose/0hour, end of infusion (EOI), 1hour ±15minutes, 4hours ±30minutes), Day 2 (24hours ±2hours), Day 3 (48hours ±2hours), Day 8 (168hours ±12hours).Cycles 3 & 5: Day 1 (pre-dose/0hour, EOI), Day 3 (48hours ±2hours). 1 cycle=6 weeks.
Secondary outcome [23] 0 0
Radiation absorbed doses in organs and tumors for AAA617
Timepoint [23] 0 0
Cycle 1: Day 1 (1-4 hours), Day 2 (24 hours ±6 hours), Day 3 (48 hours ±6 hours), Day 8 (168 hours ±24 hours). Cycle 3: Day 1 (1-4 hours), Day 3 (48 hours ±6 hours). Cycle 5b (fit patients): Day 1 (1-4 hours), Day 3 (48 hours ±6 hours). 1 cycle=6 weeks.
Secondary outcome [24] 0 0
Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Timepoint [24] 0 0
From date of randomization until date of death from any cause, assessed up to approximately 41 months

Eligibility
Key inclusion criteria
Key

* Adult male participants with histologically and/or cytologically confirmed adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible.
* An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade =2.
* At least 1 bone or visceral metastatic lesion present on baseline CT, MRI, or bone scan imaging obtained =28 days prior to initiation of study treatment.
* Participants must be [68Ga]Ga-PSMA-11 PET/CT scan positive and eligible as determined by the sponsor's central reader.
* Participant must have prior exposure to at least one second generation ARPI in the metastatic/advanced setting.
* Previous treatment with a maximum of 2 taxane regimens is allowed.
* Participants eligible for PARPi and/or immune checkpoint inhibitor (per local testing and according to investigator's judgement) are eligible to participate if they have previous exposure to this(these) therapy(ies).

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment with any RLT (approved or investigational) is not allowed
* Prior treatment with a protein degrader compound that targets AR is not allowed

Other protocol-defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [2] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Nebraska
Country [2] 0 0
Israel
State/province [2] 0 0
Haifa
Country [3] 0 0
Israel
State/province [3] 0 0
Jerusalem
Country [4] 0 0
Singapore
State/province [4] 0 0
Singapore

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.