Prostatic Cancer, Castration-ResistantPhase 2NCT07047118
A Study of JSB462 (Luxdegalutamide) Plus Lutetium (177Lu) Vipivotide Tetraxetan in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)
A Phase 2 study testing JSB462 and AAA617 in people with Prostatic Cancer, Castration-Resistant, run by Novartis Pharmaceuticals at 44 sites in 15 countries.
Trial summary
This Phase II study aims to evaluate the efficacy and safety of the combination of JSB462 (also known as luxdegalutamide) at 100 mg and 300 mg QD doses + lutetium (177Lu) vipivotide tetraxetan (hereafter referred as AAA617) compared with AAA617 (control) in participants with metastatic Castration Resistant Prostate… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostatic Cancer, Castration-Resistant
- What is being tested?
- JSB462 and AAA617
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 138 participants
- Where
- 44 sitesin 15 countries
- Study dates
- 3 Jul 2025to 14 May 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
44 sites in 15 countries.
44 sites in 15 countries
United States10 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Rocky Mountain Cancer Centers
Denver, Colorado, 80218
City of Hope National Medical
Duarte, California, 91010
Indiana University
Indianapolis, Indiana, 46202
Yale University School Of Medicine
New Haven, Connecticut, 06520
NYU Laura and Isaac Perlmutter Cancer Center
New York, New York, 10016
XCancer Omaha LLC
Omaha, Nebraska, 68130
Univ of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232
Urology San Antonio
San Antonio, Texas, 78229
Providence Saint Johns Health Ctr
Santa Monica, California, 90404
Israel6 sites
Novartis Investigative Site
Afula, 1834111
Novartis Investigative Site
Beersheba, 8457108
Novartis Investigative Site
Haifa, 3109601
Novartis Investigative Site
Jerusalem, 9103102
Novartis Investigative Site
Petah Tikva, 4941492
Novartis Investigative Site
Ramat Gan, 5265601
Spain4 sites
Novartis Investigative Site
Barcelona, 08035
Novartis Investigative Site
El Palmar, Murcia, 30120
Novartis Investigative Site
Granada, Andalusia, 18014
Novartis Investigative Site
Seville, 41013
Australia3 sites
Novartis Investigative Site
Adelaide, South Australia, 5000
Novartis Investigative Site
Darlinghurst, New South Wales, 2010
Novartis Investigative Site
Melbourne, Victoria, 3004
Austria3 sites
Novartis Investigative Site
Innsbruck, Tyrol, 6020
Novartis Investigative Site
Linz, 4020
Novartis Investigative Site
Vienna, 1090
France3 sites
Novartis Investigative Site
Brest, 29200
Novartis Investigative Site
Marseille, 13273
Novartis Investigative Site
Tours, 37044
Canada2 sites
Novartis Investigative Site
Burnaby, British Columbia, V5G 4P3
Novartis Investigative Site
Montreal, Quebec, H3T 1E2
China2 sites
Novartis Investigative Site
Beijing, 100034
Novartis Investigative Site
Beijing, 100036
Germany2 sites
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Rostock, 18057
Italy2 sites
Novartis Investigative Site
Genova, GE, 16132
Novartis Investigative Site
Roma, RM, 00128
Netherlands2 sites
Novartis Investigative Site
Hoofddorp, 2134 TM
Novartis Investigative Site
Nijmegen, Gerlderland, 6532 SZ
South Korea2 sites
Novartis Investigative Site
Seoul, 03722
Novartis Investigative Site
Seoul, 05505
About this study
Official 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)
This Phase II study aims to evaluate the efficacy and safety of the combination of JSB462 (also known as luxdegalutamide) at 100 mg and 300 mg QD doses + lutetium (177Lu) vipivotide tetraxetan (hereafter referred as AAA617) compared with AAA617 (control) in participants with metastatic Castration Resistant Prostate Cancer (mCRPC) with prior exposure to at least 1 Androgen Receptor Pathway Inhibitor (ARPI) and 0-2 taxane regimens and to select the recommended dose of the combination for phase III. Towards that end, the totality of the efficacy, safety, tolerability and pharmacokinetic (PK) data from participants randomized in the study will be evaluated.
Read the detailed description
The study consists of a screening period, a randomization period, a treatment period, a post-treatment safety follow-up followed by a long-term follow-up period.
JSB462 administration starts at day 1 of randomization, whereas AAA617 administration starts at day 1 of treatment period. Participants in arm 1 and arm 2 will therefore receive JSB462 during the 14-day randomization period before first administration of AAA617.
- JSB462 is administered orally, daily and continuously (100 mg or 300 mg once a day (QD)) until disease progression per Prostate Cancer Working Group (PCWG) 3-modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision.
- AAA617 will be administered at 7.4 gigabecquerel (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.
During the post-treatment follow up period:
- Safety follow-Up: After discontinuation of study treatment, all participants will be followed for at least 1 safety follow-up visit (30 days [+/- 7 days] after end of treatment visit). Subsequent lines of therapy may be administered according to investigator's discretion after treatment discontinuation.
- Long-term follow-up: Starts after the Safety follow-up period and lasts until the end of study. Safety, efficacy and survival information may be collected from the participants during this period.
- Conditions
- Prostatic Cancer, Castration-Resistant
- Being tested
- JSB462, AAA617
- Keywords
- Prostate cancer, metastatic Castration Resistant Prostate Cancer (mCRPC), Castration-resistant, Prostate-Specific Membrane Antigen (PSMA), PSMA-positive, Radioligand Therapy (RLT), lutetium (177Lu) vipivotide tetraxetan, Phase 2, Open-label, Androgen Receptor Pathway Inhibitor (ARPI)
- Medical subject headings
- Prostatic Neoplasms, Castration-Resistant, Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JSB462Drug
Also called luxdegalutamide
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
AAA617Drug
Also called Pluvicto, [177Lu]Lu-PSMA-617
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
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | JSB462 100 mg QD + AAA617 7.4 GBq Q6W Receives: Drug: JSB462; Drug: AAA617 |
| Arm 2 | Experimental | JSB462 300 mg QD + AAA617 7.4 GBq Q6W Receives: Drug: JSB462; Drug: AAA617 |
| Arm 3 | Active comparator | AAA617 7.4 GBq Q6W Receives: Drug: AAA617 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prostate Specific Antigen 50 (PSA50) Rate
Prostate Specific Antigen 50 (PSA50) Rate is defined as the proportion of participants who achieve a ≥50% decrease from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks without any PSA progression in between
Measured: From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Incidence rate of adverse events (AEs)
The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
Measured: From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Number of participants with dose adjustments
The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.
Measured: From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Duration of exposure to study treatment
Dose interruptions, dose reductions, drug discontinuations, dose intensity, and duration of exposure to study treatment (all study drugs).
Measured: From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Secondary outcomes (24)
Radiographic Progression Free Survival (rPFS)
Radiographic Progression Free Survival (rPFS) is defined as the time between randomization and the first occurrence of disease progression (per PCWG3-modified RECIST 1.1 as assessed by the investigator) or death due to any cause
Measured: 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
Overall Survival (OS)
Overall Survival (OS) is defined as the time between randomization and death due to any cause
Measured: From date of randomization until date of death from any cause, assessed up to approximately 41 months
Incidence rate of adverse events (AEs)
The analysis of adverse events and laboratory abnormalities will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
Measured: From date of randomization until date of death from any cause, assessed up to approximately 41 months
Overall Response Rate (ORR)
Overall Response Rate (ORR) is defined as the proportion of participants achieving a confirmed complete response (CR) or partial response (PR) per PCWG3-modified RECIST 1.1 as assessed by the investigator
Measured: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 41 months
Disease Control Rate (DCR)
Disease Control Rate (DCR) is defined as the proportion of participants achieving a CR, PR or stable disease (SD) per PCWG3-modified RECIST 1.1 as assessed by the investigator
Measured: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 41 months
Duration of Response (DOR)
Duration of Response (DOR) is defined as the time between first documented CR/PR and disease progression or death due to any cause per PCWG3-modified RECIST 1.1 as assessed by the investigator
Measured: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 41 months
Time to Response (TTR)
Time to response (TTR) is defined as the time from randomization to the date of first documented CR or PR per PCWG3-modified RECIST 1.1 as assessed by the investigator
Measured: From date of randomization until date of first documented Complete Response (CR) or Partial Response (PR), assessed up to approximately 41 months
Time to soft tissue progression (TTSTP)
Time to soft tissue progression (TTSTP) is defined as the time from randomization to the date of first documented radiographic soft tissue progression per PCWG3-modified RECIST 1.1 as assessed by the investigator
Measured: 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
Prostate Specific Antigen 90 (PSA90) Rate
Prostate Specific Antigen 90 (PSA90) Rate is defined as the proportion of participants who achieve a ≥90% decrease in PSA from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks without any PSA progression in between.
Measured: From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Prostate Specific Antigen 30 (PSA30) Rate
Prostate Specific Antigen 30 (PSA30) Rate is defined as the proportion of participants who achieve a ≥30% decrease from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks without any PSA progression in between
Measured: From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Prostate Specific Antigen 0 (PSA0) Rate
Prostate Specific Antigen 0 (PSA0) Rate is defined as the proportion of participants who achieve a PSA level <0.2 ng/ml at any timepoint after start of treatment, confirmed by a second PSA measurement ≥3 weeks without any PSA progression in between
Measured: From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Duration of biochemical response (DBR)
Duration of biochemical response (DBR) is defined as the time between the first date of PSA50 response and the date of PSA progression (an increase ≥25% in PSA and an absolute increase of ≥2 ng/mL above the NADIR confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, or a ≥25% increase and a ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline) or death due to any cause.
Measured: From date of date of first PSA50 response until date of PSA progression or death from any cause, assessed up to approximately 41 months
Time to first symptomatic skeletal event (TTSSE)
Time to first symptomatic skeletal event (TTSSE) is defined as the date of randomization to the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause, whichever occurs first
Measured: 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.
Plasma concentrations of JSB462 and plasma concentrations of its metabolite ARV-767
JSB462 pharmacokinetic (PK) samples will be obtained and evaluated in all participants at all dose levels in JSB462 treatment arms.
Measured: 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.
Concentrations of AAA617 in blood over time and PK parameters from blood radioactivity data
AAA617 pharmacokinetic (PK) samples will be obtained and evaluated in all participants at all dose levels in AAA617 treatment arm.
Measured: 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.
Area under the AAA617 concentration-time curve from time zero to the time of last quantifiable concentration (AUClast)
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.
Measured: 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.
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of AAA617
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUCinf will be listed and summarized using descriptive statistics.
Measured: 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.
Observed maximum blood concentration (Cmax) of AAA617
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
Measured: 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.
Time of maximum observed blood concentration occurrence (Tmax) of AAA617
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
Measured: 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.
Terminal elimination half-life (T1/2) of AAA617
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. The half-life will be listed and summarized using descriptive statistics.
Measured: 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.
Total systemic clearance for intravenous administration (CL) of AAA617
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.
Measured: 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.
Volume of distribution during the terminal phase following intravenous elimination (Vz) of AAA617
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.
Measured: 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.
Radiation absorbed doses in organs and tumors for AAA617
The organ absorbed radiation dose (Gy/GBq) as well as the effective radiation dose (mSv/GBq) will be evaluated and summarized descriptively.
Measured: 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.
Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
The PRO-CTCAE is a patient-reported outcomes measurement system developed by the National Cancer Institute as a companion to the CTCAE. It includes items covering participant-reported symptomatic adverse events (AEs) from the CTCAE. Each symptomatic AE concept has up to three items evaluating frequency, severity, or interference, focused on the study population and treatment regimens.
Participants respond on a 5-point scale for each item:
- Frequency: Never, Rarely, Occasionally, Frequently, Almost constantly
- Severity: None, Mild, Moderate, Severe, Very severe
- Interference: Not at all, A little bit, Somewhat, Quite a bit, Very much
The past 7-day recall version is used, focusing on relevant symptoms like fatigue, diarrhea, and hot flashes.
Measured: From date of randomization until date of death from any cause, assessed up to approximately 41 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2025
- Study start3 Jul 2025
- Primary completion16 Jul 2027 (estimated)
- Study completion14 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostatic Cancer, Castration-ResistantStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 138 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07047118
- Sponsor's protocol ID
- CJSB462B12201
- Other IDs
- 2024-520155-24-00
- Status last verified
- Oct 2026
- First submitted
- 20 May 2025
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT07047118
- Acronym / sponsor ID
- CJSB462B12201
- Conditions
- Prostatic Cancer, Castration-Resistant
- Keywords
- Prostate cancer, metastatic Castration Resistant Prostate Cancer (mCRPC), Castration-resistant, Prostate-Specific Membrane Antigen (PSMA), PSMA-positive, Radioligand Therapy (RLT), lutetium (177Lu) vipivotide tetraxetan, Phase 2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 138 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 3 Jul 2025 (actual)
- Primary completion
- 16 Jul 2027 (estimated)
- Study completion
- 14 May 2028 (estimated)
- First posted
- 2 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase II study aims to evaluate the efficacy and safety of the combination of JSB462 (also known as luxdegalutamide) at 100 mg and 300 mg QD doses + lutetium (177Lu) vipivotide tetraxetan (hereafter referred as AAA617) compared with AAA617 (control) in participants with metastatic Castration Resistant Prostate Cancer (mCRPC) with prior exposure to at least 1 Androgen Receptor Pathway Inhibitor (ARPI) and 0-2 taxane regimens and to select the recommended dose of the combination for phase III. Towards that end, the totality of the efficacy, safety, tolerability and pharmacokinetic (PK) data from participants randomized in the study will be evaluated.
Detailed description
The study consists of a screening period, a randomization period, a treatment period, a post-treatment safety follow-up followed by a long-term follow-up period.
JSB462 administration starts at day 1 of randomization, whereas AAA617 administration starts at day 1 of treatment period. Participants in arm 1 and arm 2 will therefore receive JSB462 during the 14-day randomization period before first administration of AAA617.
- JSB462 is administered orally, daily and continuously (100 mg or 300 mg once a day (QD)) until disease progression per Prostate Cancer Working Group (PCWG) 3-modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision.
- AAA617 will be administered at 7.4 gigabecquerel (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.
During the post-treatment follow up period:
- Safety follow-Up: After discontinuation of study treatment, all participants will be followed for at least 1 safety follow-up visit (30 days [+/- 7 days] after end of treatment visit). Subsequent lines of therapy may be administered according to investigator's discretion after treatment discontinuation.
- Long-term follow-up: Starts after the Safety follow-up period and lasts until the end of study. Safety, efficacy and survival information may be collected from the participants during this period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: JSB462, Drug: AAA617JSB462 100 mg QD + AAA617 7.4 GBq Q6W |
| Arm 2 | Experimental | Drug: JSB462, Drug: AAA617JSB462 300 mg QD + AAA617 7.4 GBq Q6W |
| Arm 3 | Active comparator | Drug: AAA617AAA617 7.4 GBq Q6W |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JSB462Also: luxdegalutamideAdministered 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 | Drug | Arm 1, Arm 2 |
| AAA617Also: Pluvicto, [177Lu]Lu-PSMA-617administered 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 | Drug | Arm 1, Arm 2, Arm 3 |
Primary outcome
Prostate Specific Antigen 50 (PSA50) Rate
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Prostate Specific Antigen 50 (PSA50) Rate is defined as the proportion of participants who achieve a ≥50% decrease from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks without any PSA progression in between
Incidence rate of adverse events (AEs)
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 30 months
The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
Number of participants with dose adjustments
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 30 months
The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.
Duration of exposure to study treatment
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Dose interruptions, dose reductions, drug discontinuations, dose intensity, and duration of exposure to study treatment (all study drugs).
24 secondary outcomes
Radiographic Progression Free Survival (rPFS)
Time frame: 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
Overall Survival (OS)
Time frame: From date of randomization until date of death from any cause, assessed up to approximately 41 months
Incidence rate of adverse events (AEs)
Time frame: From date of randomization until date of death from any cause, assessed up to approximately 41 months
Overall Response Rate (ORR)
Time frame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 41 months
Disease Control Rate (DCR)
Time frame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 41 months
Duration of Response (DOR)
Time frame: From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 41 months
Time to Response (TTR)
Time frame: From date of randomization until date of first documented Complete Response (CR) or Partial Response (PR), assessed up to approximately 41 months
Time to soft tissue progression (TTSTP)
Time frame: 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
Prostate Specific Antigen 90 (PSA90) Rate
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Prostate Specific Antigen 30 (PSA30) Rate
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Prostate Specific Antigen 0 (PSA0) Rate
Time frame: From date of randomization till 30 days safety fup, assessed up to approximately 30 months
Duration of biochemical response (DBR)
Time frame: From date of date of first PSA50 response until date of PSA progression or death from any cause, assessed up to approximately 41 months
Time to first symptomatic skeletal event (TTSSE)
Time frame: 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.
Plasma concentrations of JSB462 and plasma concentrations of its metabolite ARV-767
Time frame: 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.
Concentrations of AAA617 in blood over time and PK parameters from blood radioactivity data
Time frame: 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.
Area under the AAA617 concentration-time curve from time zero to the time of last quantifiable concentration (AUClast)
Time frame: 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.
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of AAA617
Time frame: 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.
Observed maximum blood concentration (Cmax) of AAA617
Time frame: 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.
Time of maximum observed blood concentration occurrence (Tmax) of AAA617
Time frame: 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.
Terminal elimination half-life (T1/2) of AAA617
Time frame: 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.
Total systemic clearance for intravenous administration (CL) of AAA617
Time frame: 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.
Volume of distribution during the terminal phase following intravenous elimination (Vz) of AAA617
Time frame: 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.
Radiation absorbed doses in organs and tumors for AAA617
Time frame: 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.
Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Time frame: From date of randomization until date of death from any cause, assessed up to approximately 41 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
44 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing JSB462 and AAA617 in people with Prostatic Cancer, Castration-Resistant, run by Novartis Pharmaceuticals at 44 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States, Israel, Spain, Australia, Austria and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prostate Specific Antigen 50 (PSA50) Rate (time frame: From date of randomization till 30 days safety fup, assessed up to approximately 30 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026.