Clinical trial • Phase II • Oncology
LUXDEGALUTAMIDE for Metastatic castration-resistant prostate cancer (mCRPC)
Phase II trial of LUXDEGALUTAMIDE for Metastatic castration-resistant prostate cancer (mCRPC).
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Metastatic castration-resistant prostate cancer (mCRPC)
- Trial Stage
- Phase II
- Drug Modality
- Small molecule | Radiopharmaceutical | Diagnostic agent
Key dates
- Initial CTIS Submission Date
- 06-06-2025
- First CTIS Authorization Date
- 17-09-2025
Trial design
Randomised, open-label, comparator: aaa617 (lutetium (177lu) vipivotide tetraxetan; pluvicto) alone. experimental arms: jsb462 (luxdegalutamide) 100 mg qd or 300 mg qd in combination with aaa617.-controlled Phase II trial in Netherlands, Austria, Germany and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Comparator: AAA617 (lutetium (177Lu) vipivotide tetraxetan; Pluvicto) alone. Experimental arms: JSB462 (luxdegalutamide) 100 mg QD or 300 mg QD in combination with AAA617.
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 41
- Trial Duration For Participant
- 1149
Eligibility
Recruits 41 No vulnerable populations selected. The trial enrols adult male participants only; informed consent is obtained from the adult participant. No assent process for minors is described..
- Vulnerable Population
- No vulnerable populations selected. The trial enrols adult male participants only; informed consent is obtained from the adult participant. No assent process for minors is described.
Inclusion criteria
- {"criterion_text":"- Adult male participants with histologically and/or cytologically confirmed adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible.\n- An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade ≤2.\n- 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.\n- Participants must be gallium (68Ga) gozetotide PET/CT scan positive and eligible as determined by the sponsor’s central reader.\n- Participant must have prior exposure to at least one second generation ARPI in the metastatic/advanced setting.\n- Previous treatment with a maximum of 2 taxane regimens is allowed.\n- 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)."}
Exclusion criteria
- {"criterion_text":"- Prior treatment with any RLT (approved or investigational) is not allowed\n- Prior treatment with a protein degrader compound that targets AR is not allowed"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Efficacy: PSA50 rate defined as the proportion of participants who achieve a ≥50% decrease in PSA from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks without any PSA progression in between","definition_or_measurement_approach":"PSA50 rate defined as proportion achieving ≥50% decrease in PSA from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks without PSA progression in between."}
- {"endpoint_text":"- Safety: Type, frequency and severity of AEs per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and changes in laboratory values, vital signs, and ECGs.","definition_or_measurement_approach":"Safety assessed by type, frequency and severity of AEs per CTCAE v5.0 and changes in labs, vital signs, and ECGs."}
- {"endpoint_text":"- Tolerability: Dose interruptions, dose reductions, drug discontinuations, dose intensity, and duration of exposure to study treatment (all study drugs).","definition_or_measurement_approach":"Tolerability assessed by tracking dose interruptions, dose reductions, drug discontinuations, dose intensity, and duration of exposure to study treatments."}
Secondary endpoints
- {"endpoint_text":"- rPFS defined as time between randomization and the first occurrence of disease progression (per PCWG3-modified RECIST v1.1 as assessed by the investigator) or death due to any cause","definition_or_measurement_approach":"rPFS = time from randomization to first disease progression per PCWG3-modified RECIST v1.1 (investigator assessment) or death from any cause."}
- {"endpoint_text":"- OS defined as time between randomization and death due to any cause","definition_or_measurement_approach":"OS = time from randomization to death from any cause."}
- {"endpoint_text":"- • Type, frequency and severity of AEs and SAEs • Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0) and timing","definition_or_measurement_approach":"Safety endpoints include type, frequency, severity of AEs/SAEs and laboratory abnormalities graded per NCI CTCAE v5.0 with timing."}
- {"endpoint_text":"- Endpoints assessed per PCWG3-modified RECIST v1.1 by investigator’s assessment: • ORR - proportion of participants with complete response (CR) or partial response (PR); • DCR - proportion of participants with CR, PR or stable disease (SD); • DOR - time from CR/PR to disease progression or death; • TTR - time from randomization to CR or PR; • TTSTP - time from randomization to soft tissue progression.","definition_or_measurement_approach":"ORR, DCR, DOR, TTR, TTSTP assessed per PCWG3-modified RECIST v1.1 by investigator."}
- {"endpoint_text":"- • PSA90 rate - proportion of participants with ≥90% decrease from baseline at any timepoint, confirmed by a second measurement ≥3 weeks; • PSA30 rate - proportion of participants with ≥30% decrease from baseline at any timepoint, confirmed by a second measurement ≥3 weeks; • PSA0 rate - proportion of participants with PSA <0.2 ng/ml at any timepoint, confirmed by a second measurement ≥3 weeks.","definition_or_measurement_approach":"PSA-based response rates (PSA90, PSA30, PSA0) defined as specified, each confirmed by a second measurement ≥3 weeks later."}
- {"endpoint_text":"- Duration of biochemical response defined as time between PSA50 and PSA progression or death due to any cause","definition_or_measurement_approach":"Duration measured from date of PSA50 to PSA progression or death from any cause."}
- {"endpoint_text":"- TTSSE defined as 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","definition_or_measurement_approach":"TTSSE measured from randomization to first of listed symptomatic skeletal events or death."}
- {"endpoint_text":"- Plasma concentrations of JSB462 and ARV-767 pre and post dose","definition_or_measurement_approach":"PK measurement of plasma concentrations of JSB462 and its metabolite ARV-767 pre- and post-dose."}
- {"endpoint_text":"- Concentrations of AAA617 in blood over time and PK parameters from blood radioactivity data","definition_or_measurement_approach":"PK of AAA617 evaluated from blood radioactivity data and concentration-time profiles."}
- {"endpoint_text":"- Radiation absorbed doses in organs and tumors for AAA617","definition_or_measurement_approach":"Dosimetry: radiation absorbed doses in organs and tumors measured for AAA617."}
- {"endpoint_text":"- Frequency, severity, and/or interference of selected items as assessed using the PRO-CTCAE","definition_or_measurement_approach":"Patient-reported symptom frequency, severity and interference measured using PRO-CTCAE instrument."}
Recruitment
- Planned Sample Size
- 41
- Recruitment Window Months
- 38
- Consent Approach
- Informed consent obtained from adult participants. Main informed consent forms and subject information sheets are provided (adult ICFs) and country-specific ICFs are available in multiple languages (English, German, French, Spanish, Dutch, Italian, Czech) as per submitted documents. Additional partner information and follow-up documents (e.g., for female partner and pregnant partner follow-up) are provided.
Methods
- Recruitment arrangements (K1 documents) submitted per country (document titles listed in CTIS document list).
- Advertisements (K2 documents) — advertisement materials listed for multiple countries (document titles present for Italy, Spain, Germany, Netherlands).
- Third-party supported recruitment: Jumo Health USA Inc. listed with duty 'Patient Recruitment and Retention Materials'; Scout Clinical listed with duty 'Patient Reimbursement'.
Geography
- Total Number Of Sites
- 22
- Total Number Of Participants
- 46
Netherlands
- Earliest CTIS Part Ii Submission Date
- 27-08-2025
- Latest Decision Or Authorization Date
- 26-01-2026
- Processing Time Days
- 152
- Number Of Sites
- 4
- Number Of Participants
- 6
Sites
- Site Name
- Frisius MC
- Department Name
- #2202; oncology
- Principal Investigator Name
- Bart Rikhof
- Principal Investigator Email
- bart.rikhof@frisiusmc.nl
- Contact Person Name
- Bart Rikhof
- Contact Person Email
- bart.rikhof@frisiusmc.nl
- Site Name
- Canisius Wilhelmina Ziekenhuis
- Department Name
- #2203; urology
- Principal Investigator Name
- Rik Somford
- Principal Investigator Email
- r.somford@cwz.nl
- Contact Person Name
- Rik Somford
- Contact Person Email
- r.somford@cwz.nl
- Site Name
- Spaarne Gasthuis Stichting
- Department Name
- #2200; oncology
- Principal Investigator Name
- Aart Beeker
- Principal Investigator Email
- abeeker@spaarnegasthuis.nl
- Contact Person Name
- Aart Beeker
- Contact Person Email
- abeeker@spaarnegasthuis.nl
- Site Name
- Maasstad Ziekenhuis Stichting
- Department Name
- #2201; oncology
- Principal Investigator Name
- Brigitte Haberkorn
- Principal Investigator Email
- haberkornb@maasstadziekenhuis.nl
- Contact Person Name
- Brigitte Haberkorn
- Contact Person Email
- haberkornb@maasstadziekenhuis.nl
Austria
- Earliest CTIS Part Ii Submission Date
- 04-09-2025
- Latest Decision Or Authorization Date
- 17-02-2026
- Processing Time Days
- 166
- Number Of Sites
- 3
- Number Of Participants
- 5
Sites
- Site Name
- Medical University Of Vienna
- Department Name
- 1200: Department of Urology
- Principal Investigator Name
- Gero Kramer
- Principal Investigator Email
- gero.kramer@meduniwien.ac.at
- Contact Person Name
- Gero Kramer
- Contact Person Email
- gero.kramer@meduniwien.ac.at
- Site Name
- Medizinische Universitaet Innsbruck
- Department Name
- 1202: Department of nuclear medicine
- Principal Investigator Name
- Isabel Maria Heidegger-Pircher
- Principal Investigator Email
- isabel.heidegger@tirol-kliniken.at
- Contact Person Name
- Isabel Maria Heidegger-Pircher
- Contact Person Email
- isabel.heidegger@tirol-kliniken.at
- Site Name
- Ordensklinikum Linz GmbH
- Department Name
- 1201: Department of Urology and Andrology
- Principal Investigator Name
- Ferdinand Luger
- Principal Investigator Email
- ferdinand.luger@ordensklinikum.at
- Contact Person Name
- Ferdinand Luger
- Contact Person Email
- ferdinand.luger@ordensklinikum.at
Germany
- Earliest CTIS Part Ii Submission Date
- 04-09-2025
- Latest Decision Or Authorization Date
- 02-01-2026
- Processing Time Days
- 120
- Number Of Sites
- 3
- Number Of Participants
- 8
Sites
- Site Name
- Universitaetsklinikum Essen AöR
- Department Name
- #1800: Klinik und Poliklinik für Urologie
- Principal Investigator Name
- Boris Hadaschik
- Principal Investigator Email
- Boris.hadaschik@uk-essen.de
- Contact Person Name
- Boris Hadaschik
- Contact Person Email
- Boris.hadaschik@uk-essen.de
- Site Name
- Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)
- Department Name
- #1802: Klinik und Poliklinik für Nuklearmedizin
- Principal Investigator Name
- Matthias Eiber
- Principal Investigator Email
- matthias.eiber@tum.de
- Contact Person Name
- Matthias Eiber
- Contact Person Email
- matthias.eiber@tum.de
- Site Name
- Rostock University Medical Center
- Department Name
- #1801: Klinik und Poliklinik für Urologie
- Principal Investigator Name
- Angelika Borkowetz
- Principal Investigator Email
- angelika.borkowetz@med.uni-rostock.de
- Contact Person Name
- Angelika Borkowetz
- Contact Person Email
- angelika.borkowetz@med.uni-rostock.de
Italy
- Earliest CTIS Part Ii Submission Date
- 31-07-2025
- Latest Decision Or Authorization Date
- 08-01-2026
- Processing Time Days
- 161
- Number Of Sites
- 2
- Number Of Participants
- 4
Sites
- Site Name
- IRCCS Ospedale Policlinico San Martino
- Department Name
- #2001, U.O. Oncologia Medica 1
- Principal Investigator Name
- Matteo Bauckneht
- Principal Investigator Email
- matteo.bauckneht@hsanmartino.it
- Contact Person Name
- Matteo Bauckneht
- Contact Person Email
- matteo.bauckneht@hsanmartino.it
- Site Name
- I.F.O. Istituti Fisioterapici Ospitalieri
- Department Name
- #2000; U.O.C. Oncologia Medica 1
- Principal Investigator Name
- Fabio Calabrò
- Principal Investigator Email
- fabio.calabro@ifo.it
- Contact Person Name
- Fabio Calabrò
- Contact Person Email
- fabio.calabro@ifo.it
France
- Earliest CTIS Part Ii Submission Date
- 18-09-2025
- Latest Decision Or Authorization Date
- 09-01-2026
- Processing Time Days
- 113
- Number Of Sites
- 3
- Number Of Participants
- 6
Sites
- Site Name
- Institut Paoli Calmettes
- Department Name
- #1700: Oncology
- Principal Investigator Name
- Gwenaelle GRAVIS
- Principal Investigator Email
- gravisg@ipc-unicancer.fr
- Contact Person Name
- Gwenaelle GRAVIS
- Contact Person Email
- gravisg@ipc-unicancer.fr
- Site Name
- Centre Hospitalier Regional Universitaire De Tours
- Department Name
- #1702: Oncology
- Principal Investigator Name
- Mathilde CANCEL
- Principal Investigator Email
- m.cancel@chu-tours.fr
- Contact Person Name
- Mathilde CANCEL
- Contact Person Email
- m.cancel@chu-tours.fr
- Site Name
- Centre Hospitalier Regional Et Universitaire De Brest
- Department Name
- #1701: Oncology
- Principal Investigator Name
- Benjamin AUBERGER
- Principal Investigator Email
- benjamin.auberger@chu-brest.fr
- Contact Person Name
- Benjamin AUBERGER
- Contact Person Email
- benjamin.auberger@chu-brest.fr
Czechia
- Earliest CTIS Part Ii Submission Date
- 27-08-2025
- Latest Decision Or Authorization Date
- 13-02-2026
- Processing Time Days
- 170
- Number Of Sites
- 2
- Number Of Participants
- 5
Sites
- Site Name
- Fakultni Nemocnice V Motole
- Department Name
- #1602, Onkologicka klinika
- Principal Investigator Name
- Tomas Buchler
- Principal Investigator Email
- tomas.buchler@lfmotol.cuni.cz
- Contact Person Name
- Tomas Buchler
- Contact Person Email
- tomas.buchler@lfmotol.cuni.cz
- Site Name
- University Hospital Olomouc
- Department Name
- #1601, Onkologicka klinika
- Principal Investigator Name
- Hana Studentova
- Principal Investigator Email
- hana.studentova@fnol.cz
- Contact Person Name
- Hana Studentova
- Contact Person Email
- hana.studentova@fnol.cz
Spain
- Earliest CTIS Part Ii Submission Date
- 26-08-2025
- Latest Decision Or Authorization Date
- 05-01-2026
- Processing Time Days
- 132
- Number Of Sites
- 5
- Number Of Participants
- 12
Sites
- Site Name
- University Hospital Virgen Del Rocio S.L.
- Department Name
- #2503, Oncologist
- Principal Investigator Name
- Begoña Perez Valderrama
- Principal Investigator Email
- mbegona.perez.sspa@juntadeandalucia.es
- Contact Person Name
- Begoña Perez Valderrama
- Contact Person Email
- mbegona.perez.sspa@juntadeandalucia.es
- Site Name
- University Clinical Hospital Virgen De La Arrixaca
- Department Name
- #2502, Oncologist
- Principal Investigator Name
- Silverio Ros Martínez
- Principal Investigator Email
- silverio.ros@carm.es
- Contact Person Name
- Silverio Ros Martínez
- Contact Person Email
- silverio.ros@carm.es
- Site Name
- Hospital Universitario Central De Asturias
- Department Name
- #2504, Oncologist
- Principal Investigator Name
- Carlos Álvarez Fernández
- Principal Investigator Email
- carlos.alvarezf@sespa.es
- Contact Person Name
- Carlos Álvarez Fernández
- Contact Person Email
- carlos.alvarezf@sespa.es
- Site Name
- Hospital Universitario Virgen De Las Nieves
- Department Name
- #2501, Oncologist
- Principal Investigator Name
- Raquel Luque Caro
- Principal Investigator Email
- rluquc@fundacionhvn.org
- Contact Person Name
- Raquel Luque Caro
- Contact Person Email
- rluquc@fundacionhvn.org
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- #2500; Oncologist
- Principal Investigator Name
- Joaquin Mateo Valderrama
- Principal Investigator Email
- jmateo@vhio.net
- Contact Person Name
- Joaquin Mateo Valderrama
- Contact Person Email
- jmateo@vhio.net
Sponsor
Primary sponsor
- Full Name
- Novartis Pharma AG
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Switzerland
Contract research organisations
- Name
- Icon Clinical Research Limited
- Responsibilities
- sponsorDuties codes: 1, 4
- Name
- Parexel International (IRL) Limited
- Responsibilities
- sponsorDuties codes: 12
- Name
- IQVIA Limited
- Responsibilities
- sponsorDuties codes: 3 (and other IQVIA entries with codes 1)
- Name
- Veeda Clinical Research Limited
- Responsibilities
- sponsorDuties codes: 4
- Name
- Syneos Health Inc.
- Responsibilities
- sponsorDuties codes: 1
Third parties
- {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties codes: 1, 4","organisation_type":"Pharmaceutical company"}
- {"country":"India","full_name":"Veeda Clinical Research Limited","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
- {"country":"Austria","full_name":"ABF Pharmaceutical Services GmbH","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}
- {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsorDuties codes: 12","organisation_type":"Pharmaceutical company"}
- {"country":"Netherlands","full_name":"GE Healthcare B.V. (Eindhoven)","duties_or_roles":"Radiolabelling of Locametz with radioactive gallium (68Ga)","organisation_type":"Pharmaceutical company"}
- {"country":"Austria","full_name":"Mag. Andreas Raffeiner GmbH","duties_or_roles":"sponsorDuties codes: 8","organisation_type":"Pharmaceutical company"}
- {"country":"Netherlands","full_name":"GE Healthcare B.V. (Zwolle)","duties_or_roles":"Radiolabelling of Locametz with radioactive gallium (68Ga)","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"IQVIA Limited (Reading)","duties_or_roles":"sponsorDuties codes: 3","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Imaging assessment","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Netherlands","full_name":"GE Healthcare B.V. (Simon Smitweg)","duties_or_roles":"Radiolabelling of Locametz with radioactive gallium (68Ga) Ga)","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"IQVIA Limited (alternate entry)","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United Kingdom","full_name":"IQVIA Limited (3 Forbury Place entry)","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"PRO management, PRO licensing, Formatting and Translations","organisation_type":"Pharmaceutical company"}
- {"country":"France","full_name":"Kayentis","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Jumo Health USA Inc.","duties_or_roles":"Patient Recruitment and Retention Materials","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 6, 7","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Pharmaceutical company"}
- {"country":"Ireland","full_name":"Icon Clinical Research (EU) - additional entry","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Luxdegalutamide
- Active Substance
- LUXDEGALUTAMIDE
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- Not authorised (prodAuthStatus 1)
- Starting Dose
- 100 mg
- Dose Levels
- 100 mg; 300 mg
- Frequency
- QD (once daily)
- Maximum Dose
- 300 mg (maxDailyDoseAmount 300 mg)
- Dose Escalation Increase
- 100 mg -> 300 mg
- Investigational Product Name
- Pluvicto 1 000 MBq/mL solution for injection/infusion
- Active Substance
- LUTETIUM (177LU) VIPIVOTIDE TETRAXETAN (AAA617)
- Modality
- Radiopharmaceutical
- Routes Of Administration
- INTRAVENOUS
- Route
- Intravenous
- Authorisation Status
- Authorised (marketing authorisation EU/1/22/1703/001)
- Starting Dose
- 7.4 GBq (maxDailyDoseAmount 7.4 GBq stated in product record)
- Dose Levels
- Not specified in protocol text; product record shows daily dose 7.4 GBq and max total dose amount 44.4 GBq
- Maximum Dose
- 7.4 GBq (per administration); max total dose amount 44.4 GBq
- Combination Treatment
- Yes
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