A Study of JSB462 (Luxdegalutamide) Plus Lutetium (177Lu) Vipivotide Tetraxetan in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)

NCT07047118 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CJSB462B122012024-520155-24-00
• Study Type: interventional
• Target: 138
• Locations: 14 countries
• Sites: 43

Brief 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 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.

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; Open-label; Androgen Receptor Pathway Inhibitor (ARPI)

Outcome Measures

Primary Outcomes (4)

• 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

  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.

  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.

  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).

  From date of randomization till 30 days safety fup, assessed up to approximately 30 months

Secondary Outcomes (24)

• Radiographic Progression Free Survival (rPFS)

  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)

  From date of randomization until date of death from any cause, assessed up to approximately 41 months

• Incidence rate of adverse events (AEs)

  From date of randomization until date of death from any cause, assessed up to approximately 41 months

• Overall Response Rate (ORR)

  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)

  From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 41 months

Study Arms (3)

Arm 1

EXPERIMENTAL

JSB462 100 mg QD + AAA617 7.4 GBq Q6W

Drug: JSB462; Drug: AAA617

Arm 2

EXPERIMENTAL

JSB462 300 mg QD + AAA617 7.4 GBq Q6W

Drug: JSB462; Drug: AAA617

Arm 3

ACTIVE COMPARATOR

AAA617 7.4 GBq Q6W

Drug: AAA617

Interventions

JSB462 DRUG

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

Also known as: luxdegalutamide

Arm 1; Arm 2

AAA617 DRUG

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

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

Arm 1; Arm 2; Arm 3

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• Prior treatment with any RLT (approved or investigational) is not allowed
• Prior treatment with a protein degrader compound that targets AR is not allowed

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (46)

City of Hope National Medical

Duarte, California, 91010, United States

Location

Providence Saint Johns Health Ctr

Santa Monica, California, 90404, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Yale University School Of Medicine

New Haven, Connecticut, 06520, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

XCancer Omaha LLC

Omaha, Nebraska, 68130, United States

Location

NYU Laura and Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Univ of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Texas Oncology Sammons Cancer Center

Dallas, Texas, 78246, United States

Location

Urology San Antonio

San Antonio, Texas, 78229, United States

Location

Novartis Investigative Site

Darlinghurst, New South Wales, 2010, Australia

Location

Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

Location

Novartis Investigative Site

Melbourne, Victoria, 3004, Australia

Location

Novartis Investigative Site

Innsbruck, Tyrol, 6020, Austria

Location

Novartis Investigative Site

Linz, 4020, Austria

Location

Novartis Investigative Site

Vienna, 1090, Austria

Location

Novartis Investigative Site

Burnaby, British Columbia, V5G 4P3, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3T 1E2, Canada

Location

Novartis Investigative Site

Beijing, 100034, China

Location

Novartis Investigative Site

Beijing, 100036, China

Location

Novartis Investigative Site

Olomouc, 779 00, Czechia

Location

Novartis Investigative Site

Prague, 150 06, Czechia

Location

Novartis Investigative Site

Brest, 29200, France

Location

Novartis Investigative Site

Marseille, 13273, France

Location

Novartis Investigative Site

Tours, 37044, France

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Rostock, 18057, Germany

Location

Novartis Investigative Site

Afula, 1834111, Israel

Location

Novartis Investigative Site

Beersheba, 8457108, Israel

Location

Novartis Investigative Site

Haifa, 3109601, Israel

Location

Novartis Investigative Site

Jerusalem, 9103102, Israel

Location

Novartis Investigative Site

Petah Tikva, 4941492, Israel

Location

Novartis Investigative Site

Ramat Gan, 5265601, Israel

Location

Novartis Investigative Site

Genova, GE, 16132, Italy

Location

Novartis Investigative Site

Roma, RM, 00128, Italy

Location

Novartis Investigative Site

Nijmegen, Gerlderland, 6532 SZ, Netherlands

Location

Novartis Investigative Site

Hoofddorp, 2134 TM, Netherlands

Location

Novartis Investigative Site

Singapore, 168583, Singapore

Location

Novartis Investigative Site

Seoul, 03722, South Korea

Location

Novartis Investigative Site

Seoul, 05505, South Korea

Location

Novartis Investigative Site

Granada, Andalusia, 18014, Spain

Location

Novartis Investigative Site

El Palmar, Murcia, 30120, Spain

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Seville, 41013, Spain

Location

Novartis Investigative Site

Taipei, 103616, Taiwan

Location

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant; Prostatic Neoplasms

Interventions

Pluvicto

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 20, 2025
• First Posted: July 2, 2025
• Study Start: July 3, 2025
• Primary Completion (Estimated): July 16, 2027
• Study Completion (Estimated): May 14, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

SG (1); CA (2); NL (2); US (11); IL (6); TW (1); CZ (2); AU (3); KR (2); DE (2); ES (4); CN (2); IT (2); FR (3)