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

NCT ID: NCT07047118

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

130 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-03

Study Completion Date

2028-11-04

Brief Summary

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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

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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

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Prostatic Cancer, Castration-Resistant

Keywords

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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)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1

JSB462 100 mg QD + AAA617 7.4 GBq Q6W

Group Type EXPERIMENTAL

JSB462

Intervention Type 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

AAA617

Intervention Type 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

Arm 2

JSB462 300 mg QD + AAA617 7.4 GBq Q6W

Group Type EXPERIMENTAL

JSB462

Intervention Type 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

AAA617

Intervention Type 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

Arm 3

AAA617 7.4 GBq Q6W

Group Type ACTIVE_COMPARATOR

AAA617

Intervention Type 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

Interventions

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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

Intervention Type DRUG

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 Type DRUG

Other Intervention Names

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luxdegalutamide Pluvicto [177Lu]Lu-PSMA-617

Eligibility Criteria

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Inclusion Criteria

* 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).

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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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XCancer Omaha LLC

Omaha, Nebraska, United States

Site Status RECRUITING

Univ of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Novartis Investigative Site

Darlinghurst, New South Wales, Australia

Site Status RECRUITING

Novartis Investigative Site

Adelaide, South Australia, Australia

Site Status RECRUITING

Novartis Investigative Site

Melbourne, Victoria, Australia

Site Status RECRUITING

Novartis Investigative Site

Vienna, , Austria

Site Status RECRUITING

Novartis Investigative Site

Marseille, , France

Site Status RECRUITING

Novartis Investigative Site

Essen, , Germany

Site Status RECRUITING

Novartis Investigative Site

Haifa, , Israel

Site Status RECRUITING

Novartis Investigative Site

Jerusalem, , Israel

Site Status RECRUITING

Novartis Investigative Site

Ramat Gan, , Israel

Site Status RECRUITING

Novartis Investigative Site

Singapore, , Singapore

Site Status RECRUITING

Novartis Investigative Site

Seoul, , South Korea

Site Status RECRUITING

Novartis Investigative Site

Seoul, , South Korea

Site Status RECRUITING

Novartis Investigative Site

Taipei, , Taiwan

Site Status RECRUITING

Countries

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United States Australia Austria France Germany Israel Singapore South Korea Taiwan

Central Contacts

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Novartis Pharmaceuticals

Role: CONTACT

Phone: 1-888-669-6682

Email: [email protected]

Novartis Pharmaceuticals

Role: CONTACT

Phone: +41613241111

Email: [email protected]

Facility Contacts

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Tony Romero

Role: primary

Faye Greiner

Role: primary

Other Identifiers

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2024-520155-24-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CJSB462B12201

Identifier Type: -

Identifier Source: org_study_id