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Luxdegalutamide (JSB462) plus abiraterone for high-volume metastatic hormone-sensitive prostate cancer

A Phase II, Randomized, Open-label, Multi-center Study of JSB462 (Luxdegalutamide) in Combination With Abiraterone in Adult Male Patients With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)

Phase 2 Interventional Novartis · NCT06991556

This study tests whether adding JSB462 (luxdegalutamide) at 100 mg or 300 mg once daily to abiraterone (or enzalutamide) helps men with high-volume metastatic hormone-sensitive prostate cancer keep their disease controlled longer with acceptable side effects.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment150 (estimated)
Ages18 Years and up
SexMale
SponsorNovartis Industry-sponsored
Drugs / interventionschemotherapy
Locations65 sites (La Jolla, California and 64 other locations)
Trial IDNCT06991556 on ClinicalTrials.gov

What this trial studies

This is a Phase II, open-label, randomized study comparing two doses of JSB462 (100 mg or 300 mg QD) given with abiraterone versus an androgen receptor pathway inhibitor (abiraterone or enzalutamide) in men with high-volume mHSPC. Study treatment is given orally and continued until disease progression, unacceptable toxicity, death, participant decision, or investigator decision. Participants undergo a 28-day screening period, a treatment period, a 30-day post-treatment safety follow-up, and a long-term follow-up for survival and safety data. Efficacy, safety, tolerability, and pharmacokinetic data will be used to select the recommended combination dose for phase III.

Who should consider this trial

Good fit: Men with histologically confirmed high-volume metastatic hormone-sensitive prostate adenocarcinoma, ECOG performance status ≤2, castrate testosterone levels, and no prior exposure to second-generation androgen receptor pathway inhibitors are ideal candidates.

Not a fit: Patients with mixed neuroendocrine histology, low-volume disease, poor performance status (ECOG >2), or prior treatment with second-generation AR pathway inhibitors are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could improve disease control and potentially extend progression-free and overall survival for men with high-volume mHSPC while maintaining acceptable safety.

How similar studies have performed: Other androgen-receptor pathway inhibitors have shown benefit in mHSPC, but combining luxdegalutamide with abiraterone is a novel combination approach being tested in this Phase II study.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

* An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤2
* Histologically confirmed adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible
* High-volume mHSPC, defined by the presence of ≥1 metastatic visceral non-nodal lesion and/or ≥4 metastatic bone lesions (with at least one lesion outside the vertebral column and/or pelvis) in imaging exams (CT/MRI or bone scan) according to local radiology assessment by the investigator obtained ≤28 days prior to randomization
* Participants must have a castrate level of serum/plasma testosterone (\<50 ng/dL or \<1.7 nmol/L). Ongoing ADT (as defined by prior orchiectomy and/or ongoing GnRH analog/antagonist) for ≤90 days is allowed prior to randomization, provided that PSA zero (PSA level \<0.2 ng/ml according to local laboratory as assessed by the investigator) is not achieved prior to randomization.

Key Exclusion Criteria:

* Prior exposure to a second generation ARPI (such as enzalutamide/darolutamide/apalutamide and/or abiraterone) for the treatment of advanced/metastatic disease is not allowed. Prior exposure to ARPI, to taxane chemotherapy (up to 6 cycles) or to RLT in the context of (neo)adjuvant treatment for localized prostate cancer is allowed, if the last dose of this treatment was administered \>12 months from randomization. Prior use of a first generation ARPI (such as bicalutamide) in the context of ADT initiation with a GnRH analog is allowed, provided the first generation ARPI was administered for ≤14 days and last dose was administered ≥7 days from randomization.
* Participants with biochemical recurrence only or those without evidence of metastatic disease by radiological imaging (CT/MRI or bone scan) are not eligible

Other inclusion/exclusion criteria may apply.

Where this trial is running

La Jolla, California and 64 other locations

+15 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Hormone-sensitive Prostate CancerInterventionalclinical trialopen-labelJSB462luxdegalutamideefficacysafety
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.