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An Open-label Study of JSB462 (Luxdegalutamide) in Combination With Abiraterone in Adult Male Patients With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)

ConditionMetastatic Hormone-sensitive Prostate Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexMale
Age18+
SponsorNovartis Pharmaceuticals

About this trial

This Phase II study aims to evaluate efficacy and safety of the combination of JSB462 (also known as luxdegalutamide) at 100 mg and 300 mg once a day (QD) doses + abiraterone compared with an androgen receptor pathway inhibitor (ARPI, abiraterone or enzalutamide) in participants with metastatic Hormone Sensitive Prostate Cancer (mHSPC) and to select the recommended dose of the combination for phase III. Towards that end, the totality of the efficacy, safety, tolerability and PK data from participants randomized in the study will be evaluated

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • JSB462

    Drug

    JSB462 is administered orally, daily and continuously (100 mg or 300 mg QD) until disease progression per PCWG3-modified RECIST 1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision.

  • Abiraterone

    Drug

    Abiraterone 1000 mg is administered orally, daily and continuously until disease progression per PCWG3-modified RECIST 1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision.

  • Enzalutamide

    Drug

    Enzalutamide 160 mg is administered orally, daily and continuously until disease progression per PCWG3-modified RECIST 1.1 as assessed by the investigator, the occurrence of unacceptable toxicities, death, participant decision or investigator decision.

Treatment groups

150 Participants
are divided into 3 treatment groups
Group A: Arm 1Experimental treatment 2 interventions
Group B: Arm 2Experimental treatment 2 interventions
Group C: Arm 3Active comparator 2 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
From date of randomization till 30 days safety fup, assessed up to approximately 75 months
2

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.

Time frame
From date of randomization till 30 days safety fup, assessed up to approximately 75 months
3

Number of participants with dose adjustments

The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.

Time frame
From date of randomization till 30 days safety fup, assessed up to approximately 75 months
4

Duration of exposure to study treatment

The duration of exposure in weeks to study treatment and for each study treatment component (JSB462, abiraterone and enzalutamide) will be summarized for each study treatment component by means of descriptive statistics using the SAS.

Time frame
From date of randomization till 30 days safety fup, assessed up to approximately 75 months

Secondary outcomes

1

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

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 83 months
2

Overall Survival (OS)

Overall Survival (OS) is defined as the time between randomization and death due to any cause

Time frame
From date of randomization until date of death from any cause, assessed up to approximately 83 months
3

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.

Time frame
From date of randomization till 30 days safety fup, assessed up to approximately 83 months
4

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

Time frame
From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 83 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Novartis Pharmaceuticals

Lead sponsor

Source ClinicalTrials.gov
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