An open-label study of JSB462 (luxdegalutamide) in combination with abiraterone in adult male patients with metastatic hormone-sensitive prostate cancer (mHSPC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Oct 2025 → ongoing

Decision date (initial)

2025-08-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2024-520156-22-00

WHO UTN

U1111-1321-8049

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

To determine the dose of JSB462 (100 mg QD vs 300 mg QD) in combination with abiraterone based on an integrated assessment of efficacy, safety and tolerability across study treatments
To compare JSB462 (100mg QD /300mg QD pooled doses or best of the two doses) in combination with abiraterone versus control (ARPI) in terms of efficacy, safety, and
tolerability.

Secondary objectives 9

1. To evaluate radiological progression-free survival (rPFS) across study treatments
2. To evaluate overall survival (OS) across study treatments
3. To evaluate the xxxx safety across study treatments
4. In participants with evaluable soft tissue disease by RECIST v1.1 at baseline: To evaluate the overall response rate (ORR), disease control rate (DCR), duration of response (DOR), time to response (TTR), and time to soft tissue progression (TTSTP) based on PCWG3-modified RECIST 1.1 (Eisenhauer et al 2009) as assessed by the investigator across study treatments
5. To evaluate biochemical response to investigational treatment(s) as measured by PSA across study treatments
6. To evaluate the durability of biochemical response across study treatments
7. To evaluate the time to first symptomatic skeletal event (TTSSE) across study treatments
8. To characterize the PK of JSB462 and its metabolite, ARV-767
9. To characterize patient-reported outcomes of interest to complement evidence of clinical safety and efficacy outcomes across study treatments

Conditions and MedDRA coding

Metastatic hormone-sensitive prostate cancer

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤2
2. Histologically confirmed adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible
3. 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
4. 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.

Exclusion criteria 2

1. 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 an 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
2. Participants with biochemical recurrence only or those without evidence of metastatic disease by radiological imaging (CT/MRI or bone scan) are not eligible

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. PSA90 rate 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.
2. Type, frequency and severity of AEs per CTCAE version 5.0 and changes in laboratory values, vital signs, and ECGs
3. Tolerability: dose interruptions, dose reductions, drug discontinuations, dose intensity, and duration of exposure to study treatment (all study drugs)

Secondary endpoints 15

1. rPFS defined as 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
2. OS defined as time between randomization and death due to any cause
3. Type, frequency and severity of xxxx AEs and changes in laboratory values (xxxx) as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0)
4. ORR defined as proportion of participants achieving a confirmed complete response (CR) or partial response (PR) per PCWG3-modified RECIST 1.1 as assessed by the investigator
5. DCR defined as proportion of participants achieving a CR, PR or stable disease (SD) per PCWG3-modified RECIST 1.1 as assessed by the investigator
6. DOR defined as time between first documented CR/PR and disease progression or death due to any cause per PCWG3-modified RECIST 1.1 as assessed by the investigator
7. TTR defined as the time from randomization to the date of first documented CR or PR per PCWG3-modified RECIST 1.1 as assessed by the investigator
8. TTSTP defined as time from randomization to the date of first documented radiographic soft tissue progression per PCWG3-modified RECIST 1.1 as assessed by the investigator
9. PSA30 rate defined as the proportion of participants who achieve a ≥30% decrease from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks without any PSA progression in between
10. PSA50 rate 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
11. PSA0, defined as the proportion of participants who achieve a PSA level <0.2 ng/ml at any timepoint after start of treatment, confirmed by a second PSA measurement ≥3 weeks without any PSA progression in between
12. Duration of biochemical response defined as time between PSA90 and/or PSA0 and PSA progression (increase ≥25% in PSA and an absolute increase of ≥2 ng/mL from NADIR) or death due to any cause
13. 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
14. Plasma concentrations of JSB462 and ARV-767 pre and post dose
15. Frequency, severity, and/or interference of selected items as assessed using the PRO-CTCAE

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Comparator 4

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 11

Locations

7 EU/EEA countries · 32 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 71 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications