A Phase II, randomized, open-label, multi-center study of JSB462 (luxdegalutamide) in combination with lutetium (177Lu) vipivotide tetraxetan in adult male patients with PSMA-positive metastatic castration resistant prostate cancer (mCRPC)

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

16 Oct 2025 → ongoing

Decision date (initial)

2025-09-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Therapy

- To determine JSB462 dose for phase III (100 mg or 300 mg QD) in combination with AAA617 based on efficacy, safety and tolerability
- To compare JSB462 pooled doses or best of the two doses 100 mg /300 mg QD in combination with AAA617 versus AAA617 alone in terms of efficacy, safety and tolerability

Secondary objectives 11

1. To evaluate rPFS across study treatments
2. To evaluate OS across study treatments
3. To evaluate the renal 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 v1.1 assessed by the investigator across study treatments
5. To evaluate biochemical response 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 the PK of AAA617
10. To evaluate tumor and organs dosimetry of AAA617 across study treatments
11. To characterize patient-reported outcomes of interest to complement evidence of clinical safety and efficacy outcomes

Conditions and MedDRA coding

Metastatic castration resistant prostate cancer (mCRPC)

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 7

1. Adult male participants with histologically and/or cytologically confirmed adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible.
2. An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade ≤2.
3. 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.
4. Participants must be gallium (68Ga) gozetotide PET/CT scan positive and eligible as determined by the sponsor’s central reader.
5. Participant must have prior exposure to at least one second generation ARPI in the metastatic/advanced setting.
6. Previous treatment with a maximum of 2 taxane regimens is allowed.
7. 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 2

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Efficacy: PSA50 rate defined as the proportion of participants who achieve a ≥50% decrease in PSA from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks without any PSA progression in between
2. Safety: Type, frequency and severity of AEs per Common Terminology Criteria for Adverse Events (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 11

1. rPFS defined as time between randomization and the first occurrence of disease progression (per PCWG3-modified RECIST v1.1 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 AEs and SAEs • Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0) and timing
4. Endpoints assessed per PCWG3-modified RECIST v1.1 by investigator’s assessment: • ORR - proportion of participants with complete response (CR) or partial response (PR); • DCR - proportion of participants with CR, PR or stable disease (SD); • DOR - time from CR/PR to disease progression or death; • TTR - time from randomization to CR or PR; • TTSTP - time from randomization to soft tissue progression.
5. • PSA90 rate - proportion of participants with ≥90% decrease from baseline at any timepoint, confirmed by a second measurement ≥3 weeks; • PSA30 rate - proportion of participants with ≥30% decrease from baseline at any timepoint, confirmed by a second measurement ≥3 weeks; • PSA0 rate - proportion of participants with PSA <0.2 ng/ml at any timepoint, confirmed by a second measurement ≥3 weeks.
6. Duration of biochemical response defined as time between PSA50 and PSA progression or death due to any cause
7. 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
8. Plasma concentrations of JSB462 and ARV-767 pre and post dose
9. Concentrations of AAA617 in blood over time and PK parameters from blood radioactivity data
10. Radiation absorbed doses in organs and tumors for AAA617
11. Frequency, severity, and/or interference of selected items as assessed using the PRO-CTCAE

Investigational products

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

Test 2

Auxiliary 1

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 18

Locations

7 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 2 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

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

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