Phase 3 Study of Xaluritamig Plus Abiraterone vs Investigator's Choice in Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Nov 2025 → ongoing

Decision date (initial)

2025-11-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Amgen Inc.

External identifiers

EU CT number

2025-520555-89-00

WHO UTN

U1111-1324-1794

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Pharmacokinetic, Efficacy

To compare overall survival (OS) in participants receiving xaluritamig plus abiraterone against investigator's choice (docetaxel, cabazitaxel, or abiraterone)

Secondary objectives 9

1. To compare radiographic progression-free survival (rPFS) in participants receiving xaluritamig plus abiraterone against investigator's choice (docetaxel, cabazitaxel, or abiraterone)
2. To compare other measures of efficacy of xaluritamig plus abiraterone against investigator's choice (docetaxel, cabazitaxel, or abiraterone)
3. To compare symptomatic skeletal events (SSE) in participants treated with xaluritamig plus abiraterone against investigator's choice (docetaxel, cabazitaxel, or abiraterone)
4. To evaluate the safety and tolerability of xaluritamig plus abiraterone and investigator's choice (docetaxel, cabazitaxel, or abiraterone)
5. To evaluate health-related quality of life (HRQoL) of xaluritamig plus abiraterone and investigator's choice (docetaxel, cabazitaxel, or abiraterone)
6. To evaluate patient-reported safety and tolerability of xaluritamig plus abiraterone and investigator's choice (docetaxel, cabazitaxel, or abiraterone)
7. To evaluate the biochemical response of xaluritamig plus abiraterone and investigator's choice (docetaxel, cabazitaxel, or abiraterone)
8. To characterize the pharmacokinetics (PK) of xaluritamig plus abiraterone using intensive and sparse PK sampling
9. To evaluate the immunogenicity of xaluritamig plus abiraterone

Conditions and MedDRA coding

Metastatic castration-resistant prostate cancer (mCRPC)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

De-identified individual participant data for variables necessary to address the specific research question in an approved data sharing request.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participant has provided informed consent before initiation of any study-specific activities/procedures
2. Age greater than or equal to 18 years (or greater than or equal to legal age within the country if it is older than 18 years) at the time of signing the informed consent
3. Participant must have histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate
4. mCRPC with greater than or equal to 1 metastatic lesion that is present on baseline computed tomography (CT), magnetic resonance imaging (MRI), or bone scan imaging obtained within 28 days before enrollment
5. Evidence of progressive disease (PD), defined as 1 or more PCWG3-modified RECIST 1.1 criteria
6. Participants must have had prior orchiectomy and/or ongoing androgren-deprivation therapy (ADT) and a castrate level of serum testosterone (less than 50 ng/dL or less than 1.7 nmol/L)
7. Prior disease progression on 1, and only 1, androgen receptor pathway inhibitor (ARPI) (either enzalutamide, apalutamide, or darolutamide) is required
8. Participants intended to receive cabazitaxel must have previously received less than or equal to 6 cycles of docetaxel in the mHSPC setting
9. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
10. Adequate organ function

Exclusion criteria 12

1. Participants with a history of central nervous system (CNS) metastases
2. Concurrent cytotoxic chemotherapy, ARPI, immunotherapy, RLT, poly adenosine diphosphate ribose polymerase (PARP) inhibitor, biological therapy, investigational therapy
3. Treatment with live and live-attenuated vaccines within 4 weeks before the first dose of study treatment
4. Unresolved toxicities from prior antitumor therapy not having resolved to CTCAE version 5.0 grade 1 or baseline, with the exception of alopecia or toxicities that are stable and well-controlled AND there is an agreement to allow inclusion by both the investigator and the sponsor
5. Prior six transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted therapy
6. Prior disease progression on or intolerance to abiraterone
7. Prior treatment with any chemotherapy regimen in the mCRPC setting and/or greater than 6 cycles of docetaxel treatment in the mHSPC setting
8. Any anticancer therapy, immunotherapy, or investigational agent within 4 weeks before first dose of study treatment with the following exceptions:  Androgen receptor pathway inhibitors (ARPIs; enzalutamide, darolutamide, apalutamide): minimum washout of 2 weeks prior to the first dose of study treatment Androgen suppression therapy (eg, luteinizing hormone-releasing hormone/gonadotropin releasing hormone [LHRH/GnRH] analogue [agonist/antagonist]) is permitted.
9. Prior radioligand therapy (RLT) within 8 weeks of first dose of study treatment
10. Prior radionuclide therapy (radium-223) within 2 months of first dose of study treatment
11. Prior palliative radiotherapy within 2 weeks before first dose of study treatment. Participants must have recovered from all radiation-related toxicities
12. Prior CD3-directed therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS)

Secondary endpoints 21

1. rPFS per Prostate Cancer Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), per investigator assessment
2. Objective response per modified RECIST 1.1, per investigator assessment
3. Duration of Response (DOR) per modified RECIST 1.1, per investigator assessment
4. Disease Control per modified RECIST 1.1, per investigator assessment
5. Progression-free survival (PFS) 2, per investigator assessment
6. Time to Response (TTR), per modified RECIST 1.1, per investigator assessment
7. Time to first subsequent therapy
8. Time to symptomatic skeletal events (SSE)
9. Treatment-emergent adverse events, treatment-emergent serious adverse events, and fatal adverse events
10. Time to worsening as measured by: - BPI-SF Worst pain score - BPI-SF Pain intensity scale - BPI-SF Pain interference scale - FACT-P Total score
11. Time to improvement as measured by BPI-SF Worst pain score in participants with moderate/severe pain at baseline
12. Time to improvement after worsening as measured by BPI-SF Pain intensity scale score and BPI-SF Pain interference scale score
13. Patient-reported outcomes summary scores over time at each assessment as measured by: - Selected questions on symptomatic adverse events from the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) item library - The GP5 question on overall bother of side effects from the FACT-P questionnaire
14. Prostate-specific antigen (PSA) 50 and PSA 90 responses
15. Time to PSA 50 and PSA 90 responses
16. Duration of PSA 50 and PSA 90 response
17. Time to PSA progression
18. PK parameters for xaluritamig such as maximum serum concentration (Cmax), time to maximum concentration (Tmax), minimum serum concentration (Cmin), area under the concentration-time curve (AUC) over the dosing interval, accumulation following multiple dosing, and, if feasible, half-life (t1/2)
19. Abiraterone PK concentrations at end of dosing interval
20. Incidence of anti-xaluritamig antibody formation
21. Change from baseline over time at each assessment as measured by: - BPI-SF Worst pain score - BPI-SF Pain intensity scale - BPI-SF Pain interference scale - FACT-P Total score and subscale scores - EQ-5D-5L Utility score - Change from baseline in the EQ-5D-5L Visual Analogue Scale (VAS)

Investigational products

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

Test 4

Comparator 4

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1730

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 14

Locations

9 EU/EEA countries · 74 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 125 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