Phase 3 Study of Xaluritamig vs Cabazitaxel or Second Androgen Receptor-Directed Therapy in Subjects With Progressive Metastatic Castration-Resistant Prostate Cancer (XALute)

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

28 Apr 2025 → ongoing

Decision date (initial)

2025-04-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Amgen Inc.

External identifiers

EU CT number

2024-513968-25-00

WHO UTN

U1111-1313-0500

ClinicalTrials.gov

NCT06691984

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Pharmacokinetic, Safety

To compare overall survival (OS) in subjects receiving xaluritamig vs investigator’s choice (cabazitaxel or second androgen receptor-directed therapy [ARDT])

Secondary objectives 9

1. To compare radiographic progression-free survival (rPFS) in subjects receiving xaluritamig vs investigator’s choice (cabazitaxel or second ARDT)
2. To evaluate other measures of efficacy of xaluritamig vs investigator’s choice (cabazitaxel or second ARDT)
3. To compare symptomatic skeletal events (SSE) in subjects treated with xaluritamig vs investigator’s choice (cabazitaxel or second ARDT)
4. To evaluate the safety and tolerability of xaluritamig vs investigator’s choice (cabazitaxel or second ARDT)
5. To evaluate health-related quality of life (HRQoL) of xaluritamig vs investigator’s choice (cabazitaxel or second ARDT)
6. To evaluate patient-reported safety and tolerability of xaluritamig vs investigator’s choice (cabazitaxel or second ARDT)
7. Evaluate the biochemical response of xaluritamig vs investigator’s choice (cabazitaxel or second ARDT)
8. Characterize the pharmacokinetics (PK) of xaluritamig using intensive and sparse PK sampling
9. Evaluate the immunogenicity of xaluritamig

Conditions and MedDRA coding

Metastatic castration-resistant prostate cancer (mCRPC)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

De-identified individual patient 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. Subject has provided informed consent(s) prior to initiation of any study specific activities/procedures.
2. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
3. Adequate organ function
4. Age equal or greater than 18 years (or equal or greater than legal age within the country if it is older than 18 years) at the time of signing the informed consent
5. Subject must have histological, pathological and/or cytological confirmation of adenocarcinoma of the prostate. Mixed histologies (eg,adenocarcinoma with neuroendocrine component) are not permitted.
6. mCRPC with equal or greater than 1 metastatic lesion that is present on baseline computed tomography, magnetic resonance imaging, or bone scan imaging obtained within 28 days prior to enrollment.
7. Evidence of progressive disease, defined as 1 or more PCWG3 criteria
8. Subjects must have prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (less than 50 ng/dL or ;ess than 1.7 nmol/L). This must be assessed locally for eligibility
9. Prior progresion on at least one ARDT (enzalutamide, abiraterone, apalutamide, darolutamide)
10. Prior treatment with only one taxane therapy in mCRPC setting. Note: Prior treatment with docetaxel in the mHSPC setting is permitted; however, subjects must have also received one, and only one, taxane therapy in the mCRPC setting.

Exclusion criteria 7

1. Prior STEAP1-targeted therapy
2. Any anticancer therapy, immunotherapy, or investigational agent within 4 weeks prior to first dose of study treatment, with the following exceptions: - Androgen receptor pathway inhibitors (ARPIs; abiraterone, 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, or antagonist) is permitted.
3. Prior PSMA RLT within 2 months of first dose of study treatment unless subjects received less than 2 cycles of therapy. Subjects who received 1 cycle of PSMA RLT within 35 days prior to first dose of study treatment are also excluded.
4. Prior pallative radiotherapy within 2 weeks of first dose of study treatment. Subject must have recovered from all radiation-related toxicities.
5. Concurrent cytotoxic chemotherapy, ARDT, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy, investigational therapy. Note: Prior treatment with a PARP inhibitor is permitted as long as not within 4 weeks before first dose of study treatment.
6. Patients with a history of central nervous system (CNS) metastasis. Note: Subjects with treated, asymptomatic, and clinically stable dural metastases are eligible.
7. Unresolved toxicities from prior anti-tumor therapy with Common Terminology Criteria for Adverse Events version 5.0 events grade above 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival

Secondary endpoints 15

1. Radiographic progression-free survival per Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1, as assessed by blinded independent central review (BICR)
2. Objective response per modified RECIST v1.1, as assessed by BICR
3. Duration of response (DOR) per RECIST v1.1, as assessed by BICR
4. Disease control per modified RECIST v 1.1 as assessed by BICR
5. Time to Response (TTR) per modified RECIST v1.1, as assessed by BICR
6. Time to first symptomatic skeletal events
7. Treatment Emergent Adverse Events, Treatment Emergent Serious Adverse Events, and fatal adverse events
8. Change from baseline in: - Brief Pain Inventory - Short Form Worst pain score - BPI-SF Pain intensity scale - BPI-SF Pain interference scale - Functional Assessment of Cancer Therapy – Prostate Total score and subscale scores - European Quality of Life - 5 Domain 5 Level Scale Utility score - Change from baseline in the EQ-5D-5L Visual Analogue Scale
9. Time to worsening in: - Brief Pain Inventory - Short Form Worst pain score - Brief Pain Inventory - Short Form Pain intensity scale - Brief Pain Inventory - Short Form Pain interference scale - Functional Assessment of Cancer Therapy – Prostate Total score
10. Time to pain improvement in: - Subjects with moderate/severe pain at baseline
11. Time to improvement after worsening in: - Brief Pain Inventory - Short Form Pain intensity scale - Brief Pain Inventory - Short Form Pain interference scale
12. Patient-reported outcomes summary scores as assessed by: -Selected question on symptomatic adverse events from the Patient-Reported Outcomes version of the Common Terminology Criteria Adverse Events (PRO-CTCAE) item library -The GP5 question on overall bother of side effects from the Functional Assessment of Cancer Therapy – Prostate questionnaire
13. PSA50 and PSA90 responses
14. 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
15. Incidence of anti-xaluritamig antibody formation

Investigational products

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

Test 3

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

11 EU/EEA countries · 84 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 188 files

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

Application history

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