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A Phase 3, Open-label, Multicenter, Randomized Study of Xaluritamig vs Cabazitaxel or Second Androgen Receptor-Directed Therapy in Subjects With Metastatic Castration-Resistant Prostate Cancer Previously Treated With Chemotherapy

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

Tagashira Shuzo

Amgen K.K.

Midtown Tower 9-7-1 Akasaka, Minato-ku, Tokyo

clinicaltrials_japan@amgen.com

Local Contact

Amgen K.K.

Midtown Tower 9-7-1 Akasaka, Minato-ku, Tokyo

+81-80-7217-8592

clinicaltrials_japan@amgen.com

Not Recruiting

Dec. 09, 2024

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1. Participant has provided informed consent prior to initiation of any study-specific activities/procedures.
2. Age >= 18 years (or >= 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. Mixed histologies (eg, adenocarcinoma with neuroendocrine component) are not permitted.
4. mCRPC with >= 1 metastatic lesion that is present on baseline computed tomography (CT), magnetic resonance imaging (MRI), or bone scan imaging obtained within 28 days prior to enrollment.
5. Evidence of progressive disease, defined as 1 or more PCWG3 criteria:
- Serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL.
- Soft-tissue progression defined as an increase >= 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions.
- Progression of bone disease: defined by the appearance of at least 2 new bone lesion(s) by bone scan (as per the 2+2 PCWG3 criteria).
6. Participants must have had a prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (< 50ng/dL or < 1.7 nmol/L).
7. Prior progression on at least one ARDT (enzalutamide, abiraterone, apalutamide, darolutamide).
8. Prior treatment with only one taxane therapy in the mCRPC setting. Note: Prior treatment with docetaxel in the metastatic hormone-sensitive prostate cancer (mHSPC) setting is permitted; however, participants must have also received one, and only one, taxane therapy in the mCRPC setting.
9. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
10. Adequate organ function.
11. Life expectancy of >= 12 weeks per the treating physician's assessment.

Prior & Concomitant Therapy:
1. Prior six transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted therapy.
2. Any anticancer therapy, immunotherapy, or investigational agent within 4 weeks prior to the first dose of study treatment, not including androgen receptor pathway inhibitors (ARPIs) (abiraterone, enzalutamide, darolutamide, apalutamide): minimum washout of 2 weeks prior to the first dose of study treatment and androgen suppression therapy (eg, luteinizing hormone-releasing hormone/gonadotropin-releasing hormone [LHRH/GnRH] analogue [agonist/antagonist]).
3. Prior Prostate-Specific Membrane Antigen (PSMA) radioligand therapy (RLT) within 3 months of the first dose of study treatment unless participants received < 2 cycles of therapy.
4. Prior palliative radiotherapy within 2 weeks of first dose of study treatment. Participants 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. Prior radionuclide therapy (Radium-223) within 2 months of first dose of study treatment.
7. Treatment with live and live-attenuated vaccines within 4 weeks before the first dose of study treatment.

Disease Related:
8. Participants with a history of central nervous system (CNS) metastasis. Note: Participants with treated, asymptomatic, and clinically stable dural metastases are eligible.
9. Unresolved toxicities from prior anti-tumor therapy not having resolved to CTCAE 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.

Male

Metastatic Castration-resistant Prostate Cancer

Experimental : Xaluritamig
- Participants with metastatic castration-resistant prostate cancer (mCRPC) will be randomized to receive Xaluritamig as an intravenous (IV)infusion.
- Interventions:
Drug: Xaluritamig

Active Comparator : Cabazitaxel/Abiraterone/Enzalutamide
- Participants with mCRPC will be randomized to receive cabazitaxel as an IV infusion, or a second androgen receptor-directed therapy of either abiraterone as oral tablets, or enzalutamide as oral tablets at the investigator's discretion.
- Interventions:
Drug: Abiraterone
Drug: Enzalutamide
Drug: Cabazitaxel

1. Overall Survival (OS) [Time Frame: Up to approximately 53 months]

1. Radiographic Progression-free Survival (rPFS) per Prostate Cancer Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Blinded Independent Central Review (BICR) [Time Frame: Up to approximately 53 months]
2. Objective Response Rate per Modified RECIST v1.1 as Assessed by BICR [Time Frame: Up to approximately 53 months]
3. Duration of Response (DOR) per Modified RECIST v1.1 as Assessed by BICR [Time Frame: Up to approximately 53 months]
4. Disease Control Rate per Modified RECIST v1.1 as Assessed by BICR [Time Frame: Up to approximately 53 months]

5. Time to Response (TTR) per Modified RECIST v1.1 as Assessed by BICR [Time Frame: Up to approximately 53 months]
6. Time to First Symptomatic Skeletal Events (SSE) [Time Frame: Up to approximately 53 months]
7. Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [Time Frame: Up to approximately 53 months]
8. Change from Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain Score [Time Frame: Baseline and approximately 53 months]
9. Change from Baseline in BPI-SF Pain Intensity Scale Score [Time Frame: Baseline and approximately 53 months]
10. Change from Baseline in BPI-SF Pain Interference Scale Score [Time Frame: Baseline and approximately 53 months]
11. Change from baseline in the European Quality of Life 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score [Time Frame: Baseline and approximately 53 months]
12. Change from baseline in the EQ-5D-5L Visual Analogue Scale (VAS) [Time Frame: Baseline and approximately 53 months]
13. Change from Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Total Score and Subscale Score [Time Frame: Baseline and approximately 53 months]
14. Time to Worsening in BPI-SF Worst Pain Score [Time Frame: Up to approximately 53 months]
15. Time to Worsening in BPI-SF Pain Intensity Scale Score [Time Frame: Up to approximately 53 months]
16. Time to Worsening in BPI-SF Pain Interference Scale Score [Time Frame: Up to approximately 53 months]
17. Time to Worsening in FACT-P Total Score [Time Frame: Up to approximately 53 months]
18. Time to Pain Improvement in Participants with Moderate/Severe Pain at Baseline [Time Frame: Up to approximately 53 months]
19. Time to Pain Improvement after Worsening in BPI-SF Pain Intensity Scale Score [Time Frame: Up to approximately 53 months]
20. Time to Pain Improvement after Worsening in BPI-SF Pain Interference Scale [Time Frame: Up to approximately 53 months]
21. Number of Patient-Reported Symptomatic AEs per Patient-reported Outcome - Common Terminology Criteria for Adverse Events (PRO-CTCAE) Item Library [Time Frame: Up to approximately 53 months]
22. Patient-Reported Summary Scores for Overall Bother of Side Effects per FACT-P [Time Frame: Up to approximately 53 months]
23. Percentage of Participants Achieving a => 50% Reduction in Prostate-specific Antigen (PSA) (PSA50) [Time Frame: Up to approximately 53 months]
24. Percentage of Participants Achieving a => 90% Reduction in PSA (PSA90) [Time Frame: Up to approximately 53 months]
25. Maximum Serum Concentration (Cmax) of Xaluritamig [Time Frame: Up to approximately 53 months]
26. Time to Cmax (Tmax) of Xaluritamig [Time Frame: Up to approximately 53 months]
27. Minimum Serum Concentration (Cmin) of Xaluritamig [Time Frame: Up to approximately 53 months]
28. Area Under the Concentration-time Curve (AUC) of Xaluritamig [Time Frame: Up to approximately 53 months]
29. Accumulation Following Multiple Dosing of Xaluritamig [Time Frame: Up to approximately 53 months]
30. Half-life (t1/2) of Xaluritamig [Time Frame: Up to approximately 53 months]
31. Number of Participants with Anti-xaluritamig Antibody [Time Frame: Up to approximately 53 months]

+81-11-811-9111

Jan. 09, 2025

Yes

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

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