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

JRCT ID: jRCT2011240073

Registered date:04/03/2025

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Metastatic Castration-resistant Prostate Cancer
• Date of first enrollment: 09/12/2024
• Target sample size: 675
• Countries of recruitment: United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

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

Outcome(s)

• Primary Outcome: 1. Overall Survival (OS) [Time Frame: Up to approximately 43 months]

Secondary Outcome

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 43 months]
2. Objective Response Rate per RECIST v1.1 as Assessed by BICR [Time Frame: Up to approximately 43 months]
3. Duration of Response (DOR) per RECIST v1.1 as Assessed by BICR [Time Frame: Up to approximately 43 months]
4. Disease Control Rate [Time Frame: Up to approximately 43 months]
5. Progression-free Survival (PFS) [Time Frame: Up to approximately 43 months]
6. Time to Response (TTR) per RECIST v1.1 as Assessed by BICR [Time Frame: Up to approximately 43 months]
7. Time to First Symptomatic Skeletal Events (SSE) [Time Frame: Up to approximately 43 months]
8. Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [Time Frame: Up to approximately 43 months]
9. Change from Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain Score [Time Frame: Baseline and approximately 43 months]
10. Change from Baseline in BPI-SF Pain Intensity Scale Score [Time Frame: Baseline and approximately 43 months]
11. Change from Baseline in BPI-SF Pain Interference Scale Score [Time Frame: Baseline and approximately 43 months]
12. Change from baseline in the European Quality of Life 5 Domain 5 Level Scale (EQ-5D-5L) Visual Analogue Scale (VAS) [Time Frame: Baseline and approximately 43 months]
13. Change from Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Total Score [Time Frame: Baseline and approximately 43months]
14. Time to Worsening in BPI-SF Worst Pain Score [Time Frame: Up to approximately 43 months]
15. Time to Worsening in BPI-SF Pain Intensity Scale Score [Time Frame: Up to approximately 43 months]
16. Time to Worsening in BPI-SF Pain Interference Scale Score [Time Frame: Up to approximately 43 months]
17. Time to Worsening in FACT-P Total Score [Time Frame: Up to approximately 43 months]
18. Time to Pain Improvement in Participants with Moderate/Severe Pain at Baseline [Time Frame: Up to approximately 43 months]
19. Time to Pain Improvement after Worsening in BPI-SF Pain Intensity Scale Score [Time Frame: Up to approximately 43 months]
20. Time to Pain Improvement after Worsening in BPI-SF Pain Interference Scale [Time Frame: Up to approximately 43 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 43 months]
22. Patient-Reported Summary Scores for Overall Bother of Side Effects per FACT-P [Time Frame: Up to approximately 43 months]
23. Percentage of Participants Achieving a => 50% Reduction in Prostate-specific Antigen (PSA) (PSA50) [Time Frame: Up to approximately 43 months]
24. Percentage of Participants Achieving a => 90% Reduction in PSA (PSA90) [Time Frame: Up to approximately 43 months]
25. Maximum Serum Concentration (Cmax) of Xaluritamig [Time Frame: Up to approximately 43 months]
26. Time to Cmax (Tmax) of Xaluritamig [Time Frame: Up to approximately 43 months]
27. Minimum Serum Concentration (Cmin) of Xaluritamig [Time Frame: Up to approximately 43 months]
28. Area Under the Concentration-time Curve (AUC) of Xaluritamig [Time Frame: Up to approximately 43 months]
29. Accumulation Following Multiple Dosing of Xaluritamig [Time Frame: Up to approximately 43 months]
30. Half-life (t1/2) of Xaluritamig [Time Frame: Up to approximately 43 months]
31. Number of Participants with Anti-xaluritamig Antibody [Time Frame: Up to approximately 43 months]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Male

Include criteria

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.
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 fornon-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions.
- Progression of bone disease: evaluable disease or new bone lesion(s) by bone scan (2+2 PCWG3 criteria, Scher et al, 2016).
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 treatment with at least one ARDT.
8. Prior treatment with one taxane therapy. Prior treatment with docetaxel in the hormone-sensitive setting is permitted. Participants who received two or more prior chemotherapy regimens in the castrate-resistant setting are not eligible.
9. Prior treatment with radioligand therapy (RLT), radionuclide therapy (Radium-223), poly ADP-ribose polymerase (PARP) inhibitor, or immune checkpoint inhibitor is permitted.
10. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
11. Adequate organ function.

Exclude criteria

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 suppression therapy.
3. Prior Prostate-Specific Membrane Antigen (PSMA) radioligand therapy (RLT) within 2 months of the first dose of study treatment unless participants received < 2 cycles of therapy. Participants who received 1 cycle of PSMA RLT within 35 days prior to the first dose of study treatment are also excluded.
4. Participants who started a bisphosphonate or denosumab regimen within 4 weeks prior to the first dose of study treatment.
5. Radiation therapy within 4 weeks prior to the first dose of study treatment (or local or focal radiotherapy within 2 weeks prior to the first dose of study treatment).
6. Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy, or investigational therapy.

Disease Related:
7. Participants with a history of central nervous system (CNS) metastasis.
8. Unresolved toxicities from prior anti-tumor therapy with 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.

Related Information

• Primary Sponsor: Tagashira Shuzo
• Secondary ID(s): NCT06691984