Study Evaluating the Safety, Tolerability, and Efficacy of Xaluritamig in Combination With Androgen Receptor Pathway Inhibitors in Participants With Metastatic Hormone-sensitive Prostate Cancer

Official title

A Phase 1b Open-label, Multicenter Study Evaluating the Safety, Tolerability, and Efficacy of Xaluritamig in Combination With Androgen Receptor Pathway Inhibitors in Participants With Metastatic Hormone-sensitive Prostate Cancer

Overview

The main objective of the trial is to evaluate the safety and tolerability of xaluritamig in combination with darolutamide or abiraterone.

Interventions

• Drug Xaluritamig
  Participants will receive xaluritamig intravenously.
• Drug Darolutamide
  Participants will receive darolutamide orally.
• Drug Abiraterone
  Participants will receive abiraterone orally.

Primary outcome measures

• Number of Participants with Treatment-emergent Adverse Events [Time frame: Up to approximately 2.5 years]
• Number of Participants with Treatment-related Adverse Events [Time frame: Up to approximately 2.5 years]
• Number of Participants with Clinically Significant Changes in Vital Signs [Time frame: Up to approximately 2.5 years]
• Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests [Time frame: Up to approximately 2.5 years]

Secondary outcome measures (10)

• Percentage of Participants with Prostate-specific Antigen (PSA) < 0.2 ng/mL at 6 Months [Time frame: 6 months]
• Time to PSA Progression [Time frame: Up to approximately 4.5 years]
• Time to First New Systemic Anticancer Therapy [Time frame: Up to approximately 4.5 years]
• Time to Radiographic Progression per Prostate Cancer Working Group 3 (PCWG3) Modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [Time frame: Up to approximately 4.5 years]
• Observed Concentration at the End of a Dose Interval of Darolutamide [Time frame: Up to approximately 4.5 years]
• Observed Concentration at the End of a Dose Interval of Abiraterone [Time frame: Up to approximately 4.5 years]
• Maximum Observed Serum Concentration (Cmax) of Xaluritmag [Time frame: Up to approximately 4.5 years]
• Time to Cmax (Tmax) of Xaluritmag [Time frame: Up to approximately 4.5 years]
• Area Under the Concentration Time Curve (AUC) of Xaluritmag [Time frame: Up to approximately 4.5 years]
• Half-life (t1/2) of Xaluritamig [Time frame: Up to approximately 4.5 years]

Eligibility criteria

Inclusion criteria

• Participants must have histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate. Mixed histologies (eg, adenocarcinoma with neuroendocrine component) are not permitted.
• Participants must have at the time of diagnosis:

• De novo (synchronous) mHSPC, defined as metastatic disease with no prior diagnosis of localized prostate cancer, AND started ADT (LHRH agonist/antagonist or orchiectomy) with or without ARPI (defined as abiraterone OR darolutamide) as SOC, first treatment with ADT should be no longer than 12 weeks before screening. Prior docetaxel treatment is not permitted.
• Participants must have at the time of diagnosis:

• High-volume metastatic disease defined as presence of visceral metastasis or metastases, and/or ≥ 4 bone metastases with at least one outside of the vertebral column and pelvis.
• Documented metastatic disease either by a positive bone scan, or for soft tissue or visceral metastases, either by contrast enhanced abdominal/pelvic/chest computed tomography (CT) or magnetic resonance imaging (MRI) scan.
• No documented PSA progression following the initial PSA nadir after starting ADT.

Exclusion criteria

• Prior history of central nervous system (CNS) metastases. Note: Participants with asymptomatic and clinically stable dural metastases are eligible.
• Unresolved toxicities from prior anti-tumor therapy (excluding those related to ongoing ADT and ARPI) not having resolved to Common Terminology Criteria for Adverse events (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.
• Autoimmune disease requiring systemic immunosuppression within the past 2 years.
• Participant with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active or systemic infection within 7 days prior to the first dose of study treatment.
• Prior six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted therapy.
• Prior radioligand therapy (RLT), poly-adenosine diphosphate ribose polymerase (PARP) inhibitor, cytotoxic chemotherapy, aminoglutethimide or ketoconazole for prostate cancer, or any prior systemic biologic therapy, including immunotherapy for prostate cancer.
• Prior enzalutamide or apalutamide within 15 days prior to enrolment.
• Requirement for chronic systemic corticosteroid therapy (prednisone dose greater than 10 mg per day or local equivalent) or any other immunosuppressive therapies (including anti TNFα therapies) unless stopped (with adequate tapering) within 7 days prior to dosing.
• Prior radiotherapy to all metastatic sites of disease. Radiotherapy to some sites of metastatic disease for palliation will be permitted.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 8 centers

• University of California San Francisco — San Francisco
• Dana Farber Cancer Institute — Boston
• University of Minnesota — Minneapolis
• Cleveland Clinic Foundation — Cleveland
• Thomas Jefferson University — Philadelphia
• University of Pittsburgh Medical Center Hillman Cancer Center — Pittsburgh
• South Texas Accelerated Research Therapeutics - Carolinas — Myrtle Beach
• Sarah Cannon Research Institute — Nashville

Australia · 5 centers

• Chris OBrien Lifehouse — Camperdown
• Calvary Mater Newcastle Hospital — Waratah
• Cabrini Hospital — Clayton
• Peter MacCallum Cancer Centre — Melbourne
• The Alfred Hospital — Melbourne

Switzerland · 3 centers

• Kantonsspital Graubuenden — Chur
• Centre Hospitalier Universitaire Vaudois — Lausanne
• Kantonsspital Sankt Gallen — Sankt Gallen

Identifiers

NCT: NCT07140900 · 20240361

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗