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

Purpose

The main objective of the study is to compare overall survival in participants receiving xaluritamig versus investigator's choice (cabazitaxel or second androgen receptor-directed therapy [ARDT]).

Condition

  • Metastatic Castration-resistant Prostate Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
Male
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Participant has provided informed consent prior to initiation of any study-specific activities/procedures. - Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years) at the time of signing the informed consent. - Participant must have histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate. Mixed histologies (eg, adenocarcinoma with neuroendocrine component) are not permitted. - 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. - 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). - Participants must have had a prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (< 50 ng/dL or < 1.7 nmol/L). - Prior progression on at least one ARDT (enzalutamide, abiraterone, apalutamide, darolutamide). - 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. - Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. - Adequate organ function. - Life expectancy of ≥ 12 weeks per the treating physician's assessment.

Exclusion Criteria

Prior & Concomitant Therapy: - Prior six transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted therapy. - 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]). - 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. - Prior palliative radiotherapy within 2 weeks of first dose of study treatment. Participants must have recovered from all radiation-related toxicities. - 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. - Prior radionuclide therapy (Radium-223) within 2 months of first dose of study treatment. - Treatment with live and live-attenuated vaccines within 4 weeks before the first dose of study treatment. Disease Related: - Participants with a history of central nervous system (CNS) metastasis. Note: Participants with treated, asymptomatic, and clinically stable dural metastases are eligible. - 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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Xaluritamig
Participants with metastatic castration-resistant prostate cancer (mCRPC) will be randomized to receive Xaluritamig as an intravenous (IV) infusion.
  • Drug: Xaluritamig
    Short-term IV infusion
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.
  • Drug: Abiraterone
    Oral tablets
  • Drug: Enzalutamide
    Oral tablets
  • Drug: Cabazitaxel
    IV infusion

Recruiting Locations

University of Alabama at Birmingham
Birmingham 4049979, Alabama 4829764 35233

City of Hope National Medical Center
Duarte 5344147, California 5332921 91010

Providence Saint Jude Medical Center
Fullerton 5351247, California 5332921 92835

Cedars Sinai Medical Center
Los Angeles 5368361, California 5332921 90048

University of California Irvine
Orange 5379513, California 5332921 92868

University of California San Francisco
San Francisco 5391959, California 5332921 94158

University of Florida, College of Medicine
Gainesville 4156404, Florida 4155751 32610

Sylvester Comprehensive Cancer Center-Fox Building
Miami 4164138, Florida 4155751 33136

AdventHealth Orlando
Orlando 4167147, Florida 4155751 32804

University of Chicago
Chicago 4887398, Illinois 4896861 60637

Indiana University
Indianapolis 4259418, Indiana 4921868 46202

University of Louisville Health - James Graham Brown Cancer Center
Louisville 4299276, Kentucky 6254925 40202

Norton Cancer Institute
Louisville 4299276, Kentucky 6254925 40207

Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926 02114

Beth Israel Deaconess Medical Center
Boston 4930956, Massachusetts 6254926 02215

Dana-Farber Cancer Institute
Boston 4930956, Massachusetts 6254926 02215

Henry Ford Hospital, Henry Ford Health Systems
Detroit 4990729, Michigan 5001836 48202

University of Minnesota
Minneapolis 5037649, Minnesota 5037779 55455

Washington University
St Louis 4407066, Missouri 4398678 63110

Yale New Haven Hospital
New York 5128581, New York 5128638 10032

Memorial Sloan Kettering Cancer Center
New York 5128581, New York 5128638 10065

Montefiore Medical Center
The Bronx 5110266, New York 5128638 10467

Levine Cancer Institute
Charlotte 4460243, North Carolina 4482348 28204

Duke University
Durham 4464368, North Carolina 4482348 27710

Sanford Roger Maris Cancer Center
Fargo 5059163, North Dakota 5690763 58122

Cleveland Clinic Foundation
Cleveland 5150529, Ohio 5165418 44195

The Ohio State University
Columbus 4509177, Ohio 5165418 43210

Oregon Health and Science University
Portland 5746545, Oregon 5744337 97239

Thomas Jefferson University Hospital
Philadelphia 4560349, Pennsylvania 6254927 19107

Fox Chase Cancer Center
Philadelphia 4560349, Pennsylvania 6254927 19111

University of Pittsburgh Medical Center
Pittsburgh 5206379, Pennsylvania 6254927 15232

Sanford Oncology Clinic and Pharmacy
Sioux Falls 5231851, South Dakota 5769223 57104

Sarah Cannon Research Institute
Nashville 4644585, Tennessee 4662168 37203

Tennessee Oncology PLLC
Nashville 4644585, Tennessee 4662168 37203

University of Texas Southwestern Medical Center
Dallas 4684888, Texas 4736286 75390

University of Texas MD Anderson Cancer Center
Houston 4699066, Texas 4736286 77030

Intermountain Medical Center
Murray 5778755, Utah 5549030 84107

Virginia Oncology Associates
Norfolk 4776222, Virginia 6254928 23502

Fred Hutchinson Cancer Center
Seattle 5809844, Washington 5815135 98019-1024

Swedish Medical Center
Seattle 5809844, Washington 5815135 98104

University of Wisconsin Carbone Cancer Center
Madison 5261457, Wisconsin 5279468 53705

Medical College of Wisconsin
Milwaukee 5263045, Wisconsin 5279468 53226

More Details

Status
Recruiting
Sponsor
Amgen

Study Contact

Amgen Call Center
866-572-6436
medinfo@amgen.com