Clinical trial NCT06691984: Phase 3 Study of Xaluritamig vs Cabazitaxel or Second Androgen Receptor-Directed Therapy in Participants With Progressive Metastatic Castration-Resistant Prostate Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Castration-resistant Prostate Cancer
Keywords: Oncology
Xaluritamig
Cabazitaxel
Prostate cancer
Abiraterone
Enzalutamide
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2024-11-18
Enrollment: 675
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 \[ARDT\]).


Eligibility criteria: 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.
* 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.
  * Progression of bone disease: evaluable disease or new bone lesion(s) by bone scan (2+2 PCWG3 criteria, Scher et al, 2016).
* 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 treatment with at least one ARDT.
* 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.
* Prior treatment with radioligand therapy (RLT), radionuclide therapy (Radium-223), poly ADP-ribose polymerase (PARP) inhibitor, or immune checkpoint inhibitor is permitted.
* Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
* Adequate organ function.

Key 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 suppression therapy.
* 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.
* Participants who started a bisphosphonate or denosumab regimen within 4 weeks prior to the first dose of study treatment.
* 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).
* Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy, or investigational therapy.

Disease Related:

* Participants with a history of central nervous system (CNS) metastasis.
* 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 43 months
Secondary outcomes:
measure: 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)
timeFrame: Up to approximately 43 months
measure: Objective Response Rate per RECIST v1.1 as Assessed by BICR
timeFrame: Up to approximately 43 months
measure: Duration of Response (DOR) per RECIST v1.1 as Assessed by BICR
timeFrame: Up to approximately 43 months
measure: Disease Control Rate
timeFrame: Up to approximately 43 months
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 43 months
measure: Time to Response (TTR) per RECIST v1.1 as Assessed by BICR
timeFrame: Up to approximately 43 months
measure: Time to First Symptomatic Skeletal Events (SSE)
timeFrame: Up to approximately 43 months
measure: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 43 months
measure: Change from Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain Score
timeFrame: Baseline and approximately 43 months
measure: Change from Baseline in BPI-SF Pain Intensity Scale Score
timeFrame: Baseline and approximately 43 months
measure: Change from Baseline in BPI-SF Pain Interference Scale Score
timeFrame: Baseline and approximately 43 months
measure: Change from baseline in the European Quality of Life 5 Domain 5 Level Scale (EQ-5D-5L) Visual Analogue Scale (VAS)
timeFrame: Baseline and approximately 43 months
measure: Change from Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Total Score
timeFrame: Baseline and approximately 43 months
measure: Time to Worsening in BPI-SF Worst Pain Score
timeFrame: Up to approximately 43 months
measure: Time to Worsening in BPI-SF Pain Intensity Scale Score
timeFrame: Up to approximately 43 months
measure: Time to Worsening in BPI-SF Pain Interference Scale Score
timeFrame: Up to approximately 43 months
measure: Time to Worsening in FACT-P Total Score
timeFrame: Up to approximately 43 months
measure: Time to Pain Improvement in Participants with Moderate/Severe Pain at Baseline
timeFrame: Up to approximately 43 months
measure: Time to Pain Improvement after Worsening in BPI-SF Pain Intensity Scale Score
timeFrame: Up to approximately 43 months
measure: Time to Pain Improvement after Worsening in BPI-SF Pain Interference Scale
timeFrame: Up to approximately 43 months
measure: Number of Patient-Reported Symptomatic AEs per Patient-reported Outcome - Common Terminology Criteria for Adverse Events (PRO-CTCAE) Item Library
timeFrame: Up to approximately 43 months
measure: Patient-Reported Summary Scores for Overall Bother of Side Effects per FACT-P
timeFrame: Up to approximately 43 months
measure: Percentage of Participants Achieving a ≥50% Reduction in Prostate-specific Antigen (PSA) (PSA50)
timeFrame: Up to approximately 43 months
measure: Percentage of Participants Achieving a ≥90% Reduction in PSA (PSA90)
timeFrame: Up to approximately 43 months
measure: Maximum Serum Concentration (Cmax) of Xaluritamig
timeFrame: Up to approximately 43 months
measure: Time to Cmax (Tmax) of Xaluritamig
timeFrame: Up to approximately 43 months
measure: Minimum Serum Concentration (Cmin) of Xaluritamig
timeFrame: Up to approximately 43 months
measure: Area Under the Concentration-time Curve (AUC) of Xaluritamig
timeFrame: Up to approximately 43 months
measure: Accumulation Following Multiple Dosing of Xaluritamig
timeFrame: Up to approximately 43 months
measure: Half-life (t1/2) of Xaluritamig
timeFrame: Up to approximately 43 months
measure: Number of Participants with Anti-xaluritamig Antibody
timeFrame: Up to approximately 43 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Fullerton
country: United States
facility: Providence Saint Jude Medical Center
state: California
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Oncology Clinic and Pharmacy
state: South Dakota
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
city: Camperdown
country: Australia
facility: Chris OBrien Lifehouse
state: New South Wales
city: North Ryde
country: Australia
facility: Macquarie University
state: New South Wales
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Warrnambool
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Salzburg
country: Austria
facility: Landeskrankenhaus Salzburg
city: Sankt Poelten
country: Austria
facility: Universitaetsklinikum Sankt Poelten
city: Wien
country: Austria
facility: Krankenhaus der Barmherzigen Brueder Wien
city: Bruxelles
country: Belgium
facility: Universite Catholique de Louvain Cliniques Universitaires Saint Luc
city: Kortrijk
country: Belgium
facility: Algemeen Ziekenhuis Groeninge - Campus Kennedylaan
city: Vancouver
country: Canada
facility: BC Cancer Vancouver
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Sir Mortimer B Davis - Jewish General Hospital
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital
city: Vejle
country: Denmark
facility: Vejle Sygehus
city: Le Mans
country: France
facility: Clinique Victor Hugo - Centre Jean Bernard
city: Dresden
country: Germany
facility: Universitaetsklinikum Dresden
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der TUM
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: Athens
country: Greece
facility: Athens Medical Center S.A - Iatriko Amarousiou
city: Thessaloniki
country: Greece
facility: European Interbalkan Medical Center
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital, The University of Hong Kong
city: Foggia
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia
city: Gallipoli
country: Italy
facility: Ospedale Sacro Cuore di Gesù Azienda Sanitaria Locale di Lecce
city: Nagoya-shi
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Matsuyama-shi
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Sapporo-shi
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
state: Hokkaido
city: Yokohama-shi
country: Japan
facility: Yokohama City University Medical Center
state: Kanagawa
city: Osaka-shi
country: Japan
facility: Osaka International Cancer Institute
state: Osaka
city: Suita-shi
country: Japan
facility: The University of Osaka Hospital
state: Osaka
city: Bunkyo-ku
country: Japan
facility: Nippon Medical School Hospital
state: Tokyo
city: Koto-ku
country: Japan
facility: The Cancer institute Hospital of Japanese Foundation for Cancer Research
state: Tokyo
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Goyang-si, Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Seongnam-si, Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
city: Krakow
country: Poland
facility: SPZOZ Szpital Uniwersytecki w Krakowie
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
state: Cataluña
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset
city: Umea
country: Sweden
facility: Norrlands Universitetssjukhus
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Sankt Gallen
country: Switzerland
facility: Kantonsspital Sankt Gallen
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Izmir
country: Turkey
facility: Izmir Medical Point Hastanesi
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Guys Hospital
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: