Clinical trial NCT06629779: A Study to Learn How PF-06821497 (Mevrometostat) Works in Men With Metastatic Castration-resistant Prostate Cancer.
Official title: A PHASE 3, RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED STUDY OF PF-06821497 (MEVROMETOSTAT) WITH ENZALUTAMIDE IN METASTATIC CASTRATION RESISTANT PROSTATE CANCER (MEVPRO-2)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Castration-Resistant Prostate Cancer
Keywords: MEVROMETOSTAT
METASTATIC CASTRATION RESISTANT PROSTATE CANCER
PF-06821497
EZH2
enhancer of zeste homologue-2
enzalutamide
mCRPC
Prostrate Cancer
castrate resistant prostate cancer
prostatecancer-study.com
efficacy
safety
pharmacokinetics
pharmacodynamics
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2024-10-08
Enrollment: 900
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: This study will explore whether a combination of the investigational drug PF-06821497 and enzalutamide will work better than taking enzalutamide alone in participants with mCRPC who are ARSi or abiraterone naïve.

Detailed description: This is a global, multicenter, randomized Phase 3 study evaluating PF-06821497 (mevrometostat) in combination with enzalutamide versus placebo in combination with enzalutamide in participants with mCRPC where no systemic anti-cancer treatments have been initiated after documentation of mCRPC with the exception of ADT (androgen deprivation therapy) and first-generation anti-androgen agents. Prior treatment with any of the ARSi's enzalutamide, darolutamide, apalutamide, or abiraterone acetate, is not permitted in any setting. Chemotherapy is permitted in the castrate sensitive setting.

This study consists of a Screening Phase, Randomization, Treatment Phase, Safety Follow-up, and Long-Term Follow-up. Participants will be randomized on a 1:1 basis to receive (Arm A) PF-06821497 in combination with enzalutamide, or (Arm B) placebo in combination with enzalutamide.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features.
* Metastatic disease in bone documented on bone scan, or in soft tissue documented on CT/MRI scan.
* Progressive disease in the setting of medical or surgical castration.
* ECOG performance status 0 or 1, with a life expectancy of ≥12 months as assessed by the investigator.

Exclusion Criteria:

* Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that make the participant inappropriate for the study.
* Known history of active inflammatory gastrointestinal disease, chronic diarrhea, or previous gastric resection or lap-band surgery.
* Clinically significant cardiovascular disease.
* Known or suspected brain metastasis or active leptomeningeal disease or clinically significant history of seizure.
* Any history of myelodysplastic syndrome, acute myeloid leukemia, or any other prior malignancy with a few exceptions.
* Participants must be treatment naïve at the mCRPC stage, eg, no cytotoxic chemotherapy, radio-ligand therapy (i.e. 177Lu- PSMA-617), CDK4/6 inhibitors, 5-alpha reductase inhibitors for prostate cancer in any setting, androgen receptor signaling inhibitors (ARSi) including enzalutamide, apalutamide, darolutamide, poly ADP-ribose polymerase (PARP) monotherapy or other systemic anti-cancer treatment with the following exceptions:

  1. Treatment with first-generation antiandrogen (ADT) agents;
  2. Docetaxel treatment is allowed for mCSPC, as long as no signs of failure, or disease progression occurred during treatment or within 3 months of treatment completion.
* Previous administration with an investigational product (drug or vaccine) within 30 days or 5 half-lives preceding the first dose of study intervention (whichever is longer).
* Inadequate organ function.

Primary outcomes:
measure: Radiographic Progression Free Survival (rPFS)
timeFrame: Randomization up to approximately 3 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Randomization up to approximately 5 years
measure: To demonstrate that PF-06821497 in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging TTPP
timeFrame: Randomization up to approximately 3 years
measure: Duration of Response (DoR) in measurable soft tissue disease
timeFrame: Randomization up to approximately 3 years.
measure: Time to prostate specific antigen (PSA) progression.
timeFrame: Randomization up to approximately 3 years
measure: Prostate Specific Antigen Response
timeFrame: Randomization up to approximately 3 years.
measure: Time to initiation of antineoplastic therapy.
timeFrame: Randomization up to approximately 3 years.
measure: Time to initiation of cytotoxic chemotherapy.
timeFrame: Randomization up to approximately 3 years
measure: Time to first symptomatic skeletal event
timeFrame: Randomization up to approximately 3 years.
measure: Progression free survival on next line of therapy
timeFrame: Randomization up to approximately 3 years
measure: Incidence of Adverse Events
timeFrame: Randomization up to approximately 5 years
measure: To assess circulating tumor DNA (ctDNA) at baseline and on treatment to evaluate tumor burden.
timeFrame: Baseline up to approximately 3 years.
measure: To evaluate the PK of PF-06821497 when dosed with enzalutamide
timeFrame: Cycle 1 Day 15 to last PK draw at Cycle 6 Day 1 (cycle length is 28 days)
measure: Change from baseline in patient reported pain symptoms per Brief Pain Inventory-Short Form (BPI-SF)
timeFrame: Randomization up to approximately 5 years
measure: Change from baseline in BPI-SF Item 3 (Worst Pain) at Cycle 7 Day 1 (Week 25)
timeFrame: Randomization up to Week 25
measure: Change from baseline in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy - Prostate (FACT-P)
timeFrame: Randomization up to approximately 5 years
measure: Change from baseline in patient reported health status per European Quality of Life 5-Dimension 5 Level (EQ-5D-5L)
timeFrame: Randomization up to approximately 5 years
measure: Symptomatic toxicity as measured by items from the Patient-Reported Outcome CTCAE (PRO-CTCAE)
timeFrame: Randomization up to approximately 5 years
measure: Time to definitive deterioration in patient-reported health related quality of life (HRQoL) per FACT-P
timeFrame: Randomization up to approximately 5 years
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Gilbert
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Glendale
country: United States
facility: Palo Verde Hematology Oncology
state: Arizona
city: Glendale
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Mesa
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Mesa
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Phoenix
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Scottsdale
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Tucson
country: United States
facility: Arizona Urology Specialists (East Side Location)
state: Arizona
city: Tucson
country: United States
facility: Arizona Urology Specialists (AUS)-Orange Grove
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology
state: Arkansas
city: Rogers
country: United States
facility: Highlands Oncology
state: Arkansas
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Hidden Valley Lake
country: United States
facility: Adventist Health Physicians Network
state: California
city: Napa
country: United States
facility: Adventist Health Physicians Network
state: California
city: Saint Helena
country: United States
facility: Adventist Health St. Helena
state: California
city: Lisle
country: United States
facility: Duly Health and Care (Bone Scintigraphy)
state: Illinois
city: Lisle
country: United States
facility: NextStage Clinical Research-Chicago-(04)
state: Illinois
city: Quincy
country: United States
facility: Blessing Hospital
state: Illinois
city: Quincy
country: United States
facility: Blessing Physician Services
state: Illinois
city: Westmont
country: United States
facility: Duly Health and Care (CT and MRI)
state: Illinois
city: Omaha
country: United States
facility: Adult & Pediatric Urology, PC
state: Nebraska
city: Bronx
country: United States
facility: Montefiore Medical Center - Medical Park
state: New York
city: Salisbury
country: United States
facility: Salisbury VA Medical Center
state: North Carolina
city: Myrtle Beach
country: United States
facility: AUC Urologists, LLC
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center, LLC
state: South Carolina
city: Myrtle Beach
country: United States
facility: Grand Strand Medical Center
state: South Carolina
city: Myrtle Beach
country: United States
facility: Parkway Surgery Center
state: South Carolina
city: San Antonio
country: United States
facility: USA Clinical Trials
state: Texas
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center - Montlake
state: Washington
city: Caba
country: Argentina
facility: Centro de Urología (CDU)
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Hospital Sirio Libanes
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Imagenes Mdq
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clínicas Mar del Plata
state: Buenos Aires
city: Capital
country: Argentina
facility: Centro Medico Privado CEMAIC
state: Córdoba
city: Cordoba
country: Argentina
facility: Hospital Privado Universitario de Córdoba
state: Córdoba
city: Buenos Aires
country: Argentina
facility: IMAXE
city: Buenos Aires
country: Argentina
facility: Asociación de Beneficencia Hospital Sirio Libanés
city: Buenos Aires
country: Argentina
facility: Centro Medico Fleischer
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra o Câncer
state: RIO Grande DO Norte
city: Santo André
country: Brazil
facility: CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
state: SÃO Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
state: SÃO Paulo
city: São José do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
state: SÃO Paulo
city: São Paulo
country: Brazil
facility: IBCC - Núcleo de Pesquisa e Ensino
city: Gabrovo
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Dr. Tota Venkova AD
city: Pleven
country: Bulgaria
facility: "University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski" EAD
city: Plovdiv
country: Bulgaria
facility: Complex Oncology Center - Plovdiv EOOD
city: Stara Zagora
country: Bulgaria
facility: Complex Oncology Center Stara Zagora EOOD
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Halifax
country: Canada
facility: QEII Health Sciences Centre - Victoria General Site
state: Nova Scotia
city: Oshawa
country: Canada
facility: Lakeridge Health
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
city: Wuhu
country: China
facility: Wannan Medical College Yijishan Hospital
state: Anhui
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Science
state: Beijing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Shantou
country: China
facility: The Second Affiliated Hospital of Shantou University School of Medicine
state: Guangdong
city: Guilin
country: China
facility: The Second Affiliated Hospital of Guilin Medical University
state: Guangxi
city: Xinxiang
country: China
facility: The Third Affiliated Hospital of Xinxiang Medical University
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Hohhot
country: China
facility: Inner Mongolia People's Hospital
state: Inner Mongolia
city: Huai'an
country: China
facility: Huai'an First People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Xi'an
country: China
facility: Shaanxi Provincial People' Hospital
state: Shaanxi
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Weifang
country: China
facility: Weifang People's Hospital
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Shanghai
country: China
facility: Tongji Hospital of Tongji University
state: Shanghai
city: Cheng Du
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Jiaxing
country: China
facility: The First Hospital of Jiaxing
state: Zhejiang/nanhu
city: Hangzhou City
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Ningbo
country: China
facility: The first affiliated hospital of Ningbo university
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Beijing
country: China
facility: Peking University Third Hospital
city: Shenyang
country: China
facility: First Affiliated Hospital of China Medical University
city: Ostrava - Poruba
country: Czechia
facility: Fakultní nemocnice Ostrava
state: Moravskoslezský KRAJ
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
state: Moravskoslezský KRAJ
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
state: Olomoucký KRAJ
city: Pardubice
country: Czechia
facility: Multiscan
state: Pardubický KRAJ
city: PRague
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
state: Praha 10
city: Prague
country: Czechia
facility: Urocentrum Praha
state: Praha 2
city: Prague
country: Czechia
facility: Fakultni Thomayerova nemocnice
state: Praha 4
city: Næstved
country: Denmark
facility: Næstved Sygehus
state: Sjælland
city: Vejle
country: Denmark
facility: Vejle Sygehus
state: Syddanmark
city: Tampere
country: Finland
facility: Tampereen yliopistollinen sairaala
state: Pirkanmaa
city: Oulu
country: Finland
facility: Oulun yliopistollinen sairaala
state: Pohjois-pohjanmaa
city: Kuopio
country: Finland
facility: Kuopion Yliopistollinen Sairaala
state: Pohjois-savo
city: Turku
country: Finland
facility: Turku University Hospital
state: Varsinais-suomi
city: Helsinki
country: Finland
facility: Helsinki university hospital
city: Strasbourg
country: France
facility: Institut de cancérologie Strasbourg Europe (ICANS)
state: Alsace
city: Bordeaux
country: France
facility: Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
state: Aquitaine
city: Brest
country: France
facility: CHRU de Brest
state: Finistère
city: Saint Grégoire
country: France
facility: Centre Hospitalier Privé Saint-Grégoire
state: Ille-et-vilaine
city: Saint Herblain
country: France
facility: Institut de Cancérologie de l'Ouest
state: Loire-atlantique
city: Reims
country: France
facility: Institut Jean Godinot
state: Marne
city: Le Mans
country: France
facility: Clinique Victor Hugo Le Mans
state: Pays-de-la-loire
city: Lyon Cedex08
country: France
facility: Centre Leon Berard
state: Rhône-alpes
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
state: Rhône
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne
city: Reims
country: France
facility: Institut Godinot
city: Nürtingen
country: Germany
facility: Studienpraxis Urologie
state: Baden-württemberg
city: Tübingen
country: Germany
facility: Universitaetsklinikum Tuebingen
state: Baden-württemberg
city: Münster
country: Germany
facility: Universitätsklinikum Münster - Albert Schweitzer Campus
state: Nordrhein-westfalen
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Patras
country: Greece
facility: University Hospital of Patras
state: Achaḯa
city: Athens
country: Greece
facility: Alexandra General Hospital of Athens
state: Attikí
city: Athens
country: Greece
facility: Athens Medical Center
state: Attikí
city: Chaidari
country: Greece
facility: Attikon General University Hospital
state: Attikí
city: Larissa
country: Greece
facility: University General Hospital of Larissa
state: Thessalía
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Vármegyei Központi Kórház és Egyetemi Oktatókórház
state: Borsod-abaúj-zemplén
city: Gyor
country: Hungary
facility: Petz Aladar Egyetemi Oktato Korhaz
state: Győr-moson-sopron
city: Meldola
country: Italy
facility: IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"
state: Emilia-romagna
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
state: Lazio
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
state: Lazio
city: Cremona
country: Italy
facility: Azienda Socio Sanitaria Territoriale di Cremona
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria Terni
city: Trento
country: Italy
facility: APSS- Presidio Ospedaliero S. Chiara
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma
city: Chiba-shi
country: Japan
facility: Chiba cancer center
state: Chiba
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Sapporo
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
state: Hokkaido
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kobe
country: Japan
facility: Kobe University Hospital
state: Hyogo
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
state: Ishikawa
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center
state: Kanagawa
city: Yokosuka
country: Japan
facility: Yokosuka Kyosai Hospital
state: Kanagawa
city: Suita
country: Japan
facility: The University of Osaka Hospital
state: Osaka
city: Shinjuku-ku
country: Japan
facility: Keio university hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Kumamoto
country: Japan
facility: National Hospital Organization Kumamoto Medical Center
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Yamagata
country: Japan
facility: Yamagata University Hospital
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeonranamdo
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Kyǒnggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul-teukbyeolsi [seoul]
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Seoul-teukbyeolsi [seoul]
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul-teukbyeolsi [seoul]
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul-teukbyeolsi [seoul]
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
state: Taegu-kwangyǒkshi
city: Jung-gu
country: Korea, Republic of
facility: Chungnam national university hospital
state: Taejǒn-kwangyǒkshi
city: Tauranga
country: New Zealand
facility: Tauranga Hospital
state: BAY OF Plenty
city: Torun
country: Poland
facility: MICS Centrum Medyczne Torun
state: Kujawsko-pomorskie
city: Lublin
country: Poland
facility: Clinical Best Solutions
state: Lubelskie
city: Kraków
country: Poland
facility: Centrum Badań Klinicznych Jagiellońskie Centrum Innowacji sp. z o.o.
state: Małopolskie
city: Kraków
country: Poland
facility: Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie
state: Małopolskie
city: Piotrków Trybunalski
country: Poland
facility: Provita Profamilia
state: Łódzkie
city: Bratislava
country: Slovakia
facility: CUIMED, s.r.o., Urologicka ambulancia
city: Martin
country: Slovakia
facility: Univerzitna nemocnica Martin
city: Trencin
country: Slovakia
facility: Privatna urologicka ambulancia, s.r.o.
city: Port Elizabeth
country: South Africa
facility: Cancercare Langenhoven Drive Oncology Centre
state: Eastern CAPE
city: Pretoria
country: South Africa
facility: Wilgers Oncology Centre
state: Gauteng
city: Soweto
country: South Africa
facility: Wits Clinical Research
state: Gauteng
city: George
country: South Africa
facility: TASK Eden
state: Western CAPE
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Madrid, Comunidad DE
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología
state: Valenciana, Comunitat
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Stockholm
country: Sweden
facility: Södersjukhuset
state: Stockholms LÄN [se-01]
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: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: İstanbul
country: Turkey
facility: Koç Üniversitesi Hastanesi
state: İ̇stanbul
city: Ankara
country: Turkey
facility: Sbü Gülhane Eğitim Ve Araştirma Hastanesi
city: Ankara
country: Turkey
facility: Memorial Ankara Hastanesi
city: Blackburn
country: United Kingdom
facility: Royal Blackburn Hospital
state: Blackburn WITH Darwen
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: