Clinical trial NCT06016738: OP-1250 (Palazestrant) vs. Standard of Care for the Treatment of ER+/HER2- Advanced Breast Cancer
Official title: A Phase 3 Randomized, Open-Label Study of OP-1250 Monotherapy vs Standard of Care for the Treatment of ER+, HER2- Advanced or Metastatic Breast Cancer Following Endocrine and CDK 4/6 Inhibitor Therapy (OPERA-01)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Advanced Breast Cancer
Metastatic Breast Cancer
ER Positive Breast Cancer
HER2 Negative Breast Carcinoma
Lead sponsor: Olema Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-30
Enrollment: 510
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This phase 3 clinical trial compares the safety and efficacy of palazestrant (OP-1250) to the standard-of-care options of fulvestrant or an aromatase inhibitor in women and men with breast cancer whose disease has advanced on one endocrine therapy in combination with a CDK4/6 inhibitor.

Detailed description: This is an international, multicenter, randomized, open-label, active-controlled, phase 3 clinical trial. The purpose of this trial is to compare the safety and efficacy of palazestrant (OP-1250) as a single agent to the standard of care endocrine therapy: either fulvestrant or an aromatase inhibitor (anastrozole, letrozole, or exemestane).

This trial is seeking adult participants with ER+, HER2- advanced or metastatic breast cancer whose disease has relapsed or progressed on 1 or 2 prior lines of standard-of-care endocrine therapy for metastatic breast cancer. Prior lines of therapy must include one line of endocrine therapy in combination with a CDK 4/6 inhibitor. In the dose-selection part of the trial, approximately 120 participants will be randomized to one of the two doses of palazestrant or to the standard-of-care endocrine therapy. Thereafter, approximately 390 participants will be randomized to palazestrant at the selected dose or to the standard-of-care endocrine therapy.

Eligibility criteria: Key inclusion criteria:

* Adult female or male participants.
* ER+, HER2- locally advanced or metastatic breast cancer that is not amenable to curative therapy.
* Evaluable disease (measurable disease or bone-only disease).
* Previously received a CDK4/6 inhibitor in combination with an endocrine therapy in the advanced setting. One additional line of ET as a monotherapy is allowed. Duration of the most recent prior ET must be at least 6 months.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate hematologic, hepatic, and renal functions.
* Female participants can be pre-, peri- or postmenopausal.
* Male and pre- or peri-menopausal female participants must be willing to take a GnRH (or LHRH) agonist.

Key exclusion criteria:

* Symptomatic visceral disease, imminent organ failure, or any other reason that makes the participant ineligible for endocrine monotherapy.
* Previously received chemotherapy in the advanced/metastatic setting.
* Previously received treatment with elacestrant or an investigational estrogen receptor-directed therapy.
* History of allergic reactions to study treatment.
* Any contraindications to the selected standard-of-care endocrine therapy in the local prescribing information.
* Symptomatic central nervous system metastases, carcinomatous meningitis, leptomeningeal disease, or a spinal cord compression that require immediate treatment.
* Clinically significant comorbidities such as significant cardiac or cerebrovascular disease, gastrointestinal disorders that could affect absorption of study treatment.

Primary outcomes:
measure: Dose-Selection Part: Incidence of adverse events
timeFrame: From Date of Randomization up to 16 weeks
measure: Dose-Selection Part: Incidence of dose reduction
timeFrame: From Date of Randomization up to 16 weeks
measure: Dose-Selection Part: Incidence of drug discontinuation
timeFrame: From Date of Randomization up to 16 weeks
measure: Trial: Progression-Free Survival (PFS)
timeFrame: From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 2 years)
Secondary outcomes:
measure: Trial: Overall Survival (OS)
timeFrame: From Date of Randomization until Death Due to Any Cause (estimated as up to 4 years)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Clinical Trial Site
state: Arizona
city: Fountain Valley
country: United States
facility: Clinical Trial Site
state: California
city: La Jolla
country: United States
facility: Clinical Trial Site
state: California
city: Los Angeles
country: United States
facility: Clinical Trial Site
state: California
city: Whittier
country: United States
facility: Clinical Trial Site
state: California
city: Aurora
country: United States
facility: Clinical Trial Site
state: Colorado
city: Denver
country: United States
facility: Clinical Trial Site
state: Colorado
city: Golden
country: United States
facility: Clinical Trial Site
state: Colorado
city: Grand Junction
country: United States
facility: Clinical Trial Site
state: Colorado
city: Danbury
country: United States
facility: Clinical Trial Site
state: Connecticut
city: Newark
country: United States
facility: Clinical Trial Site
state: Delaware
city: Jacksonville
country: United States
facility: Clinical Trials Site
state: Florida
city: Margate
country: United States
facility: Clinical Trial Site
state: Florida
city: Orlando
country: United States
facility: Clinical Trial Site
state: Florida
city: Plantation
country: United States
facility: Clinical Trial Site
state: Florida
city: Tamarac
country: United States
facility: Clinical Trial Site
state: Florida
city: Atlanta
country: United States
facility: Clinical Trial Site
state: Georgia
city: Chicago
country: United States
facility: Clinical Trial Site
state: Illinois
city: Chicago
country: United States
facility: Clinical Trial Site
state: Illinois
city: Urbana
country: United States
facility: Clinical Trial Site
state: Illinois
city: Baton Rouge
country: United States
facility: Clinical Trial Site
state: Louisiana
city: Baltimore
country: United States
facility: Clinical Trial Site
state: Maryland
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: St Louis Park
country: United States
facility: Clinical Trial Site
state: Minnesota
city: Lincoln
country: United States
facility: Clinical Trial Site
state: Nebraska
city: Farmington
country: United States
facility: Clinical Trial Site
state: New Mexico
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Port Jefferson Station
country: United States
facility: Clinical Trial Site
state: New York
city: Dayton
country: United States
facility: Clinical Trial Site
state: Ohio
city: Toledo
country: United States
facility: Clinical Trial Site
state: Ohio
city: Portland
country: United States
facility: Clinical Trial Site
state: Oregon
city: Nashville
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Nashville
country: United States
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state: Tennessee
city: Dallas
country: United States
facility: Clinical Trial Site
state: Texas
city: Dallas
country: United States
facility: Clinical Trial Site
state: Texas
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: Spokane
country: United States
facility: Clinical Trial Site
state: Washington
city: Spokane
country: United States
facility: Clinical Trial Site
state: Washington
city: San Salvador De Jujuy
country: Argentina
facility: Clinical Trial Site
state: Jujuy
city: Viedma
country: Argentina
facility: Clinical Trial Site
state: Río Negro
city: Rosario
country: Argentina
facility: Clinical Trial Site
state: Santa Fe
city: Rosario
country: Argentina
facility: Clinical Trial Site
state: Santa Fe
city: San Miguel De Tucumán
country: Argentina
facility: Clinical Trial Site
state: Tucumán
city: Buenos Aires
country: Argentina
facility: Clinical Trial Site
city: Córdoba
country: Argentina
facility: Clinical Trial Site
city: Córdoba
country: Argentina
facility: Clinical Trial Site
city: La Rioja
country: Argentina
facility: Clinical Trial Site
city: Gosford
country: Australia
facility: Clinical Trial Site
state: New South Wales
city: Westmead
country: Australia
facility: Clinical Trial Site
state: New South Wales
city: Adelaide
country: Australia
facility: Clinical Trial Site
state: South Australia
city: Ballarat Central
country: Australia
facility: Clinical Trial Site
state: Victoria
city: Clayton
country: Australia
facility: Clinical Trial Site
state: Victoria
city: Shepparton
country: Australia
facility: Clinical Trial Site
state: Victoria
city: Nedlands
country: Australia
facility: Clinical Trial Site
state: Western Australia
city: Edegem
country: Belgium
facility: Clinical Trial Site
state: Antwerpen
city: Woluwe-Saint-Lambert
country: Belgium
facility: Clinical Trial Site
state: Brussels
city: Charleroi
country: Belgium
facility: Clinical Trial Site
state: Hainaut
city: Leuven
country: Belgium
facility: Clinical Trial Site
state: Vlaams Brabant
city: Salvador
country: Brazil
facility: Clinical Trial Site
state: Bahia
city: Belo Horizonte
country: Brazil
facility: Clinical Trial Site
state: Minas Gerais
city: Recife
country: Brazil
facility: Clinical Trial Site
state: Pernambuco
city: Porto Alegre
country: Brazil
facility: Clinical Trial Site
state: Rio Grande do Sul
city: Porto Alegre
country: Brazil
facility: Clinical Trial Site
state: Rio Grande do Sul
city: Itajaí
country: Brazil
facility: Clinical Trial Site
state: Santa Catarina
city: Sorocaba
country: Brazil
facility: Clinical Trial Site
state: São Paulo
city: Rio De Janeiro
country: Brazil
facility: Clinical Trial Site
city: Panagyurishte
country: Bulgaria
facility: Clinical Trial Site
state: Pazardzhik
city: Sofia
country: Bulgaria
facility: Clinical Trial Site
state: Sofia-Grad
city: Vratsa
country: Bulgaria
facility: Clinical Trial Site
city: Calgary
country: Canada
facility: Clinical Trial Site
state: Alberta
city: Montréal
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Hradec Králové
country: Czechia
facility: Clinical Trial Site
state: Královéhradecký kraj
city: Nový Jičín
country: Czechia
facility: Clinical Trial Site
state: Moravskoslezský kraj
city: Olomouc
country: Czechia
facility: Clinical Trial Site
state: Olomoucký kraj
city: Bourg-en-Bresse
country: France
facility: Clinical Trial Site
state: Ain
city: Besançon
country: France
facility: Clinical Trial Site
state: Doubs
city: Nantes
country: France
facility: Clinical Trial Site
state: Loire-Atlantique
city: Compiègne
country: France
facility: Clinical Trial Site
state: Oise
city: Clermont-Ferrand
country: France
facility: Clinical Trial Site
state: Puy-de-Dôme
city: Le Mans
country: France
facility: Clinical Trial Site
state: Sarthe
city: Villejuif
country: France
facility: Clinical Trial Site
state: Val-de-Marne
city: Montpellier
country: France
facility: Clinical Trial Site
city: Karlsruhe
country: Germany
facility: Clinical Trial Site
state: Baden-Württemberg
city: Krefeld
country: Germany
facility: Clinical Trial Site
state: Nordrhein-Westfalen
city: Velbert
country: Germany
facility: Clinical Trial Site
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Clinical Trial Site
state: Sachsen
city: Central
country: Hong Kong
facility: Clinical Trial Site
city: Central
country: Hong Kong
facility: Clinical Trial Site
city: Hong Kong
country: Hong Kong
facility: Clinical Trial Site
city: Hong Kong
country: Hong Kong
facility: Clinical Trials Site
city: Kowloon
country: Hong Kong
facility: Clinical Trial Site
city: Pécs
country: Hungary
facility: Clinical Trial Site
state: Baranya
city: Kecskemét
country: Hungary
facility: Clinical Trial Site
state: Bács-Kiskun
city: Debrecen
country: Hungary
facility: Clinical Trial Site
state: Hajdú-Bihar
city: Avellino
country: Italy
facility: Clinical Trial Site
state: Campania
city: Bologna
country: Italy
facility: Clinical Trial Site
state: Emilia-Romagna
city: Meldola
country: Italy
facility: Clinical Trial Site
state: Emilia-Romagna
city: Modena
country: Italy
facility: Clinical Trial Site
state: Emilia-Romagna
city: Reggio Emilia
country: Italy
facility: Clinical Trial Site
state: Emilia-Romagna
city: Udine
country: Italy
facility: Clinical Trial Site
state: Friuli-Venezia Giulia
city: Roma
country: Italy
facility: Clinical Trial Site
state: Lazio
city: Roma
country: Italy
facility: Clinical Trial Site
state: Lazio
city: Milano
country: Italy
facility: Clinical Trial Site
state: Lombardia
city: Rozzano
country: Italy
facility: Clinical Trial Site
state: Lombardia
city: Alessandria
country: Italy
facility: Clinical Trial Site
state: Piemonte
city: Pavia
country: Italy
facility: Clinical Trial Site
city: Suwon-si
country: Korea, Republic of
facility: Clinical Trial Site
state: Gyeonggi-do
city: Busan
country: Korea, Republic of
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Suwon
country: Korea, Republic of
facility: Clinical Trial Site
city: Sungai Petani
country: Malaysia
facility: Clinical Trials Site
state: Kedah
city: Kota Bharu
country: Malaysia
facility: Clinical Trial Site
state: Kelantan
city: George Town
country: Malaysia
facility: Clinical Trial Site
state: Penang
city: Ipoh
country: Malaysia
facility: Clinical Trial Site
state: Perak
city: Putrajaya
country: Malaysia
facility: Clinical Trial Site
state: Putramya
city: Kuching
country: Malaysia
facility: Clinical Trial Site
state: Sarawak
city: Petaling Jaya
country: Malaysia
facility: Clinical Trial Site
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: Clinical Trial Site
state: WP
city: Zapopan
country: Mexico
facility: Clinical Trial Site
state: Jalisco
city: Monterrey
country: Mexico
facility: Clinical Trial Site
city: Oaxaca
country: Mexico
facility: Clinical Trial Site
city: Sinaloa
country: Mexico
facility: Clinical Trial Site
city: Rotterdam
country: Netherlands
facility: Clinical Trial Site
state: Zuid-Holland
city: Łódź
country: Poland
facility: Clinical Trial Site
state: Lódzkie
city: Otwock
country: Poland
facility: Clinical Trial Site
state: Mazowieckie
city: Brzozów
country: Poland
facility: Clinical Trial Site
state: Podkarpackie
city: Rzeszów
country: Poland
facility: Clinical Trial Site
state: Podkarpackie
city: Gdynia
country: Poland
facility: Clinical Trial Site
state: Pomorskie
city: Skórzewo
country: Poland
facility: Clinical Trial Site
state: Wielkopolskie
city: Wrocław
country: Poland
facility: Clinical Trial Site
city: Matosinhos
country: Portugal
facility: Clinical Trial Site
state: Porto
city: Coimbra
country: Portugal
facility: Clinical Trial Site
city: Lisboa
country: Portugal
facility: Clinical Trial Site
city: Lisboa
country: Portugal
facility: Clinical Trial Site
city: Porto
country: Portugal
facility: Clinical Trial Site
city: Mayaguez
country: Puerto Rico
facility: Clinical Trial Site
city: Oradea
country: Romania
facility: Clinical Trial Site
state: Bihor
city: București
country: Romania
facility: Clinical Trial Site
state: Bucuresti
city: Cluj-Napoca
country: Romania
facility: Clinical Trial Site
state: Cluj
city: Craiova
country: Romania
facility: Clinical Trial Site
state: Dolj
city: Timisoara
country: Romania
facility: Clinical Trial Site
state: Timis
city: Brașov
country: Romania
facility: Clinical Trial Site
city: Iași
country: Romania
facility: Clinical Trial Site
city: Pamplona
country: Spain
facility: Clinical Trial Site
state: Navarra
city: Alicante
country: Spain
facility: Clinical Trial Site
city: Badajoz
country: Spain
facility: Clinical Trial Site
city: León
country: Spain
facility: Clinical Trial Site
city: Lleida
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
city: Santiago De Compostela
country: Spain
facility: Clinical Trial Site
city: Valencia
country: Spain
facility: Clinical Trial Site
city: Changhua
country: Taiwan
facility: Clinical Trial Site
city: Kaohsiung
country: Taiwan
facility: Clinical Trial Site
city: Taichung
country: Taiwan
facility: Clinical Trial Site
city: Taichung
country: Taiwan
facility: Clinical Trial Site
city: Tainan City
country: Taiwan
facility: Clinical Trial Site
city: Taipei city
country: Taiwan
facility: Clinical Trial Site
city: Taipei city
country: Taiwan
facility: Clinical Trial Site
city: Taipei
country: Taiwan
facility: Clinical Trial Site
city: Taipei
country: Taiwan
facility: Clinical Trial Site
city: Bangkok
country: Thailand
facility: Clinical Trial Site
city: Bangkok
country: Thailand
facility: Clinical Trial Site
city: Bangkok
country: Thailand
facility: Clinical Trial Site
city: Chiang Mai
country: Thailand
facility: Clinical Trial Site
city: Samut Sakhon
country: Thailand
facility: Clinical Trial Site
city: Songkhla
country: Thailand
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Olema Pharmaceuticals, Inc.
name: Medical Director, MD
role: STUDY_DIRECTOR
References: