OP-1250 (Palazestrant) vs. Standard of Care for the Treatment of ER+/HER2- Advanced Breast Cancer

Breast Cancer Clinical Trial

— OPERA-01  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06016738
• Other study ID #: OP-1250-301
• Secondary ID: OPERA-01
• Status: Recruiting
• Phase: Phase 3
• Start date: November 16, 2023
• Est. completion date: September 30, 2027

Study information

• Verified date: May 2024
• Source: Olema Pharmaceuticals, Inc.
• Contact: Olema Pharmaceuticals, Inc.
• Phone: 415-651-7206
• Email: OPERA-01[@]olema.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 510
• Est. completion date: September 30, 2027
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Cancer
• Breast Neoplasms
• ER Positive Breast Cancer
• HER2 Negative Breast Carcinoma
• Metastatic Breast Cancer

Intervention

Drug:
• Palazestrant
Participants will be treated with palazestrant once daily on a 4 week (28 day) cycle. Doses evaluated in the dose-selection part will be 120 mg once daily and 90 mg once daily.
• Fulvestrant
Participants will be treated with fulvestrant on C1D1, C1D15, and then on Day 1 of every subsequent 4 week (28 day) cycle
• Anastrozole
Participants will be treated with anastrozole once daily on a 4 week (28 day) cycle
• Letrozole
Participants will be treated with letrozole once daily on a 4 week (28 day) cycle
• Exemestane
Participants will be treated with exemestane once daily on a 4 week (28 day) cycle

Locations

Country	Name	City	State
Argentina	Clinical Trial Site	Buenos Aires
Argentina	Clinical Trial Site	La Rioja
Argentina	Clinical Trial Site	Rosario	Santa Fe
Argentina	Clinical Trial Site	Rosario	Santa Fe
Australia	Clinical Trial Site	Adelaide	South Australia
Australia	Clinical Trial Site	Ballarat Central	Victoria
Australia	Clinical Trial Site	Clayton	Victoria
Australia	Clinical Trial Site	Gosford	New South Wales
Australia	Clinical Trial Site	Nedlands	Western Australia
Australia	Clinical Trial Site	Shepparton	Victoria
Australia	Clinical Trial Site	Westmead	New South Wales
Belgium	Clinical Trial Site	Charleroi	Hainaut
Belgium	Clinical Trial Site	Leuven	Vlaams Brabant
Hong Kong	Clinical Trial Site	Central
Hong Kong	Clinical Trial Site	Central
Hong Kong	Clinical Trial Site	Hong Kong
Hong Kong	Clinical Trial Site	Kowloon
Italy	Clinical Trial Site	Meldola	Emilia-Romagna
Korea, Republic of	Clinical Trial Site	Busan
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Suwon
Korea, Republic of	Clinical Trial Site	Suwon-si	Gyeonggi-do
Malaysia	Clinical Trial Site	George Town	Penang
Malaysia	Clinical Trial Site	Ipoh	Perak
Malaysia	Clinical Trial Site	Kota Bharu	Kelantan
Malaysia	Clinical Trial Site	Kuala Lumpur	WP
Malaysia	Clinical Trial Site	Kuching	Sarawak
Malaysia	Clinical Trial Site	Petaling Jaya	Selangor
Malaysia	Clinical Trial Site	Putrajaya	Putramya
Portugal	Clinical Trial Site	Lisboa
Portugal	Clinical Trial Site	Matosinhos	Porto
Portugal	Clinical Trial Site	Porto
Taiwan	Clinical Trial Site	Changhua
Taiwan	Clinical Trial Site	Kaohsiung
Taiwan	Clinical Trial Site	Taichung
Taiwan	Clinical Trial Site	Taichung
Taiwan	Clinical Trial Site	Tainan City
Taiwan	Clinical Trial Site	Taipei
Taiwan	Clinical Trial Site	Taipei city
Thailand	Clinical Trial Site	Bangkok
Thailand	Clinical Trial Site	Bangkok
Thailand	Clinical Trial Site	Bangkok
Thailand	Clinical Trial Site	Chiang Mai
Thailand	Clinical Trial Site	Samut Sakhon
Thailand	Clinical Trial Site	Songkhla
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Danbury	Connecticut
United States	Clinical Trial Site	Farmington	New Mexico
United States	Clinical Trial Site	Fountain Valley	California
United States	Clinical Trial Site	Grand Junction	Colorado
United States	Clinical Trial Site	Los Angeles	California
United States	Clinical Trial Site	Margate	Florida
United States	Clinical Trial Site	Orlando	Florida
United States	Clinical Trial Site	Port Jefferson Station	New York
United States	Clinical Trial Site	Spokane	Washington
United States	Clinical Trial Site	Spokane	Washington
United States	Clinical Trial Site	Toledo	Ohio
United States	Clinical Trial Site	Urbana	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Olema Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Hong Kong,  Italy,  Korea, Republic of,  Malaysia,  Portugal,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-Selection Part: Incidence of adverse events	To evaluate the number of participants with adverse events	From Date of Randomization up to 16 weeks
Primary	Dose-Selection Part: Incidence of dose reduction	To evaluate the number of participants reducing the dose of palazestrant	From Date of Randomization up to 16 weeks
Primary	Dose-Selection Part: Incidence of drug discontinuation	To evaluate the number of participants discontinuing palazestrant	From Date of Randomization up to 16 weeks
Primary	Trial: Progression-Free Survival (PFS)	To compare PFS, based on a Blinded Independent Review Committee (BIRC) assessment, between arms of OP-1250 and standard-of-care treatment. This will be assessed separately in populations of ESR1-mutation detected and ESR1-mutation not detected participants.	From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 2 years)
Secondary	Trial: Overall Survival (OS)	To compare OS between arms of OP-1250 and standard-of-care treatment. This will be assessed separately in populations of ESR1 mutation detected and ESR1 mutation not detected participants.	From Date of Randomization until Death Due to Any Cause (estimated as up to 4 years)

External Links

•   Olema Publications