Sponsor: Olema Pharmaceuticals, Inc. (industry)
Phase: 3
Start date: Nov. 16, 2023
Planned enrollment: 510
Palazestrant, also known as OP-1250, is an investigational oral therapy developed for the treatment of estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2–) advanced or metastatic breast cancer. It functions as a complete estrogen receptor antagonist (CERAN) and selective estrogen receptor degrader (SERD), aiming to overcome resistance mechanisms associated with current endocrine therapies.
Palazestrant binds to the estrogen receptor, completely blocking estrogen-induced transcriptional activity without any agonist effects. This complete antagonism leads to the degradation of the receptor, effectively inhibiting the proliferation of ER+ breast cancer cells, including those harboring ESR1 mutations that confer resistance to other endocrine therapies. (aacrjournals.org)
In a Phase 2 clinical study involving 86 heavily pretreated patients with ER+/HER2– metastatic breast cancer, palazestrant demonstrated promising results:
Palazestrant was well tolerated in the Phase 2 study. The most common treatment-emergent adverse events were grade 1 or 2, with no grade 4 events observed. Notably, neutropenia was reversible in all patients, and its timing was consistent with expectations for ribociclib-related neutropenia when used in combination therapy. (globenewswire.com)
Last updated: Aug 2025
As of June 2024, there are no published early results or clinical data specifically from the OPERA-01 (NCT06016738) trial. The sponsor, Olema Oncology, has issued press releases announcing the launch of the trial and describing its purpose in the treatment landscape for ER+, HER2- advanced or metastatic breast cancer following progression on endocrine and CDK4/6 inhibitor therapy. No interim efficacy or safety updates from this specific phase 3 trial have been disclosed.
Most public commentary and analysis available relate to the initiation of the OPERA-01 trial and its strategic place as a phase 3 investigation testing OP-1250 monotherapy against physician’s choice standard of care. Trade publications and news outlets, such as FierceBiotech and Endpoints News, have reported on the enrollment of the first patient but have not provided independent analysis beyond summarizing company statements and contextualizing the trial’s goal as part of ongoing efforts to address the unmet need in patients whose disease has progressed after CDK4/6 inhibitors.
Expert interviews or third-party analysis specifically discussing the clinical significance or comparative appeal of participating in OPERA-01, beyond company-sponsored materials, have not been found in current publicly available sources. Most external reporting reiterates the trial’s aim to potentially provide a new therapeutic option for a patient population with limited current alternatives post-CDK4/6 inhibition.
Reports on patient interest, advocacy perspectives, or real-world reactions to the OPERA-01 trial have not appeared in major news outlets, cancer forums, or social media channels as of this date.
No additional independent analysis, early results, or patient/oncologist perspectives specific to OPERA-01 are available at this time.
Last updated: Aug 2025
Goal: To compare the safety and efficacy of palazestrant (OP-1250) monotherapy with standard-of-care endocrine therapy in patients with ER+, HER2- advanced or metastatic breast cancer that has progressed following prior endocrine therapy and CDK4/6 inhibitor treatment.
Patients: Adult women and men with ER+, HER2- advanced or metastatic breast cancer whose disease is not amenable to curative therapy, has relapsed or progressed on 1 or 2 lines of standard endocrine therapy (including a CDK4/6 inhibitor), with good performance status and adequate organ function. Key exclusions include symptomatic visceral disease, prior chemotherapy in the advanced/metastatic setting, prior investigational ER-targeted therapy, and active brain or leptomeningeal metastases.
Design: This is an international, multicenter, randomized, open-label, active-controlled phase 3 study. About 510 participants are randomized to receive either palazestrant or standard-of-care endocrine therapy. The trial includes an initial dose-selection phase followed by the main efficacy phase.
Treatments: The investigational arm is palazestrant (OP-1250), an oral complete estrogen receptor antagonist (CERAN) and SERD that fully blocks estrogen receptor signaling and induces receptor degradation, including in cases with ESR1 mutations. In prior phase 2 studies, palazestrant showed a median progression-free survival of 4.6-7.2 months and clinical benefit rates between 40-59% depending on the subgroup, with a favorable safety profile. The control arm is standard-of-care endocrine therapy, consisting of either fulvestrant or an aromatase inhibitor (anastrozole, letrozole, or exemestane).
Outcomes: Primary endpoints include progression-free survival (PFS) by BIRC and safety/tolerability measures (incidence of adverse events, dose reductions, and drug discontinuations) during the dose-selection phase. Secondary outcomes include overall survival (OS). Efficacy is assessed separately for participants with and without ESR1 mutations.
Burden on patient: The patient burden for this trial is expected to be low to moderate. Both palazestrant and standard therapies are oral or parenteral agents commonly used in this setting, and additional procedures beyond standard oncologic care (such as routine imaging, labs, and clinical assessments) are not detailed. No mention is made of mandated biopsies or intensive PK sampling. Travel requirements should be similar to routine clinical follow-up. Overall, the trial procedures align with current standards for metastatic breast cancer clinical trials.
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.
San Salvador De Jujuy, Jujuy, 4600, Argentina
No email / No phone
Status: Recruiting
Viedma, Río Negro, R8500ACE, Argentina
No email / No phone
Status: Recruiting
Rosario, Santa Fe, S2013DTC, Argentina
No email / No phone
Status: Recruiting
Rosario, Santa Fe, S2013KDS, Argentina
No email / No phone
Status: Recruiting
San Miguel De Tucumán, Tucumán, 4000, Argentina
No email / No phone
Status: Recruiting
Buenos Aires, C14626ABP, Argentina
No email / No phone
Status: Recruiting
La Rioja, 5300, Argentina
No email / No phone
Status: Recruiting
Córdoba, X5008HHW, Argentina
No email / No phone
Status: Recruiting
Córdoba, X5000HHW, Argentina
No email / No phone
Status: Recruiting
Westmead, New South Wales, 2145, Australia
No email / No phone
Status: Recruiting
Gosford, New South Wales, 2250, Australia
No email / No phone
Status: Recruiting
Adelaide, South Australia, 5000, Australia
No email / No phone
Status: Recruiting
Shepparton, Victoria, 3630, Australia
No email / No phone
Status: Recruiting
Clayton, Victoria, 3168, Australia
No email / No phone
Status: Recruiting
Ballarat Central, Victoria, 3355, Australia
No email / No phone
Status: Recruiting
Nedlands, Western Australia, 6009, Australia
No email / No phone
Status: Recruiting
Edegem, Antwerpen, 2650, Belgium
No email / No phone
Status: Recruiting
Woluwe-Saint-Lambert, Brussels, 1200, Belgium
No email / No phone
Status: Recruiting
Charleroi, Hainaut, 6000, Belgium
No email / No phone
Status: Recruiting
Leuven, Vlaams Brabant, Belgium
No email / No phone
Status: Recruiting
Salvador, Bahia, 40050-410, Brazil
No email / No phone
Status: Recruiting
Belo Horizonte, Minas Gerais, 30150-221, Brazil
No email / No phone
Status: Recruiting
Recife, Pernambuco, 50070-480, Brazil
No email / No phone
Status: Recruiting
Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
No email / No phone
Status: Recruiting
Porto Alegre, Rio Grande do Sul, 90050-170, Brazil
No email / No phone
Status: Recruiting
Itajaí, Santa Catarina, 88301-220, Brazil
No email / No phone
Status: Recruiting
Sorocaba, São Paulo, 18060-105, Brazil
No email / No phone
Status: Recruiting
Rio De Janeiro, 20560-120, Brazil
No email / No phone
Status: Recruiting
Panagyurishte, Pazardzhik, 4500, Bulgaria
No email / No phone
Status: Recruiting
Sofia, Sofia-Grad, 1407, Bulgaria
No email / No phone
Status: Recruiting
Vratsa, 3000, Bulgaria
No email / No phone
Status: Recruiting
Calgary, Alberta, T2N 4N2, Canada
No email / No phone
Status: Recruiting
Montréal, Quebec, H4A 3J1, Canada
No email / No phone
Status: Recruiting
Hradec Králové, Královéhradecký kraj, 500 12, Czechia
No email / No phone
Status: Recruiting
Nový Jičín, Moravskoslezský kraj, 741 01, Czechia
No email / No phone
Status: Recruiting
Olomouc, Olomoucký kraj, 799 00, Czechia
No email / No phone
Status: Recruiting
Bourg-en-Bresse, Ain, 01012, France
No email / No phone
Status: Recruiting
Besançon, Doubs, 25030, France
No email / No phone
Status: Recruiting
Nantes, Loire-Atlantique, 44805, France
No email / No phone
Status: Recruiting
Compiègne, Oise, 60200, France
No email / No phone
Status: Recruiting
Clermont-Ferrand, Puy-de-Dôme, 63011, France
No email / No phone
Status: Recruiting
Le Mans, Sarthe, 72015, France
No email / No phone
Status: Recruiting
Villejuif, Val-de-Marne, 94085, France
No email / No phone
Status: Recruiting
Montpellier, 34070, France
No email / No phone
Status: Recruiting
Karlsruhe, Baden-Württemberg, 76135, Germany
No email / No phone
Status: Recruiting
Velbert, Nordrhein-Westfalen, 42551, Germany
No email / No phone
Status: Recruiting
Krefeld, Nordrhein-Westfalen, 47805, Germany
No email / No phone
Status: Recruiting
Dresden, Sachsen, 01307, Germany
No email / No phone
Status: Recruiting
Kowloon, 999077, Hong Kong
No email / No phone
Status: Recruiting
Hong Kong, 999077, Hong Kong
No email / No phone
Status: Recruiting
Central, 100176, Hong Kong
No email / No phone
Status: Recruiting
Central, 999077, Hong Kong
No email / No phone
Status: Recruiting
Hong Kong, 999077, Hong Kong
No email / No phone
Status: Recruiting
Kecskemét, Bács-Kiskun, 6000, Hungary
No email / No phone
Status: Recruiting
Pécs, Baranya, 7624, Hungary
No email / No phone
Status: Recruiting
Debrecen, Hajdú-Bihar, 4032, Hungary
No email / No phone
Status: Recruiting
Avellino, Campania, 83100, Italy
No email / No phone
Status: Recruiting
Modena, Emilia-Romagna, 41124, Italy
No email / No phone
Status: Recruiting
Bologna, Emilia-Romagna, 40138, Italy
No email / No phone
Status: Recruiting
Meldola, Emilia-Romagna, 47014, Italy
No email / No phone
Status: Recruiting
Reggio Emilia, Emilia-Romagna, 42100, Italy
No email / No phone
Status: Recruiting
Udine, Friuli-Venezia Giulia, 33100, Italy
No email / No phone
Status: Recruiting
Roma, Lazio, 00168, Italy
No email / No phone
Status: Recruiting
Roma, Lazio, 00144, Italy
No email / No phone
Status: Recruiting
Rozzano, Lombardia, 20089, Italy
No email / No phone
Status: Recruiting
Milano, Lombardia, 20141, Italy
No email / No phone
Status: Recruiting
Alessandria, Piemonte, 15121, Italy
No email / No phone
Status: Recruiting
Pavia, 27100, Italy
No email / No phone
Status: Recruiting
Suwon-si, Gyeonggi-do, 16247, Korea, Republic of
No email / No phone
Status: Recruiting
Seoul, 3722, Korea, Republic of
No email / No phone
Status: Recruiting
Suwon, 16499, Korea, Republic of
No email / No phone
Status: Recruiting
Seoul, 8308, Korea, Republic of
No email / No phone
Status: Recruiting
Seoul, 6591, Korea, Republic of
No email / No phone
Status: Recruiting
Seoul, 2841, Korea, Republic of
No email / No phone
Status: Recruiting
Busan, 49201, Korea, Republic of
No email / No phone
Status: Recruiting
Seoul, 5505, Korea, Republic of
No email / No phone
Status: Recruiting
Seoul, 6273, Korea, Republic of
No email / No phone
Status: Recruiting
Seoul, 3080, Korea, Republic of
No email / No phone
Status: Recruiting
Sungai Petani, Kedah, 8000, Malaysia
No email / No phone
Status: Recruiting
Kota Bharu, Kelantan, 16150, Malaysia
No email / No phone
Status: Recruiting
George Town, Penang, 10450, Malaysia
No email / No phone
Status: Recruiting
Ipoh, Perak, 30450, Malaysia
No email / No phone
Status: Recruiting
Putrajaya, Putramya, 62250, Malaysia
No email / No phone
Status: Recruiting
Kuching, Sarawak, 93586, Malaysia
No email / No phone
Status: Recruiting
Petaling Jaya, Selangor, 46050, Malaysia
No email / No phone
Status: Recruiting
Kuala Lumpur, WP, 59100, Malaysia
No email / No phone
Status: Recruiting
Zapopan, Jalisco, 45070, Mexico
No email / No phone
Status: Recruiting
Monterrey, 64116, Mexico
No email / No phone
Status: Recruiting
Oaxaca, 68020, Mexico
No email / No phone
Status: Recruiting
Sinaloa, 80230, Mexico
No email / No phone
Status: Recruiting
Rotterdam, Zuid-Holland, 3083 AN, Netherlands
No email / No phone
Status: Recruiting
Łódź, Lódzkie, 90-349, Poland
No email / No phone
Status: Recruiting
Otwock, Mazowieckie, 05-400, Poland
No email / No phone
Status: Recruiting
Rzeszów, Podkarpackie, 35-922, Poland
No email / No phone
Status: Recruiting
Brzozów, Podkarpackie, 36-200, Poland
No email / No phone
Status: Recruiting
Gdynia, Pomorskie, 81-519, Poland
No email / No phone
Status: Recruiting
Skórzewo, Wielkopolskie, 60-185, Poland
No email / No phone
Status: Recruiting
Wrocław, 50-450, Poland
No email / No phone
Status: Recruiting
Matosinhos, Porto, 4454-509, Portugal
No email / No phone
Status: Recruiting
Porto, 4050-428, Portugal
No email / No phone
Status: Recruiting
Coimbra, 3000-075, Portugal
No email / No phone
Status: Recruiting
Lisboa, 1099-023, Portugal
No email / No phone
Status: Recruiting
Lisboa, 1500-473, Portugal
No email / No phone
Status: Recruiting
Mayaguez, 00682-6391, Puerto Rico
No email / No phone
Status: Recruiting
Oradea, Bihor, 410469, Romania
No email / No phone
Status: Recruiting
București, Bucuresti, 014141, Romania
No email / No phone
Status: Recruiting
Cluj-Napoca, Cluj, 400015, Romania
No email / No phone
Status: Recruiting
Craiova, Dolj, 200385, Romania
No email / No phone
Status: Recruiting
Timisoara, Timis, 300239, Romania
No email / No phone
Status: Recruiting
Iași, 700106, Romania
No email / No phone
Status: Recruiting
Brașov, 500152, Romania
No email / No phone
Status: Recruiting
Pamplona, Navarra, 31008, Spain
No email / No phone
Status: Recruiting
León, 24071, Spain
No email / No phone
Status: Recruiting
Alicante, 03015, Spain
No email / No phone
Status: Recruiting
Badajoz, 06080, Spain
No email / No phone
Status: Recruiting
Lleida, 25198, Spain
No email / No phone
Status: Recruiting
Madrid, 28033, Spain
No email / No phone
Status: Recruiting
Madrid, 28050, Spain
No email / No phone
Status: Recruiting
Santiago De Compostela, 15706, Spain
No email / No phone
Status: Recruiting
Valencia, 46010, Spain
No email / No phone
Status: Recruiting
Taichung, 40447, Taiwan
No email / No phone
Status: Recruiting
Taipei, 11217, Taiwan
No email / No phone
Status: Recruiting
Taipei, 100, Taiwan
No email / No phone
Status: Recruiting
Taipei city, 114, Taiwan
No email / No phone
Status: Recruiting
Taipei city, 111, Taiwan
No email / No phone
Status: Recruiting
Tainan City, 736, Taiwan
No email / No phone
Status: Recruiting
Taichung, 433, Taiwan
No email / No phone
Status: Recruiting
Changhua, 500, Taiwan
No email / No phone
Status: Recruiting
Kaohsiung, 80756, Taiwan
No email / No phone
Status: Recruiting
Bangkok, 10300, Thailand
No email / No phone
Status: Recruiting
Songkhla, 90110, Thailand
No email / No phone
Status: Recruiting
Samut Sakhon, 74120, Thailand
No email / No phone
Status: Recruiting
Chiang Mai, 50180, Thailand
No email / No phone
Status: Recruiting
Bangkok, 10700, Thailand
No email / No phone
Status: Recruiting
Bangkok, 10330, Thailand
No email / No phone
Status: Recruiting
London, EC1M 6BQ, United Kingdom
No email / No phone
Status: Recruiting
Tucson, Arizona, 85724, United States
No email / No phone
Status: Recruiting
La Jolla, California, 92093, United States
No email / No phone
Status: Recruiting
Fountain Valley, California, 92708, United States
No email / No phone
Status: Recruiting
Los Angeles, California, 90027, United States
No email / No phone
Status: Recruiting
Whittier, California, 90602, United States
No email / No phone
Status: Recruiting
Grand Junction, Colorado, 81505, United States
No email / No phone
Status: Recruiting
Golden, Colorado, 80401, United States
No email / No phone
Status: Recruiting
Denver, Colorado, 80218, United States
No email / No phone
Status: Recruiting
Aurora, Colorado, 80045, United States
No email / No phone
Status: Recruiting
Danbury, Connecticut, 06810, United States
No email / No phone
Status: Recruiting
Newark, Delaware, 19713, United States
No email / No phone
Status: Recruiting
Plantation, Florida, 33324, United States
No email / No phone
Status: Recruiting
Orlando, Florida, 32804, United States
No email / No phone
Status: Recruiting
Margate, Florida, 33063, United States
No email / No phone
Status: Recruiting
Jacksonville, Florida, 32223, United States
No email / No phone
Status: Recruiting
Tamarac, Florida, 33321, United States
No email / No phone
Status: Recruiting
Atlanta, Georgia, 30322, United States
No email / No phone
Status: Recruiting
Chicago, Illinois, 60616-2315, United States
No email / No phone
Status: Recruiting
Chicago, Illinois, 60637, United States
No email / No phone
Status: Recruiting
Urbana, Illinois, 61801, United States
No email / No phone
Status: Recruiting
Baton Rouge, Louisiana, 70809, United States
No email / No phone
Status: Recruiting
Baltimore, Maryland, 21201, United States
No email / No phone
Status: Recruiting
Boston, Massachusetts, 02111, United States
No email / No phone
Status: Recruiting
St Louis Park, Minnesota, 55426, United States
No email / No phone
Status: Recruiting
Lincoln, Nebraska, 68510-2496, United States
No email / No phone
Status: Recruiting
Farmington, New Mexico, 87401, United States
No email / No phone
Status: Recruiting
New York, New York, 10032, United States
No email / No phone
Status: Recruiting
Port Jefferson Station, New York, 11776, United States
No email / No phone
Status: Recruiting
Dayton, Ohio, 45409, United States
No email / No phone
Status: Recruiting
Toledo, Ohio, 43623, United States
No email / No phone
Status: Recruiting
Portland, Oregon, 97239, United States
No email / No phone
Status: Recruiting
Nashville, Tennessee, 37203, United States
No email / No phone
Status: Recruiting
Nashville, Tennessee, 37208, United States
No email / No phone
Status: Recruiting
Houston, Texas, 77030, United States
No email / No phone
Status: Recruiting
Dallas, Texas, 75390, United States
No email / No phone
Status: Recruiting
Dallas, Texas, 75246, United States
No email / No phone
Status: Recruiting
Spokane, Washington, 99218, United States
No email / No phone
Status: Recruiting
Spokane, Washington, 99204, United States
No email / No phone
Status: Recruiting