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

Study Overview
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Brief Summary
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This phase 3 clinical study compares the safety and efficacy of 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 at least one endocrine therapy in combination with a CDK4/6 inhibitor.

Detailed Description
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This is an international, multicenter, randomized, open-label, active-controlled, phase 3 clinical trial comparing the safety and efficacy of OP-1250 as a single agent to standard of care endocrine therapy of either fulvestrant or an aromatase inhibitor (anastrozole, letrozole, or exemestane) in 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 have included at least one line of endocrine therapy in combination with a CDK 4/6 inhibitor.

Official Title
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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)

Conditions
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Breast Cancer, Advanced Breast Cancer, Metastatic Breast Cancer, ER Positive Breast Cancer, HER2 Negative Breast Carcinoma

Intervention / Treatment
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* Drug: OP-1250
* Drug: Fulvestrant
* Drug: Anastrozole
* Drug: Letrozole
* Drug: Exemestane


Participation Criteria
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Eligibility Criteria
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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 will be allowed. 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 (LHRH) agonist. Key exclusion criteria: Symptomatic visceral disease, imminent organ failure, or any disease burden that makes the participant ineligible for endocrine therapy. Have received prior chemotherapy in the advanced/metastatic setting. Have received prior 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 and others.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OP-1250 (palazestrant)<br>Subjects will receive OP-1250 | Drug: OP-1250<br>* Patients will be treated with OP-1250 once daily on a 4 week (28 day) cycle<br>* Other names: Palazestrant;|
| Active Comparator: Standard of Care Endocrine Therapy<br>Subjects will receive Investigator's choice of one of the Standard of Care drugs (fulvestrant, anastrozole, letrozole, or exemestane) | Drug: Fulvestrant<br>* Patients will be treated with fulvestrant on C1D1, C1D15, and C2D1 in the first 4 week (28 day) cycle, and on Day 1 of every subsequent 4 week (28 day) cycle<br>* Other names: Faslodex;Drug: Anastrozole<br>* Patients will be treated with anastrozole once daily on a 4 week (28 day) cycle<br>* Other names: Arimidex;Drug: Letrozole<br>* Patients will be treated with letrozole once daily on a 4 week (28 day) cycle<br>* Other names: Femara;Drug: Exemestane<br>* Patients will be treated with exemestane once daily on a 4 week (28 day) cycle<br>* Other names: Aromasin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) |