OP-1250 (Palazestrant) vs. Standard of Care for the Treatment of ER+/HER2- Advanced Breast Cancer (OPERA-01)

Olema Pharmaceuticals

Status and phase: Active, not recruiting; Phase 3

Conditions: Breast Cancer; ER Positive Breast Cancer; HER2 Negative Breast Carcinoma; Metastatic Breast Cancer; Advanced Breast Cancer

Treatments: Drug: Letrozole; Drug: Exemestane; Drug: Anastrozole; Drug: Fulvestrant; Drug: Palazestrant

Study type: Interventional

Funder types: Industry

Identifiers

NCT06016738

OP-1250-301

OPERA-01 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 510 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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510 participants in 2 patient groups

Palazestrant (OP-1250)

Experimental group

Description:

Participants will receive Palazestrant

Treatment:

Drug: Palazestrant

Standard of Care Endocrine Therapy

Active Comparator group

Description:

Participants will receive Investigator's choice of one of the Standard of Care drugs (fulvestrant, anastrozole, letrozole, or exemestane)

Treatment:

Drug: Fulvestrant

Drug: Anastrozole

Drug: Exemestane

Drug: Letrozole