Palazestrant in Combination With Ribociclib for the First-line Treatment of ER+/HER2- Advanced Breast Cancer (OPERA-02)

Olema Pharmaceuticals

Status and phase: Begins enrollment in 2 months; Phase 3

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

Treatments: Drug: Palazestrant; Drug: Palazestrant matching-placebo; Drug: Letrozole; Drug: Ribociclib; Drug: Letrozole-matching placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07085767

OP-1250-302

OPERA-02 (Other Identifier)

Details and patient eligibility

About

This phase 3 clinical trial compares the efficacy and safety of palazestrant with ribociclib to letrozole and ribociclib in women and men who have not received prior systemic anti-cancer treatment for advanced breast cancer.

Full description

This is an international, multicenter, randomized, double-blind, active-controlled, phase 3 clinical trial. The purpose of this trial is to compare the efficacy and safety of palazestrant in combination with ribociclib +letrozole -matching placebo (Arm A: investigational arm) with letrozole in combination with ribociclib + palazestrant-matching placebo (Arm B: control arm).

This trial is seeking adult participants with ER+, HER2- advanced breast cancer who have not received prior systemic anti-cancer treatment for advanced disease. Approximately 1,000 participants will be randomized in a 1:1 ratio to one of the two study arms.

Enrollment: 1,000 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 per RECIST 1.1 or bone-only disease).
• De novo advanced breast cancer or with disease recurrence occurring after 12 months of completing adjuvant endocrine therapy (with or without CDK4/6 inhibitors)
• 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.

Exclusion criteria

• Disease recurrence during adjuvant endocrine therapy
• Currently receiving or previously received systemic anti-cancer therapy for ER+, HER2- advanced breast cancer.
• Previously received treatment with fulvestrant, elacestrant or an investigational endocrine therapy in any setting.
• History of allergic reactions to study treatment.
• Any contraindications to letrozole and ribociclib.
• Symptomatic central nervous system metastases, carcinomatous meningitis, leptomeningeal disease, or a spinal cord compression that require immediate treatment.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,000 participants in 2 patient groups

Palazestrant

Experimental group

Description:

Participants will receive palazestrant, ribociclib and letrozole-matching placebo

Treatment:

Drug: Letrozole-matching placebo

Drug: Ribociclib

Drug: Palazestrant

Letrozole

Active Comparator group

Description:

Participants will receive letrozole, ribociclib and palazestrant-matching placebo

Treatment:

Drug: Ribociclib

Drug: Letrozole

Drug: Palazestrant matching-placebo