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

Not Applicable

Not yet recruiting

• Conditions: Breast Cancer; Locally Advanced Breast Cancer; Metastatic Breast Cancer; ER Positive Breast Cancer; HER2 Negative Breast Carcinoma
• Interventions: Drug: Palazestrant; Drug: Letrozole-matching placebo; Drug: Letrozole; Drug: Ribociclib; Drug: Palazestrant matching-placebo

• Registration Number: NCT07085767
• Lead Sponsor: Olema Pharmaceuticals, Inc.

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2025-07-08
• Study First Submitted QC: 2025-07-18
• Study First Posted: 2025-07-25
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-30
• Last Update Posted: 2025-10-01
• Study Start: 2025-10-31
• Primary Completion: 2028-12
• Study Completion: 2032-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 1000

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Palazestrant	Palazestrant	Participants will receive palazestrant, ribociclib and letrozole-matching placebo
Palazestrant	Letrozole-matching placebo	Participants will receive palazestrant, ribociclib and letrozole-matching placebo
Palazestrant	Ribociclib	Participants will receive palazestrant, ribociclib and letrozole-matching placebo
Letrozole	Ribociclib	Participants will receive letrozole, ribociclib and palazestrant-matching placebo
Letrozole	Palazestrant matching-placebo	Participants will receive letrozole, ribociclib and palazestrant-matching placebo
Letrozole	Letrozole	Participants will receive letrozole, ribociclib and palazestrant-matching placebo

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 3.5 years)	To compare PFS, based on a local investigator assessment, between investigational (palazestrant with ribociclib + letrozole-matching placebo) and control (letrozole with ribociclib + palazestrant-matching placebo) arms.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 3.5 years)	To evaluate PFS based on Blinded Independent Review Committee (BIRC) assessment
Overall Survival (OS)	From Date of Randomization until Death Due to Any Cause (estimated as up to 5.5 years)	To compare OS between investigational and control arms.
Overall response Rate (ORR)	From Date of Randomization until Tumor Response (estimated as up to 3.5 years)	To evaluate ORR based on local investigator assessment
Clinical Benefit Rate (CBR)	Proportion of subjects achieving CR, PR or SD with duration of at least 24 weeks (estimated as up to 3.5 years)	To evaluate CBR based on local investigator assessment
Safety and tolerability	Up to 42 days after end of treatment (estimated as up to 3.5 years)	To evaluate safety and tolerability assessed by AEs, SAEs, dose modifications, clinical laboratory parameters, ECGs, performance status and vital sign measurements
Pharmacokinetics (PK) of palazestrant and ribociclib	Every 28 days (estimated as up to 3.5 years)	To evaluate plasma levels of palazestrant and ribociclib to establish pharmacokinetic (PK) parameters
Health-related patient-reported outcomes (PROs)	Every 28 days (estimated as up to 3.5 years)	To evaluate the change from baseline in health-related PROs assessed using standardized instruments that are widely used in (breast) cancer clinical trials
Duration of Response (DOR)	From Date of Tumor Response (CR or PR) until Disease Progression (estimated as up to 3.5 years)	To evaluate DOR based on local investigator assessment

Trial Locations

Locations (1)

Clinical Trial Site; 🇦🇺 Nedlands, Western Australia, Australia