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

Phase 3

Active, not recruiting

• Conditions: Metastatic Breast Cancer; HER2 Negative Breast Carcinoma; Breast Cancer; Advanced Breast Cancer; ER Positive Breast Cancer
• Interventions: Drug: Fulvestrant; Drug: Palazestrant; Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane

• Registration Number: NCT06016738
• Lead Sponsor: Olema Pharmaceuticals, Inc.

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2023-08-17
• Study First Submitted QC: 2023-08-29
• Study First Posted: 2023-08-30
• Study Start: 2023-11-16
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-07
• Last Update Posted: 2025-03-11
• Primary Completion: 2026-06-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 510

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care Endocrine Therapy	Letrozole	Participants will receive Investigator's choice of one of the Standard of Care drugs (fulvestrant, anastrozole, letrozole, or exemestane)
Standard of Care Endocrine Therapy	Anastrozole	Participants will receive Investigator's choice of one of the Standard of Care drugs (fulvestrant, anastrozole, letrozole, or exemestane)
Standard of Care Endocrine Therapy	Fulvestrant	Participants will receive Investigator's choice of one of the Standard of Care drugs (fulvestrant, anastrozole, letrozole, or exemestane)
Palazestrant (OP-1250)	Palazestrant	Participants will receive Palazestrant
Standard of Care Endocrine Therapy	Exemestane	Participants will receive Investigator's choice of one of the Standard of Care drugs (fulvestrant, anastrozole, letrozole, or exemestane)

Primary Outcome Measures

Name	Time	Method
Dose-Selection Part: Incidence of dose reduction	From Date of Randomization up to 16 weeks	To evaluate the number of participants reducing the dose of palazestrant
Dose-Selection Part: Incidence of drug discontinuation	From Date of Randomization up to 16 weeks	To evaluate the number of participants discontinuing palazestrant
Trial: Progression-Free Survival (PFS)	From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 2 years)	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.
Dose-Selection Part: Incidence of adverse events	From Date of Randomization up to 16 weeks	To evaluate the number of participants with adverse events

Secondary Outcome Measures

Name	Time	Method
Trial: Overall Survival (OS)	From Date of Randomization until Death Due to Any Cause (estimated as up to 4 years)	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.

Trial Locations

Locations (2)

Clinical Trial Site; 🇬🇧 London, United Kingdom

Clinical Trials Site; 🇲🇾 Sungai Petani, Kedah, Malaysia