Palazestrant in Combination With Ribociclib for the First... | NCT07085767

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

NCT07085767

Sponsor

Olema Pharmaceuticals, Inc.

Status

Recruiting

Last Update Posted

Jun 16, 2026Actual

Enrollment

1,000Estimated

Phase

Phase 3

Conditions

Breast Cancer
Locally Advanced Breast Cancer
Metastatic Breast Cancer
ER Positive Breast Cancer
HER2 Negative Breast Carcinoma

Interventions

Palazestrant
Letrozole-matching placebo
Ribociclib
Letrozole
Palazestrant matching-placebo

Countries

United States
Australia
Austria
Belgium
Canada
Czechia
France
Germany
Greece
Hong Kong
Hungary
Italy
Malaysia
Netherlands
Poland
Portugal
Romania
South Korea
Spain
Taiwan
Thailand
United Kingdom

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

ID	Type	Description	Link
OPERA-02	Other Identifier	Olema Pharmaceuticals, Inc.

Status Module

Record Verification Date

Jun 2026

Overall Recruitment Status or Expanded Access Status

Recruiting

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Nov 3, 2025Actual

Primary Completion Date

Dec 2028Estimated

Completion Date

Jan 2032Estimated

First Submitted Date

Jul 8, 2025

First Submission Date that Met QC Criteria

Jul 18, 2025

First Posted Date

Jul 25, 2025Actual

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Jun 12, 2026

Last Update Posted Date

Jun 16, 2026Actual

Name	Class
Novartis Pharmaceuticals	INDUSTRY

Oversight Module

Has Data Monitoring Committee (DMC)

Yes

Is FDA Regulated Drug

Yes

Is FDA Regulated Device

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

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.

Conditions Module

Conditions

Breast Cancer
Locally Advanced Breast Cancer
Metastatic Breast Cancer
ER Positive Breast Cancer
HER2 Negative Breast Carcinoma

Keywords

Randomized
Multicenter
Double-Blind
Active-Controlled
Phase 3
Palazestrant
Complete Estrogen Receptor Antagonist (CERAN)
Selective Estrogen Receptor Degrader (SERD)
Ribociclib
CDK4/6i
Letrozole
Aromatase inhibitors
Antineoplastic agents

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 3

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

1,000Estimated

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Palazestrant	Experimental	Participants will receive palazestrant, ribociclib and letrozole-matching placebo	Drug: Palazestrant Drug: Letrozole-matching placebo Drug: Ribociclib
Letrozole	Active Comparator	Participants will receive letrozole, ribociclib and palazestrant-matching placebo	Drug: Ribociclib Drug: Letrozole Drug: Palazestrant matching-placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Palazestrant	Drug	Participants will be treated with palazestrant 90 mg once daily on a 4-week (28-day) cycle.	Palazestrant

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-Free Survival (PFS)	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.	From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 3.5 years)

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	To compare OS between investigational and control arms.	From Date of Randomization until Death Due to Any Cause (estimated as up to 5.5 years)
Progression Free Survival (PFS)

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

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.

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Name	Role	Phone	Extension	Email
Olema Pharmaceuticals, Inc.	Contact	415-651-7206		OPERA-02@olema.com

Overall Officials

Name	Affiliation	Role
Medical Director, MD	Olema Pharmaceuticals, Inc.	Study Director

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Trial Site	Active, not recruiting	Hot Springs	Arkansas	71913	United States

Label	URL
Olema Publications	View source

IPD Sharing Statement Module

Plan to Share IPD

Description

Not provided

Types

Not provided

Time Frame

Not provided

Access Criteria

Not provided

URL

Not provided

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D009570	Nitriles
D009930	Organic Chemicals
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds