Palazestrant

Shows activity

Also known as:

OP-1250

Cancer types include:

breast cancer

TrialFetch AI Analysis

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Overview

Palazestrant (OP-1250) is an investigational oral treatment for estrogen receptor–positive, HER2-negative advanced or metastatic breast cancer. Human results are available from an open-label phase 1/2 monotherapy study and an early-phase study combining it with ribociclib. The reported efficacy results are not yet a comparison against standard treatment. (link.springer.com)

Mechanism of action

Palazestrant targets the estrogen receptor. It is designed to block both of the receptor’s transcriptional activation domains (AF1 and AF2) and promote receptor degradation. Preclinical studies found activity against receptors with and without ESR1 mutations; whether that translates into a clinical advantage remains to be established. (link.springer.com)

Efficacy

In the published phase 1/2 monotherapy study, 146 patients enrolled. At the 120-mg daily dose, 3 of 66 patients with measurable disease (4.5%) had a confirmed partial response by the study’s data cutoff. The clinical benefit rate was 45.7%, and median progression-free survival was 4.8 months; among patients whose cancers had ESR1 mutations, median progression-free survival was 5.6 months. (link.springer.com)

A 2025 conference poster reported preliminary results for palazestrant plus ribociclib: 15 of 44 response-evaluable patients (34%) had a confirmed complete or partial response. The population included patients both with and without prior CDK4/6-inhibitor treatment, so this rate should not be compared directly with the monotherapy result. (ir.olema.com)

Safety

At 120 mg daily in the monotherapy study, the most common treatment-emergent adverse events were nausea (62.8%), vomiting (29.1%), and fatigue (25.6%); most events were grade 1 or 2. Treatment-related grade 4 neutropenia occurred in 5 of 86 patients (5.8%). In the combination study, neutropenia was also common, but its contribution from each drug cannot be determined from the single-arm results. (link.springer.com)

Active trials using Palazestrant

Found 3 active trials using this drug:

A Phase 3 Randomized, Double-Blind, Active-Controlled Study of Palazestrant With Ribociclib Versus Letrozole With Ribociclib for the First-Line Treatment of ER+, HER2- Advanced Breast Cancer (OPERA-02)

Sponsor: Olema Pharmaceuticals, Inc. (industry) Phase: 3 Start date: Nov. 3, 2025

TrialFetch AI summary: Adults with ER-positive, HER2-negative locally advanced or metastatic breast cancer who have received no systemic therapy for advanced disease are randomized to first-line palazestrant plus ribociclib or letrozole plus ribociclib. Palazestrant is an oral estrogen receptor–targeting agent designed to inhibit AF1 and AF2 transcriptional activity and promote receptor degradation.

ClinicalTrials.gov ID: NCT07085767

A Phase 3 Randomized, Open-Label Study of OP-1250 Monotherapy vs Standard of Care for the Treatment of ER+, HER2- Advanced or Metastatic Breast Cancer Following Endocrine and CDK 4/6 Inhibitor Therapy (OPERA-01)

Sponsor: Olema Pharmaceuticals, Inc. (industry) Phase: 3 Start date: Nov. 16, 2023

TrialFetch AI summary: Adults with ER-positive, HER2-negative advanced or metastatic breast cancer that has progressed after endocrine therapy plus a CDK4/6 inhibitor, with no prior chemotherapy for advanced disease, are randomized to oral palazestrant or investigator’s choice of fulvestrant or an aromatase inhibitor. Palazestrant targets the estrogen receptor by inhibiting AF1/AF2 transcriptional activation and promoting receptor degradation.

ClinicalTrials.gov ID: NCT06016738

A Phase 1b Open-Label Multicenter Study of OP-1250 (Palazestrant) in Combination With the CDK4/6 Inhibitor Ribociclib, With the PI3K Inhibitor Alpelisib, or With the mTOR Inhibitor Everolimus in Adult Subjects With Advanced and/or Metastatic ER Positive, HER2 Negative Breast Cancer

Sponsor: Olema Pharmaceuticals, Inc. (industry) Phase: 1 Start date: Aug. 31, 2022

TrialFetch AI summary: Adults with ER-positive, HER2-negative advanced or metastatic breast cancer and ECOG performance status 0–1 receive investigational palazestrant, an estrogen receptor antagonist that also promotes receptor degradation, combined with ribociclib (CDK4/6 inhibitor), alpelisib (PI3K inhibitor), or everolimus (mTOR inhibitor). Prior hormonal therapy is limited to one regimen for the ribociclib group and two for the alpelisib and everolimus groups.

ClinicalTrials.gov ID: NCT05508906