FDA Aligns with Olema on 90mg Palazestrant Dose for Phase 3 Breast Cancer Trials
核心洞察
Olema Oncology has aligned with the FDA to select 90mg once-daily palazestrant as the dose for Part 2 of the Phase 3 OPERA-01 monotherapy trial in second- and third-line ER+/HER2- metastatic breast cancer (搜索).
The same 90mg dose will be used in combination with ribociclib for the pivotal Phase 3 OPERA-02 trial in frontline ER+/HER2- metastatic breast cancer (搜索).
Top-line data from OPERA-01 is anticipated in 2026 with a potential commercial launch in 2027, as the company advances its novel dual-mechanism estrogen receptor (搜索) antagonist and degrader.
Olema Oncology has reached alignment with the U.S. Food and Drug Administration (FDA) to select 90mg of palazestrant as the dose for Part 2 of the ongoing registrational Phase 3 OPERA-01 trial in second- and third-line estrogen receptor (搜索)-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) metastatic breast cancer (搜索). The FDA also selected the same 90mg dose of palazestrant in combination with the approved dose of CDK4/6 (搜索) inhibitor ribociclib for the pivotal Phase 3 OPERA-02 trial in frontline ER+/HER2- metastatic breast cancer.
The dose selection update will be presented as part of the OPERA-01 trial-in-progress poster at the American Society of Clinical Oncology (ASCO) Annual Meeting taking place May 30-June 3 in Chicago, Illinois.
Clinical Development Timeline and Commercial Prospects
"We remain steadfast in our commitment to these patients, and with 90mg of palazestrant confirmed as the selected dose, we are focused on rapidly advancing our OPERA-01 and OPERA-02 pivotal trials with top-line data from OPERA-01 anticipated in 2026 and a potential commercial launch in 2027," said Naseem Zojwalla, M.D., Chief Medical Officer of Olema Oncology.
The OPERA-01 trial is designed as a randomized, open-label, phase 3 study of palazestrant monotherapy versus standard-of-care endocrine therapy for patients with ER+, HER2- advanced breast cancer after endocrine and CDK4/6 (搜索) inhibitor therapy.
Addressing Treatment Resistance in Metastatic Breast Cancer
"Metastatic breast cancer (搜索) treatment continues to be challenged by resistance mechanisms resulting in a clear need for innovative new therapies. We believe the clinical results we have achieved to date for palazestrant across ESR1 (搜索) mutant and wild-type ER+/HER2- tumors, both in the monotherapy and combination treatment settings, support palazestrant's potential to have a significant positive impact on breast cancer patients," Zojwalla explained.
Novel Dual-Mechanism Drug Design
Palazestrant (OP-1250) is a novel, orally available small molecule with dual activity as both a complete estrogen receptor (搜索) antagonist (CERAN) and selective estrogen receptor degrader (SERD). In clinical studies, palazestrant completely blocks ER-driven transcriptional activity in both wild-type and mutant forms of metastatic ER+ breast cancer and has demonstrated anti-tumor efficacy along with attractive pharmacokinetics and exposure, favorable tolerability, central nervous system penetration, and combinability with cyclin-dependent kinase 4/6 (CDK4/6 (搜索)) inhibitors.
Regulatory Recognition and Broader Development Program
Palazestrant has been granted U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of ER+/HER2- metastatic breast cancer (搜索) that has progressed following one or more lines of endocrine therapy with at least one line given in combination with a CDK4/6 (搜索) inhibitor.
Beyond the pivotal Phase 3 trials, palazestrant is being evaluated in multiple Phase 1/2 trials in combination with ribociclib, palbociclib, alpelisib, and everolimus, demonstrating the drug's potential for combination therapy approaches across different treatment settings.
ASCO Presentation Details
The OPERA-01 trial-in-progress poster will be presented on Monday, June 2 between 9:00am–12:00pm CT / 10:00am–1:00pm ET as part of the Breast Cancer – Metastatic poster session. The presentation carries the abstract number TPS1131 and poster number 104b.