Olema Oncology has announced a new clinical trial collaboration and supply agreement with Pfizer to evaluate the combination of palazestrant and atirmociclib in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) metastatic breast cancer. The Phase 1b/2 study will explore the safety and combinability of these two investigational agents in approximately 35 patients, with initiation anticipated in the second half of 2025.
Novel Combination Approach
The study will combine palazestrant, Olema's proprietary complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD), with atirmociclib, Pfizer's investigational highly selective CDK4 inhibitor. According to Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology, "We are excited to assess this combination in the clinic as we seek to establish palazestrant as a potential backbone endocrine therapy for metastatic breast cancer."
The collaboration aims to leverage the promising profiles of both compounds demonstrated to date. Bohen noted that if successful, the companies plan to advance to a pivotal trial in the frontline setting, stating, "Based on the promising profiles of palazestrant and atirmociclib to date, we look forward to evaluating the potential of this novel combination and, if successful, advancing to a pivotal trial in the frontline setting."
Study Structure and Ownership
Under the terms of the agreement, Pfizer will supply atirmociclib for use in the Phase 1b/2 study while Olema will lead the conduct of the study. All clinical data and inventions relating to the combined use of atirmociclib and palazestrant resulting from the study will be jointly owned, with Olema maintaining full global commercial and marketing rights to palazestrant.
The results from this combination study are expected to inform a potential pivotal Phase 3 trial of the novel combination in the frontline metastatic breast cancer setting, representing a significant step forward in treatment development for this patient population.
Expanding Partnership
This announcement represents Olema's second clinical trial agreement with Pfizer. The companies' previous agreement was established in November 2020 to evaluate palazestrant in combination with palbociclib (IBRANCE®) in patients with recurrent, locally advanced or metastatic ER+/HER2- breast cancer.
Palazestrant Development Program
Palazestrant (OP-1250) is currently being investigated as a novel, orally available small molecule with dual activity as both a complete estrogen receptor (ER) antagonist (CERAN) and selective ER 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) inhibitors.
The compound has been granted U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of ER+/HER2- metastatic breast cancer that has progressed following one or more lines of endocrine therapy with at least one line given in combination with a CDK4/6 inhibitor.
Broader Clinical Development Strategy
Palazestrant is currently being evaluated as a single agent in the ongoing pivotal Phase 3 clinical trial, OPERA-01, and is anticipated to be evaluated in combination with ribociclib in the planned pivotal Phase 3 clinical trial, OPERA-02. Bohen emphasized the company's comprehensive approach, stating, "With OPERA-01, our first pivotal study of palazestrant, underway and our OPERA-02 ribociclib combination trial in frontline metastatic breast cancer anticipated to initiate this quarter, we remain focused on achieving our goal of transforming the metastatic breast cancer treatment paradigm."
The compound has also been evaluated in multiple Phase 1/2 studies in combination with ribociclib, palbociclib, alpelisib, and everolimus, demonstrating its potential for combination therapy approaches across different treatment settings.
