Olema Oncology Advances Pivotal Phase 3 Trials for Palazestrant in Metastatic Breast Cancer
Key Insights
Olema Oncology is progressing its pivotal Phase 3 OPERA-01 trial of palazestrant monotherapy in second/third-line metastatic breast cancer (search), with top-line data anticipated in 2026.
The company is preparing to initiate the Phase 3 OPERA-02 trial of palazestrant in combination with ribociclib for frontline metastatic breast cancer (search) in 2025, supported by promising efficacy data showing 13.8 months median progression-free survival.
With $392.7 million in cash reserves as of Q1 2025, Olema is well-positioned to advance its clinical pipeline, including the ongoing Phase 1 trial of KAT6 (search) inhibitor OP-3136 for multiple solid tumor applications.
Olema Pharmaceuticals reported continued progress in its clinical development programs during the first quarter of 2025, with significant advancements in its lead candidate palazestrant for estrogen receptor (search)-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (search).
Palazestrant Shows Promise in Combination Therapy
Updated data from Olema's ongoing Phase 1b/2 study of palazestrant in combination with the CDK4/6 (search) inhibitor ribociclib demonstrated encouraging efficacy in patients with ER+/HER2- advanced or metastatic breast cancer (search). As of February 18, 2025, the median progression-free survival (mPFS) reached 13.8 months among all patients treated with 120 mg of palazestrant and 600 mg of ribociclib daily (n=56). Notably, patients previously treated with a CDK4/6 inhibitor plus endocrine therapy (n=40) achieved a mPFS of 13.1 months.
These promising results support Olema's plans to initiate OPERA-02, a pivotal Phase 3 trial evaluating palazestrant in combination with ribociclib in frontline metastatic breast cancer (search) later this year. The trial is enabled by a collaboration with Novartis and a $250 million equity private placement completed in late 2024.
"Our focus remains on our pivotal palazestrant program, laying the foundation to successfully initiate OPERA-02 in frontline metastatic breast cancer (search), while advancing OPERA-01 towards an anticipated top-line readout next year," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology.
OPERA-01 Trial Advances Toward Key Readout
The company continues to advance its pivotal Phase 3 OPERA-01 trial evaluating palazestrant as a monotherapy in second- and third-line ER+/HER2- metastatic breast cancer (search). This trial is investigating palazestrant in patients whose disease has progressed following endocrine therapy and CDK4/6 (search) inhibitor treatment. Top-line data from OPERA-01 are anticipated in 2026.
A trial-in-progress poster titled "OPERA-01: A randomized, open-label, phase 3 study of palazestrant (OP-1250) monotherapy vs standard-of-care endocrine therapy for patients with ER+, HER2- advanced breast cancer (search) after endocrine and CDK4/6 (search) inhibitor therapy" will be presented at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting in June.
Expanding Pipeline with OP-3136
Beyond palazestrant, Olema is advancing OP-3136, a potent lysine acetyltransferase 6 (KAT6 (search)) inhibitor. The company presented new preclinical data for OP-3136 at the American Association for Cancer Research (AACR) Annual Meeting in April, demonstrating anti-tumor activity in pre-clinical in vitro and in vivo ovarian, non-small cell lung, and prostate cancer (search) models, regardless of KAT6A expression status. The data also showed synergy with standard of care drugs.
"We were pleased to present promising new preclinical data at AACR supporting the use of OP-3136, our potent KAT6 (search) inhibitor, in a number of solid tumor applications beyond breast cancer (search)," noted Dr. Bohen. "Investigator interest in our OP-3136 program remains strong and we are continuing to enroll patients in the Phase 1 study."
The Phase 1 study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of OP-3136 in participants with advanced solid tumors is currently enrolling patients, following FDA clearance of the Investigational New Drug (IND) application in December 2024.
Financial Position
Olema reported a strong financial position with $392.7 million in cash, cash equivalents, and marketable securities as of March 31, 2025. The company reported a net loss of $30.4 million for the first quarter of 2025, compared to $31.0 million for the same period in 2024.
Research and development expenses were $30.6 million for the quarter, reflecting increased spending on clinical operations and development activities for palazestrant's late-stage clinical trials and the advancement of OP-3136. General and administrative expenses were $4.2 million for the quarter.
"With a clear strategy and strong balance sheet to support execution against our key priorities, we are working diligently to advance the promise of Olema's science and striving to change the treatment paradigm for endocrine-driven cancers," said Dr. Bohen.
About Palazestrant and OP-3136
Palazestrant (OP-1250) is a novel, orally available small molecule with dual activity as both a complete estrogen receptor (search) (ER) antagonist (CERAN) and selective ER degrader (SERD). In clinical studies, it has demonstrated complete blockade of ER-driven transcriptional activity in both wild-type and mutant forms of metastatic ER+ breast cancer (search), with favorable pharmacokinetics, tolerability, central nervous system penetration, and combinability with CDK4/6 (search) inhibitors. The FDA has granted Fast Track designation to palazestrant for the treatment of ER+/HER2- metastatic breast cancer that has progressed following endocrine therapy with at least one line given in combination with a CDK4/6 inhibitor.
OP-3136 is a novel, orally available small molecule that selectively inhibits lysine acetyltransferase 6 (KAT6 (search)), an epigenetic target dysregulated in breast and other cancers. Preclinical studies have shown significant anti-proliferative activity in ER+ breast cancer (search) models and synergy with endocrine therapies including palazestrant and CDK4/6 (search) inhibitors.
Olema Oncology is headquartered in San Francisco with operations in Cambridge, Massachusetts, and is focused on developing targeted therapies for breast cancer (search) and beyond.