Sermonix Pharmaceuticals and Quantum Leap Healthcare Collaborative announced positive results from the Phase 2 I-SPY 2 trial evaluating lasofoxifene as a neoadjuvant endocrine therapy for molecularly selected HR+/HER2- locally advanced breast cancer. The investigational drug was well-tolerated and demonstrated promising early activity in suppressing the Ki67 protein in both premenopausal and postmenopausal patients.
The findings, initially presented at RISE UP for Breast Cancer, stem from the Endocrine Optimization Pilot Protocol (EOP), a sub-study of the ongoing I-SPY 2 TRIAL. Twenty patients, including 10 pre- and 9 postmenopausal women, and one male, were enrolled in the lasofoxifene arm of the study between March 2023 and May 2024. The median total days of treatment was 154 days.
Ki67 Suppression
Early Ki67 suppression in premenopausal patients was observed even without ovarian function suppression (OFS). Ki67, a marker of cancer cell division, showed a median decrease from 10% at baseline (range 1.0-40%) to 4% (1.0-18.0%) at Week 3. By week three, Ki67 expression was suppressed to below 10% in 14 out of 16 (88%) patients, and to below 2.7% in 6 out of 16 (38%) patients.
Tolerability and Adverse Events
The adverse events reported were all grade 1-2. The most common adverse events included hot flushes (65%), constipation (40%), fatigue (40%), and nausea (25%).
Expert Commentary
Dr. David Portman, founder and CEO of Sermonix, stated, "Lasofoxifene continued to demonstrate a strong tolerability profile while showing promising Ki67 suppression in this Phase 2 study, supporting our plans to further explore its potential in the neoadjuvant setting." He also noted the ongoing ELAINE-3 Phase 3 combination study with abemaciclib in the ESR1-mutated metastatic breast cancer setting.
Dr. Jo Chien, principal investigator of the sub-study, added, "Lasofoxifene has demonstrated significant activity based on early Ki67 suppression, not only in postmenopausal women, but also in 10 premenopausal women without concomitant ovarian function suppression, with baseline Ki67 of 12.5% (1.0-40.0%) going to 3.0% (1.0-15%) at Week 3. It is exciting to see that lasofoxifene is well-tolerated even in our youngest patients who are often most impacted by the debilitating side effects of current standard endocrine therapy options."
About Lasofoxifene
Lasofoxifene is an investigational novel endocrine therapy that acts as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. It has shown anti-tumor activity as a monotherapy and in combination with a CDK4/6 inhibitor in Phase 2 studies. Sermonix licensed lasofoxifene globally from Ligand Pharmaceuticals Inc. It has been studied in previous Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide.
