Sermonix Pharmaceuticals and Quantum Leap Healthcare Collaborative announced positive results from a Phase 2 clinical trial evaluating lasofoxifene as a neoadjuvant endocrine therapy for HR+/HER2- locally advanced breast cancer. The investigational drug was well-tolerated and demonstrated promising early activity in suppressing the Ki67 protein, a marker of cancer cell division, in both premenopausal and postmenopausal patients.
The study, part of the Endocrine Optimization Pilot Protocol (EOP) within the I-SPY 2 TRIAL, enrolled 20 patients (10 premenopausal, 9 postmenopausal women, and 1 male). Results, initially shared at RISE UP for Breast Cancer, showed that median Ki67 expression decreased from 10% at baseline (range 1.0-40%) to 4% (1.0-18.0%) at Week 3. Notably, Ki67 expression was suppressed to <10% in 14 out of 16 (88%) patients and to <2.7% in 6 out of 16 (38%) patients at three weeks.
Ki67 Suppression and Tolerability
Dr. David Portman, founder and CEO of Sermonix, emphasized lasofoxifene's strong tolerability profile and promising Ki67 suppression, stating that these results support further exploration in the neoadjuvant setting. He also noted the ongoing ELAINE-3 Phase 3 combination study with abemaciclib in ESR1-mutated metastatic breast cancer, highlighting the drug's broad potential and quality of life benefits.
Impact on Premenopausal Women
An important observation was the early Ki67 suppression in premenopausal patients without ovarian function suppression (OFS). Dr. Jo Chien, principal investigator of the sub-study, noted that lasofoxifene demonstrated significant activity in both postmenopausal women and 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. She added that lasofoxifene was well-tolerated even in younger patients often impacted by the side effects of standard endocrine therapy.
Safety Profile
The median total treatment duration was 154 days, with three patients still on treatment at the time of data analysis. Adverse events (AEs) were primarily grade 1-2, with the most common being hot flushes (65%), constipation (40%), fatigue (40%), and nausea (25%).
Lasofoxifene: A Novel Endocrine Therapy
Lasofoxifene is an investigational endocrine therapy that has demonstrated robust target engagement as an ESR1 antagonist, 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. Its unique tissue selectivity, with beneficial effects on the vagina and bone, distinguishes it from other endocrine therapies. Sermonix licensed lasofoxifene globally from Ligand Pharmaceuticals Inc., and it has been studied in over 15,000 postmenopausal women in previous Phase 1-3 non-oncology clinical trials.
I-SPY 2 TRIAL Details
The I-SPY 2 TRIAL is designed to rapidly screen promising experimental treatments and identify those most effective in specific patient subgroups based on biomarker signatures. It is a collaborative effort involving the FDA, industry, patient advocates, philanthropic sponsors, and clinicians from major U.S. cancer research centers. Quantum Leap Healthcare Collaborative serves as the trial sponsor and manages all study operations.
