Sermonix Pharmaceuticals Announces Results of Phase 2 Study of Lasofoxifene vs. Fulvestrant in Postmenopausal Women With Locally Advanced or Metastatic ER+/HER2- Breast Cancer and an ESR1 Mutation
COLUMBUS, Ohio, Sept. 13, 2022 (GLOBE NEWSWIRE) -- Sermonix Pharmaceuticals LLC, a privately held biopharmaceutical company developing innovative therapeutics to specifically treat ESR1-mutated metastatic breast and gynecological cancers, today announced results of its signal-seeking Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE 1) Phase 2 study. The results were initially shared Sept. 10 during a late-breaking oral presentation at the European Society for Medical Oncology (ESMO) Congress 2022 in Paris.
The open-label ELAINE 1 (NCT03781063) study began U.S. enrollment in September 2019, assessing the efficacy and safety of oral lasofoxifene versus intramuscular fulvestrant, a selective estrogen receptor degrader (SERD), in 103 patients. All participants were post-CDK4/6 inhibitor/aromatase inhibitor therapy and had an ESR1 mutation. Progression-free survival was the primary endpoint.
Top-line data included:
- Median progression-free survival (PFS) was 6.04 mos. (95% CI, 2.82–8.04) for lasofoxifene vs. 4.04 mos. (95% CI, 2.93–6.04) for fulvestrant, P=0.138 (HR, 0.699 [95% CI, 0.445–1.125])
- Clinical benefit rate (CBR) was 36.5% for lasofoxifene vs. 21.6% for fulvestrant, P=0.12. CBR is defined as the percentage of all subjects with a complete or partial response; or stable disease for >/= 24 weeks
- Objective response rate was 13.2% for lasofoxifene vs. 2.9% for fulvestrant, P=0.12, with 1 confirmed complete response (CR) (72-week duration) and 4 confirmed partial responses (PR) in the lasofoxifene arm vs. 1 PR in the fulvestrant arm
- PFS was numerically and consistently greater with lasofoxifene vs. fulvestrant when visceral metastasis and/or Y537S ESR1 mutation subgroups were analyzed
- While not reaching statistical significance in this 103-patient study, all endpoints numerically favored lasofoxifene
Exploratory endpoints included:
- PFS at 6 mos. for lasofoxifene was 53.4% vs. 37.9% for fulvestrant; PFS at 12 mos. was 30.7% for lasofoxifene vs. 14.1% for fulvestrant
- Clearance of ctDNA also favored lasofoxifene over fulvestrant
- Most common adverse events were fatigue, nausea, arthralgias and hot flashes; most were Grade 1/2. No thrombotic events occurred
ELAINE 1 is the first clinical trial comparing lasofoxifene with fulvestrant in ESR1-mutated metastatic breast cancer patients with progression on an aromatase inhibitor (Al) in combination with a CDK4/6 inhibitor, and the first to demonstrate anti-tumor activity and target engagement of a novel selective estrogen receptor modulator (SERM) in this setting. ELAINE 2, a Phase 2 single-arm trial of lasofoxifene in combination with the CDK4/6 inhibitor abemaciclib, showed efficacy in heavily pretreated patients with ESR1-mutated mBC post-CDK4/6i (ASCO 2022).
“Sermonix is pleased with the outcomes reported in our ELAINE 1 trial comparing lasofoxifene with fulvestrant, suggesting lasofoxifene’s anti-tumor activity and potential to play a critical role in the targeted precision medicine treatment of ESR1-mutated advanced ER+ breast cancer,” said Dr. David Portman, Sermonix founder and chief executive officer. “Lasofoxifene following endocrine/CDK4/6 inhibitor therapies continues to be studied and we anticipate efficacy will be confirmed in a larger clinical study. Sermonix is planning a Phase 3 registrational combination study based on these results as well as encouraging efficacy and safety demonstrated in the ELAINE 2 study of lasofoxifene and abemaciclib reported at this year’s ASCO annual meeting.”
“ELAINE 1 suggested lasofoxifene's activity in patients with metastatic breast cancer post-CDK4/6i and an ESR1 mutation,” said Dr. Paul Plourde, Sermonix vice president for clinical oncology development. “While not reaching statistical significance in our modestly powered study, all efficacy parameters numerically favored lasofoxifene over fulvestrant. Moreover, the safety profile indicates lasofoxifene was well tolerated with few Grades 3 and 4 adverse events and a differentiated profile from injectable and oral SERDs. Lasofoxifene trials may offer new hope for patients with mutated ESR1 metastatic breast cancer.”
Lasofoxifene is an investigational, nonsteroidal selective estrogen receptor modulator (SERM), which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ: LGND) and has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a potent, oral SERM could, if approved, play a critical role in the targeted precision medicine treatment of advanced ER+ breast cancer.
Sermonix Pharmaceuticals Inc. is a privately held biopharmaceutical company focused on the development of female-specific oncology products and is currently undertaking two Phase 2 clinical studies of lasofoxifene, its lead investigational drug. Sermonix Pharmaceuticals was founded in 2014 by David Portman, M.D., a leading clinical researcher and expert in women’s health, menopause and selective estrogen receptor modulator (SERM) therapy. The Sermonix management team, led by Dr. Portman, has significant experience in all stages of the drug development and regulatory process. Paul Plourde, M.D., vice president of oncology clinical development, has many decades of experience in the oncology drug development arena. Barry Komm, Ph.D., chief scientific officer, is recognized for his expertise in SERM biology. Miriam Portman, M.D., is chief operating officer. Elizabeth Attias, M.M.Sc., Sc.D., chief strategy and development officer, has extensive experience in pharmaceutical drug commercialization. Simon Jenkins, Ph.D., vice president of operations, has over 30 years of experience in global drug development leadership. Sermonix non-executive chairman of the board is Anthony Wild, Ph.D., former president of both Parke-Davis Pharmaceuticals and Warner-Lambert’s Pharmaceutical Division. Learn more at SermonixPharma.com.
Managing Director, Investor Relations Corporate Communications