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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; All Endpoints Numerically Favored Lasofoxifene

COLUMBUS, Ohio, Sept. 13, 2022 (GLOBE NEWSWIRE) -- Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat ESR1-mutated metastatic breast and

Benzinga · 09/13/2022 09:15

COLUMBUS, Ohio, Sept. 13, 2022 (GLOBE NEWSWIRE) -- Sermonix Pharmaceuticals Inc., 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."