On June 5, 2023 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast cancers harboring ESR1 mutations, reported a poster presentation detailing the results of its ELAINE-2 clinical study with longer patient follow-up (Press release, Sermonix Pharmaceuticals, JUN 5, 2023, View Source [SID1234632524]). The poster was initially presented yesterday at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
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ELAINE-2 (NCT04432454), an open-label, Phase 2 Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE) study of Sermonix’s lead investigational drug, lasofoxifene, in combination with Eli Lilly and Company’s CDK4/6 inhibitor abemaciclib, evaluated 29 women with ER+/HER2- locally advanced or metastatic breast cancer and an ESR1 mutation. The primary endpoint was safety/tolerability, with secondary endpoints including progression-free survival (PFS) and overall response rate (ORR). Earlier ELAINE-2 results were shared at ASCO (Free ASCO Whitepaper) 2022.
With patient follow-up through Jan. 31, 2023, the combination of lasofoxifene and abemaciclib continued to be well-tolerated, with clinically meaningful efficacy in women with ER+/HER2- metastatic breast cancer and an ESR1 mutation. The PFS, a median of 13 months, and ORR of 56% were promising.
"No new safety signals were noted when looking at lasofoxifene and abemaciclib with longer patient follow-up," said Paul Plourde, M.D., vice president of oncology clinical development at Sermonix. "The combination demonstrated meaningful antitumor activity, and observed decreases in ESR1 ctDNA suggest potent target engagement. We look forward to ELAINE-3 and the continued investigation of this potentially practice-changing option for treating ESR1 mutations in women with metastatic breast cancer."
Noteworthy safety results:
Lasofoxifene/abemaciclib was well tolerated with primarily grade 1/2 treatment-emergent adverse events (TEAEs), most commonly diarrhea, nausea, fatigue, and vomiting.
Three patients (10.3%) had venous thromboembolic events, all occurring after patients had achieved clinical benefit.
One patient discontinued treatment due to grade 2 diarrhea, and no deaths on treatment occurred.
Abemaciclib underwent dose reduction once in 6 (20.7%) patients; there were no dose reductions for lasofoxifene.
There was no clinical evidence of any drug-drug interactions, and no pK impact of lasofoxifene on abemaciclib or abemaciclib on lasofoxifene exposure identified (data not shown).
Noteworthy efficacy results:
Median PFS was 56.0 wks (~13 mos), CBR was 65.5%, and ORR was 55.6%; median overall survival was not estimable at the time.
PFS rate (95% CI) was 76.1%, 56.1%, and 38.8% at 6, 12, and 18 mos respectively; 8 (27.6%) patients achieved PFS over 96 weeks.
Of the four patients who had prior abemaciclib exposure, two achieved clinical benefit, and one with RECIST progression at week 16 remained on study with stable disease until week 40.
In 26 patients with evaluable baseline and week 4 ctDNA, ESR1 mutant allele fractions (MAF) decreased at week 4 in 21 (80.8%) patients, including 14 (53.8%) whose ESR1 MAF were undetectable.
Antitumor activity of lasofoxifene/abemaciclib was not compromised by co-occurring alterations that confer endocrine resistance.
Sermonix in March initiated ELAINE-3, a registrational Phase 3 study of 400 patients assessing the efficacy of lasofoxifene and abemaciclib. Enrollment will begin soon.
The company also convened meetings of its ELAINE-3 Steering Committee and ELAINE-3 Translational Committee at ASCO (Free ASCO Whitepaper) 2023.
To learn more about Sermonix Pharmaceuticals and lasofoxifene, visit View Source To learn more about the ELAINE studies, visit View Source
About Lasofoxifene
Lasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with a CDK4/6 inhibitor in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies, with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ:LGND), 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 novel targeted and tissue selective oral endocrine therapy could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.