On May 31, 2022 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat ESR1-mutated metastatic breast and gynecological cancers, reported two abstracts accepted for presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is being held June 3-7 at McCormick Place in Chicago, and online (Press release, Sermonix Pharmaceuticals, MAY 31, 2022, View Source [SID1234615328]).

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"We are very pleased to be able to present compelling data from our ELAINE-2 study at this year’s ASCO (Free ASCO Whitepaper) meeting," stated Dr. David Portman, founder and chief executive officer of Sermonix. "It has been well established that the development of ESR1 mutations is strongly associated with increasing resistance to aromatase inhibitor (AI) therapies, disease progression and poor long-term outcomes. Our ELAINE-2 study is evaluating investigational lasofoxifene in combination with the CDK4/6 inhibitor abemaciclib for the treatment of metastatic breast cancer with an ESR1 mutation. Lasofoxifene plus abemaciclib met the primary and secondary study endpoints in these women who had progressed on previous CDK4/6i therapies. We are encouraged by the results to date from this study and are excited to move forward with our clinical development program for lasofoxifene. ELAINE-2 is the first study to show positive efficacy results with a selective estrogen receptor modulator (SERM) and CDK4/6 in this challenging post-CDK4/6 treated population.

"Based on these data, we believe lasofoxifene, as the only SERM currently being developed exclusively to treat breast cancers with ESR1 mutations, has the potential, if approved, to play a critical role in the targeted precision medicine treatment of advanced ER+ breast cancer. Because of our belief that lasofoxifene can be an endocrine backbone of choice, we are planning to study it in combination with other therapies in mBC patients who have an ESR1 mutation.

"In parallel, our ELAINE-1 study, which is assessing lasofoxifene as monotherapy compared to fulvestrant for the treatment of metastatic breast cancer with an ESR1 mutation post-CDK4/6i therapy, is fully enrolled, and we will be presenting data in late Q3 of this year," Dr. Portman concluded.

Details of the presentations are as follows:

Title: Open-label, Phase 2, Multicenter Study of Lasofoxifene (LAS) Combined with Abemaciclib (Abema) for Treating Pre- and Post-Menopausal Women with Locally Advanced or Metastatic ER+/HER2− Breast Cancer and an ESR1 Mutation after Progression on Prior Therapies

Abstract number: 1022

Session type: Poster Discussion

Session: Breast Cancer – Metastatic

Date: Monday, June 6, 2022

Time: 9 a.m.-12 p.m. EDT

From the summary, resistance to endocrine therapy can develop when treating estrogen receptor positive (ER+), metastatic breast cancer (mBC). Treatment with aromatase inhibitors can lead to acquired mutations in the estrogen receptor 1 (ESR1), which can constitutively activate the ER, leading to endocrine resistance, metastases and worse disease prognosis. Treatment options for mBC patients with an ESR1 mutation are limited. Further, retrospective data suggest that patients could derive clinical benefit from Abema after progression on prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i).1

ELAINE-2 is an open-label, phase 2, multicenter trial evaluating the safety and efficacy of LAS combined with the CDK4/6i, Abema. Study participants were pre- and postmenopausal women with ER+/HER2- mBC with acquired ESR1 mutation (identified by ctDNA testing), whose disease had progressed on one or two lines of hormonal therapy for metastatic disease with or without a CDK4/6i (including Abema). Abema (Verzenio) was provided through a drug supply collaboration with Eli Lilly and Co. Treatment continued until evidence of disease progression, death, unacceptable toxicity or withdrawal from the study. The primary endpoint was safety, and secondary endpoints were progression free survival (PFS), objective response rate (ORR) and clinical benefit rate (CBR).

Results: 29 patients were enrolled, and most had progressed with at least two previous hormonal treatments (80%). All except one patient received a prior CDK4/6i and 72% had received prior fulvestrant; 48% had chemotherapy in the metastatic setting. To date, 11 patients have progressed and 14 continue treatment. Median PFS was 13.9 months, ORR was 33.3% and CBR was 62.1% at the time of analysis.

Title: Operational Metrics for the ELAINE II Study Combining a Traditional Approach with a Just-in-Time Model2

Abstract number: 1504

Session type: Oral Abstract

Session: Care Delivery and Regulatory Policy

Date: Monday, June 6, 2022

Time: 4 -7 p.m. EDT

Trial recruitment that requires specific actionable mutations based on next-generation sequencing (NGS) is challenging. Barriers can include competing studies, physician study awareness, site proximity, mutation incidence, among other concerns.

This study opened clinical sites using two methods during the COVID-19 pandemic. The "Traditional" approach included site selection, IRB and contract approval, and trial activation prior to a patient being identified for enrollment. The second approach used the Tempus "TIME" Trials network that would only open a site after identifying a patient with a mutation of interest and eligibility for the trial.

A total of 16 sites (6 Traditional and 10 TIME) participated. All Traditional sites, and none of the TIME sites, were affiliated with major academic institutions. Duration for full CTA execution for Traditional sites averaged 200.5 days (range 142 to 257) and for TIME sites averaged 7.6 days (range 2 to 14). IRB approval time average for Traditional sites was 27.5 days (range 12 to 71) and TIME sites was 3.0 days (range 1 to 12 days). Days from site selection to activation letter for Traditional sites was on average 250.0 days (range 187 to 281) and for TIME sites was 131.6 days (range 22 to 248). Time from study activation to first consent was 33.3 days (range 18 to 58) for Traditional sites and 8.8 days (range 1 to 35) for TIME sites. The first patient on-study was at a TIME site 115 days prior to a Traditional site and the first 7 patients enrolled were at TIME sites. Traditional sites consented 23 and enrolled 16 patients while the TIME sites consented 16 and enrolled 13. The trial enrolled all 29 patients in 8 months with the anticipated enrollment duration being 12 to 18 months.

1 Wander SA et al. J Natl Compr Canc Netw, doi: 10.6004/jnccn.2020.7662. Published online 3/24/22

Conclusion: Although the Traditional and TIME programs had different operational models, they both contributed a significant number of patients and reduced the projected enrollment timeline. TIME sites enrolled the initial patients. These results demonstrate that the "Just-in-Time model," in conjunction with a Traditional model, can reduce projected overall time to enrollment in biomarker-driven studies.

2 Abstract submitted by, and will be presented by, Tempus, a leader in artificial intelligence and precision medicine.

About Lasofoxifene

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.