ER Y537C

The APIS ESR1 Mutations Kit demonstrated high sensitivity and specificity as a qualitative qPCR assay for detecting ESR1 mutations in varying WT backgrounds. Its performance with the SensID ESR1 Reference Set 1% AF cfDNA validated the kit's LoD at ≤1% MAF with external samples. The APIS kit is a valuable tool for assessing ESR1 mutations in both clinical and research settings, offering a more accessible alternative to traditional next-generation sequencing (NGS) and dPCR assays.

P3, N=400, Not yet recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

The developed novel multi-marker liquid bead array assay for the simultaneous detection of PIK3CA and ESR1 hotspot mutations in single CTCs is highly specific, highly sensitive, high-throughput, and sample-, cost-, and time-saving. This multi-marker liquid bead array assay can be extended to detect up to 100 mutations in many genes at once and can be applied for bulk CTC and ctDNA analysis.

This analysis identified acquired gene alterations in patients with HR+/HER2- advanced breast cancer treated with ribociclib plus ET or placebo plus ET. These data may support further studies on acquired resistance mechanisms and inform future systemic interventions in the post-CDK4/6 inhibitor setting.

P2, N=100, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Feb 2024 --> Dec 2024 | Trial primary completion date: Feb 2024 --> Dec 2024

P2, N=29, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Jan 2024 --> May 2024 | Trial primary completion date: Jan 2024 --> May 2024

These include proteins involved in highly dynamic processes such as sumoylation and ubiquitination difficult to detect with traditional protein interaction approaches. Overall, we present BAR as an effective approach to investigate the ERα proximal proteome in a spatial context and demonstrate its application in different experimental conditions.

P2, N=29, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Feb 2023 --> Jan 2024 | Trial primary completion date: Feb 2023 --> Jan 2024

Several oral ERa degraders were active against compound mutant models. We have identified a resistance mechanism specific to fulvestrant, that can be targeted by treatments in clinical development.

ESR1 mutations do not seem to be involved in the mechanisms of resistance to AI or M in HR+ endometrial cancer. The clinical relevance of their detection is not demonstrated.

The ESR1 Mutations Kit demonstrated high sensitivity and performance as a qualitative qPCR assay to detect eleven ESR1 mutations. Mutations detected with the APIS ESR1 Mutations Kit

The APIS ESR1 Mutations Kit demonstrated high sensitivity and performance as a qualitative qPCR assay to detect 11 ESR1 mutations.

Our assays have proven to be robust and highly sensitive and are very well-suited for monitoring ESR1 mutations in the plasma of MBC patients.

P2, N=100, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Feb 2023 --> Feb 2024 | Trial primary completion date: Feb 2023 --> Feb 2024

P2, N=29, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Nov 2022 --> Feb 2023 | Trial primary completion date: Nov 2022 --> Feb 2023

Differential gene expression analysis demonstrates up-regulation of estrogen-responsive genes, as expected, but also reveals that enrichment for interferon-regulated gene expression is a common feature of all mutations. Finally, a new gene signature developed from the gene expression profiles in ER mutant cells predicts clinical response in breast cancer patients with ER mutations.

P2, N=100, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Feb 2022 --> Feb 2023 | Trial primary completion date: Feb 2022 --> Feb 2023

The aim of this study was to explore the incidence of circulating ESR1 mutations in patients treated by AA or megestrol acetate (M) for advanced endometrial carcinoma.Methodology: This single-center retrospective study was performed at the Henri Becquerel Center (Rouen) and looked for circulating ESR1 gene mutations by droplet digital PCR (E380Q, L536R, Y537S, Y537N, Y537C, D538G, S463P) in patients with advanced HR+ endometrial carcinoma treated between 2008 and 2020 for at least 30 days by AA or M. Timepoints were before exposure and at progression/during endocrine therapy. 22 patients were included: 13 were treated with AA, 12 of whom progressed; 9 patients were treated with M, 8 of whom progressed... ESR1 mutations do not seem to be involved in the mechanisms of resistance to AA or M in HR+ endometrial cancer. The clinical relevance of their detection is not demonstrated.

P2, N=29, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial primary completion date: May 2022 --> Nov 2022

We have identified a novel resistance mechanism to fulvestrant, with F404 mutations acquired in patients with pre-existing activating ESR1 mutations. F404 confers fulvestrant resistance through the loss of a pi-stacking bond and likely reduced fulvestrant binding affinity, identifying a new potential target to overcome endocrine therapy resistance.

We present a low cost, highly specific, sensitive and robust assay for blood-based ESR1 profiling. The developed assay is fast, with a comparable sensitivity to ddPCR but has lower cost relative to ddPCR, and thus can be used as a fast screening method to classify patients as positive or negative for ESR1 mutations. Our results are consistent with reports that indicate that ESR1 mutations (especially D538G, Y537S) are associated with more aggressive disease.

P2, N=100, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Recruiting --> Active, not recruiting

P2, N=29, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Recruiting --> Active, not recruiting

The total concordance rate between ESR1 status on tumor tissue and plasma was 91%. Our results confirm the potential role of liquid biopsy as a non-invasive alternative to tissue biopsy for ESR1 mutation assessment in mBC patients.

We present a low cost, highly specific, sensitive and robust assay for blood-based ESR1 profiling. The clinical performance of the ESR1 NAPA assay will be prospectively evaluated in a large number of well-characterized patient cohorts.

P2, N=100, Recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Sep 2020 --> Feb 2022 | Trial primary completion date: Jul 2020 --> Feb 2022

Furthermore, the monitoring of circulating tumor DNA using this technique during treatment follow-up predicts the clinical benefit of palbociclib-fulvestrant. The multiplex ESR1-ddPCR detects, in a single reaction, the most frequent ESR1 activating mutations with good sensitivity. This method allows real-time liquid biopsy for ESR1 mutation monitoring in large cohorts of patients.

P2, N=24, Recruiting, Sermonix Pharmaceuticals Inc. | Not yet recruiting --> Recruiting | Initiation date: Jul 2020 --> Sep 2020

ER mutations are detectable in plasma from patients with advanced prostate cancer. ER splice variants are frequently detected in both men with and without prostate cancer.

P2, N=24, Not yet recruiting, Sermonix Pharmaceuticals Inc.

Comparable F-FES uptake between Y537S-, Y537C-, and WT-ER xenografts was also observed using a 10-fold lower injected dose with the tissue biodistribution assay. Since tumoral uptake of F-FES is not significantly impacted by Y537S or Y537C ER mutations, the potential diagnostic utility of F-FES PET imaging is expected to be equally valid for patients with or without these activating ESR1 mutations.