fulvestrant

P2, N=24, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Jan 2025 --> Jul 2025

P1, N=35, Completed, Vanderbilt-Ingram Cancer Center | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Mar 2024

P2, N=69, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2025 --> Aug 2025

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

P3, N=460, Not yet recruiting, Jiangsu Simcere Pharmaceutical Co., Ltd.

P1, N=20, Terminated, Hoffmann-La Roche | Phase classification: P3 --> P1

P2, N=52, Completed, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori | Unknown status --> Completed | N=150 --> 52

Dalpiciclib plus fulvestrant is effective and comparatively safe in postmenopausal women with hormone receptor-positive and HER2-negative breast cancers. Dalpiciclib, buparlisib, fulvestrant, and ribociclib cause neutropenia, severe depression, adverse gastroenterological effects, and adverse hepatological effects, respectively.

P2, N=15, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

Pharmacologic targeting of estrogen signaling (either by HSD17B7 inhibition or with fulvestrant) and chemokine inflammation both decrease local E2 and prevent macrophage polarization. Overall, these findings suggest that chronic inflammation and hormonal disposition are critical contributors to the age-related nature of ER+ breast cancer development and growth and offer potential therapeutic insight to treat these patients. We uncover the unique underpinnings establishing how the systemic host environment contributes to the aged breast tumor microenvironment, characterized by high local estradiol and chronic inflammation with immune dysregulation, and show that targeting avenues of estrogen conversion and chronic inflammation work to restore anti-tumor immunity.

Camizestrant at 75 and 150 mg showed a significant benefit in progression-free survival versus fulvestrant. These results support further development of camizestrant for the treatment of oestrogen receptor-positive, HER2-negative breast cancer.

P2, N=120, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

In patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer, inavolisib plus palbociclib-fulvestrant led to significantly longer progression-free survival than placebo plus palbociclib-fulvestrant, with a greater incidence of toxic effects. The percentage of patients who discontinued any trial agent because of adverse events was low. (Funded by F. Hoffmann-La Roche; INAVO120 ClinicalTrials.gov number, NCT04191499.).

P2, N=47, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting

P2, N=44, Recruiting, Marina N Sharifi | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

Fulvestrant (FUL), a selective estrogen receptor degrader used to treat AI-resistant ERα-positive postmenopausal BC, was found to induce degradation of ERα together with a decrease in ER-mediated transcription; however, FA2H protein expression and migration remained unchanged. Overall, the findings of this study suggest that FA2H is one of the drivers of LTED cell migration, and that LTED cells resistant to FUL therapy may be involved in malignancy and metastatic mechanisms.

P1, N=25, Not yet recruiting, University of Chicago

P1, N=54, Active, not recruiting, Abramson Cancer Center at Penn Medicine | Phase classification: P1/2 --> P1 | Trial completion date: Apr 2024 --> Dec 2024 | Trial primary completion date: Apr 2024 --> Dec 2024

P2, N=200, Recruiting, Oana Danciu | Active, not recruiting --> Recruiting

Imlunestrant, as monotherapy and combined with abemaciclib, has a manageable safety profile with preliminary evidence of antitumor activity in patients with ER+ EEC.

Estrogen receptor one (ESR1) gene mutations, driving resistance to aromatase inhibitors (AIs), may guide the use of fulvestrant or emerging oral selective estrogen receptor degraders (SERDs) like elacestrant. Targeting mutations like breast cancer gene 1 and 2 (BRCA 1/2) with Poly (ADP-ribose) polymerase (PARP) inhibitors or the PI3K/AKT/mTOR pathway provides therapeutic options. The advent of antibody-drug conjugates (ADCs) like trastuzumab deruxtecan (T-DXd) and novel agents targeting Trophoblast cell surface antigen-2 (Trop-2) introduces further complexity, underscoring the need for early intervention targeting specific genomic alterations in metastatic BC.

In this study, we employed formaldehyde cross-linking followed by ERα immunoprecipitation and mass spectrometry to reveal that fulvestrant, the first FDA-approved SERD, induces the interaction between ERα and SUMO E3 ligases PIAS1 and PIAS2. In addition, raloxifene (a SERM) and elacestrant (the first FDA-approved oral SERD) were identified as compounds that similarly induce ERα SUMOylation and inhibit its chromatin interaction. Our findings reveal a mechanism by which select ERα inhibitors disrupt ERα function through SUMOylation, offering insights for the development of next-generation ERα-targeted therapies.

In this study, by conducting bioinformatics analyses as well as in vitro and in vivo experiments, we identified that NUSAP1 was significantly upregulated in LUAD, with a notable correlation with poorer overall survival, higher scores for immunogenicity and immune infiltration, as well as increased sensitivity to conventional chemotherapeutic drugs such as paclitaxel, docetaxel and vinorelbine in LUAD. Furthermore, we identified entinostat as a novel inhibitor of NUSAP1. Pharmacological targeting ERβ/NUSAP1 axis with fulvestrant (ERβ antagonist) or entinostat (novel NUSAP1 inhibitor) significantly reduced LUAD growth both in vitro and in vivo, which may represent effective alternative therapeutic strategies for patients with LUAD.

Alpelisib (ALP) is a novel phosphoinositide-3-kinase (PI3K) inhibitor recently approved for human receptor-positive, human epidermal growth factor receptor 2-negative, PIK3CA-mutated metastatic breast cancer in combination with fulvestrant. The environmental impact of both methods was assessed using AGREE software and scores for CE and HPLC were calculated to be 0.74 and 0.51, respectively. Because of equally reliable analytical performance and greener analysis, CE should be considered as an alternative technique to HPLC in the analysis of ALP pharmaceutical dosage forms.

P1/2, N=138, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

P2, N=96, Active, not recruiting, Mayo Clinic | N=45 --> 96

P2, N=150, Recruiting, Puma Biotechnology, Inc. | Not yet recruiting --> Recruiting

HIF-1α induced ERβ gene transcription and protein expression in hypoxic cells via binding to HRE in the ESR2 promoter. The suppression of HIF-1α and ERβ both in vitro and in vivo effectively reduced the NSCLC tumor growth.

P2, N=53, Active, not recruiting, UNICANCER | Recruiting --> Active, not recruiting

P3, N=320, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Oct 2024 --> Mar 2026

P2, N=60, Active, not recruiting, Carrick Therapeutics Limited | Recruiting --> Active, not recruiting

P4, N=137, Recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2030 --> Feb 2028 | Trial primary completion date: Feb 2030 --> Jan 2028

P=N/A, N=1900, Recruiting, Pfizer | Trial completion date: Apr 2028 --> Mar 2029

In the liquid biopsies, we detected ESR1 mutations in 42 cases (25.9%) and ERBB2 mutations in six cases (3.7%), arguing for a change in therapy to fulvestrant, elacestrant, or neratinib. Furthermore, 17 cases had detectable TP53 mutations, associated with resistance against endocrine therapy. We conclude that liquid biopsy testing is a noninvasive, sensitive, and helpful method to optimize therapeutic decisions in metastatic BC.

In an analysis of tumor specimens from 32 patients, tumors exhibiting residual cell proliferation after aromatase inhibitor-induced estrogen deprivation with letrozole showed increased mitochondrial content...Pharmacological inhibition of complex I suppressed the tumor-forming potential of persisters and synergized with the anti-estrogen fulvestrant to induce regression of patient-derived xenografts...Endocrine-tolerant persister cancer cells that survive endocrine therapy can cause recurrent disease. Persister cells exhibit increased energetic dependence upon mitochondria for survival and tumor re-growth potential.

P3, N=560, Recruiting, AstraZeneca

Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life.

P3, N=275, Completed, Genor Biopharma Co., Ltd. | Recruiting --> Completed

P3, N=500, Recruiting, AstraZeneca | Trial completion date: Jul 2030 --> Oct 2030

Outcomes in the Japan subgroup were broadly similar to those of the global population, supporting the clinical benefit of capivasertib-fulvestrant in treating HR-positive/HER2-negative advanced breast cancer that has progressed on, or after, an endocrine-based regimen.

P2, N=120, Not yet recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Jan 2027 --> May 2027

P2, N=38, Not yet recruiting, OHSU Knight Cancer Institute