This is an open-label, multicenter, single-arm safety study evaluating the safety and tolerability of the lasofoxifene and abemaciclib combination for the treatment of pre- and postmenopausal women with locally advanced or metastatic ER+/HER2- breast cancer who have disease progression on first and/or 2nd lines of hormonal treatment for metastatic disease and have an ESR1 mutation.

NCT04432454

Conditions

1. Metastatic Breast Cancer

Interventions

1. Drug: Lasofoxifene and abemaciclib (VERZENIO (R)).

MeSH:Breast Neoplasms

HPO:Breast carcinoma Neoplasm of the breast

At least one or more of the following ESR1 point mutations as assessed in cell-free circulating tumor DNA (ctDNA) obtained from a blood or tissue sample: Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N. --- Y537S --- --- Y537C ---

This is an open-label, single arm, phase II trial to evaluate the efficacy and safety of 500mg Fulvestrant (Faslodex®) in ESR1 mutated postmenopausal women with hormone receptor positive, HER2 negative locally advanced or metastatic breast cancer after previous aromatase inhibitor therapy. Fifty patients will be enrolled and treated with 500 mg Fulvestrant until disease progression or study closed. Treatment will continue until disease progression, unless any of the criteria for treatment discontinuation are met first. If a patient progresses during the treatment period, the patient must be withdrawn from the treatment and further treatment will be at the investigator's discretion.

NCT03202862

Conditions

1. Breast Neoplasms

Interventions

1. Drug: Fulvestrant

MeSH:Breast Neoplasms

HPO:Breast carcinoma Neoplasm of the breast

The blood sample is clarified to be ESR1 mutated, The mutation should be: Y537C, Y537N, Y537S, S463P and D538G. --- Y537C ---

This is an open label, randomized, multicenter study evaluating the activity of lasofoxifene relative to fulvestrant for the treatment of pre- and postmenopausal women with locally advanced or metastatic ER+/HER2- breast cancer with an acquired ESR1 mutation and who have disease progression on an aromatase inhibitor (AI) in combination with a cyclin dependent kinase (CDK) 4/6 inhibitor. The primary objective is to evaluate the progression free survival (PFS) of 5 mg lasofoxifene relative to fulvestrant for the treatment of pre- and postmenopausal women with locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor 2 negative (HER2-) breast cancer with an estrogen receptor 1 (ESR1) mutation. The secondary objectives are to evaluate: 1. Clinical benefit rate (CBR) and Objective Response Rate (ORR) 2. Duration of response 3. Time to response 4. Overall Survival (OS) 5. Pharmacokinetics of lasofoxifene 6. Quality of life (QoL): Quality of Life (QoL): vaginal assessment scale (VAS) and vulvar assessment scale (VuAS) questionnaires 7. Safety of lasofoxifene 8. Response to various ESR1 mutation (Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N).

NCT03781063

Conditions

1. Locally Advanced or Metastatic Breast Cancer

Interventions

1. Drug: Lasofoxifene
2. Drug: Fulvestrant

MeSH:Breast Neoplasms

HPO:Breast carcinoma Neoplasm of the breast

The secondary objectives are to evaluate: 1. Clinical benefit rate (CBR) and Objective Response Rate (ORR) 2. Duration of response 3. Time to response 4. Overall Survival (OS) 5. Pharmacokinetics of lasofoxifene 6. Quality of life (QoL): Quality of Life (QoL): vaginal assessment scale (VAS) and vulvar assessment scale (VuAS) questionnaires 7. Safety of lasofoxifene 8. Response to various ESR1 mutation (Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N). --- Y537S --- --- Y537C ---

At least one or more of the following point ESR1 mutations as assessed in cell-free circulating tumor DNA (ctDNA) obtained from a blood (plasma) or tissue sample: Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N. --- Y537S --- --- Y537C ---

The investigator propose a prospective study using blood samples (liquid biopsy) of estrogen receptor (ER)-positive metastatic breast cancer (MBC) patients to understand the prevalence of estrogen receptor 1 (ESR1) mutation variants and the correlation with hormonal therapy (HT)-based treatment resistance in Asian ER-positive/human epidermal growth receptor-2 (HER2)-negative MBC population.

NCT04212702

Conditions

1. Metastatic Breast Cancer

Interventions

1. Drug: Hormonal therapy-based treatments

MeSH:Breast Neoplasms

HPO:Breast carcinoma Neoplasm of the breast

PFS of patients who are treated with everolimus plus HT with either ESR1 wild type or different Asian-specific prevalent ESR1 LBD mutation variants such as Y537C. --- Y537C ---

Metastatic Breast Cancer Breast Neoplasms The investigator will use next-generation targeted sequencing covering the entire ESR1 ligand-binding domain (LBD) region to understand 1. the spectrum and prevalence of specific ESR1 mutation variants in Asian women, and 2. the preliminary correlation of Asian-specific prevalent ESR1 LBD mutation variants such as Y537C with treatment efficacy. --- Y537C ---

For the second purpose, the investigator will specifically focus on patients with ESR1 Y537C mutation, while the results from patients with wild type ESR1 and patients with D538G or Y537S mutant will be severed as control for preliminary comparison. --- Y537C ---