SNPMiner Trials (Home Page)
Report for Mutation L536R
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 2 clinical trials
Clinical Trials
1 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 ESR1 Mutation
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 Locally Advanced or Metastatic Breast Cancer Drug: Lasofoxifene 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 --- --- D538G --- --- E380Q --- --- S463P --- --- V534E --- --- P535H --- --- L536H --- --- L536P --- --- L536R ---
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 --- --- D538G --- --- E380Q --- --- S463P --- --- V534E --- --- P535H --- --- L536H --- --- L536P --- --- L536R ---
Primary Outcomes
Description: PFS is defined as the interval from the date of randomization to the earlier date of first documented radiographic progression or death due to any cause
Measure: Progression-Free Survival (PFS) Time: through study completion, an average of 1 yearSecondary Outcomes
Description: CBR is defined as the percentage of all subjects with a complete or partial response; or stable disease for >/=24 weeks.
Measure: Clinical Benefit Rate (CBR) Time: through study completion, an average of 1 yearDescription: ORR is defined as the percentage of subjects with either a complete response (CR) or a partial response (PR) as assessed by the RECIST 1.1 criteria.
Measure: Objective Response Rate (ORR) Time: through study completion, an average of 1 yearDescription: OS is defined as time from randomization to death due to any cause.
Measure: Overall Survival (OS) Time: through study completion, an average of 1 yearDescription: The type, severity (graded by Common Terminology Criteria for Adverse Events [CTCAE version 5.0]), course, duration, seriousness, and relationship to study treatment will be assess at each visit
Measure: Incidence of Adverse Events (AEs) and Serious AEs Time: through study completion, an average of 1 year2 An Open-label, Multicenter Study Evaluating the Safety of Lasofoxifene in Combination With Abemaciclib for the Treatment of Pre- and Postmenopausal Women With Locally Advanced or Metastatic ER+/HER2− Breast Cancer and Have an ESR1 Mutation ( ELAINEII )
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 Metastatic Breast Cancer 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 --- --- D538G --- --- E380Q --- --- S463P --- --- V534E --- --- P535H --- --- L536H --- --- L536P --- --- L536R ---
Primary Outcomes
Description: AEs will be assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Measure: Safety and tolerability of the combination of lasofoxifene and abemaciclib as measured by number of adverse events (AEs), severity of AEs and mortality due to AEs at every scheduled visit. Time: All subjects enrolled in the study will be treated until documented disease progression or until withdrawal for any reason. Safety and tolerability will be assessed from enrollment up to 24 months.Secondary Outcomes
Description: PFS is defined as the time from the date of entry into the study to the earliest date of first documented progression or death due to any cause.
Measure: Progression free survival (PFS) Time: Up to 24 monthsMeasure: Clinical benefit rate (CBR) Time: 24 weeks or longer
Measure: Objective response rate (ORR) Time: All subjects enrolled in the study will be treated until documented disease progression or until withdrawal for any reason. ORR will be assessed up to 24 months.
Description: DoR is from the date of first documented response (CR or PR) to the date of first documented progression of disease or death due to any cause.
Measure: Duration of response (DoR) Time: DoR will be assessed up to 24 months.Description: From the date of entry into the study to the date of first documented response (CR or PR).
Measure: Time to response Time: Time to response will be assessed up to 24 months.Measure: Steady-state pharmacokinetics (PK) sampling for lasofoxifene and abemaciclib concentrations as well as abemaciclib's 3 major metabolites of lasofoxifene and abemaciclib Time: Baseline and pre-dose at every visit starting at Visit 0 (Day 1) through Visit 4 (Week 8) and at the Final/ET visit if this occurred prior to Week 8