Breast Cancer
Conditions
Brief summary
This Phase 3 clinical study compares the efficacy and safety of elacestrant to the standard of care (SoC) options of fulvestrant or an aromatase inhibitor (AI) in women and men with breast cancer whose disease has advanced on at least one endocrine therapy including a CDK4/6 inhibitor in combination with fulvestrant or an aromatase inhibitor (AI).
Detailed description
This is an international, multicenter, randomized, open-label, active-controlled, event-driven, Phase 3 clinical study comparing the efficacy and safety of elacestrant to the SoC options of fulvestrant or an aromatase inhibitor (AI) in postmenopausal women and in men with advanced or metastatic ER+/HER2- breast cancer, either in participants with tumors that harbor mutations in the ligand binding domain (LBD) of the estrogen receptor 1 (ESR1) gene (ESR1-mut participants) or in all participants regardless of ESR1 status (ESR1-mut and ESR1 wild type \[ESR1-wt\]) and whose disease has relapsed or progressed on at least one and no more than two prior lines of endocrine therapy (with documented progression), which must have included prior CDK4/6 inhibitor therapy in combination with fulvestrant or an aromatase inhibitor (AI) and for whom hormonal monotherapy with one of the SoC drugs (fulvestrant, anastrozole, letrozole, exemestane) is an appropriate treatment option.
Interventions
DRUGElacestrant
400 mg/day once daily oral dosing
DRUGStandard of Care
* Fulvestrant: 500 mg administered intramuscularly (IM) into the buttocks as two 5 mL injections on C1D1, C1D15 and C2D1 and Day 1 of every subsequent 28-day cycle * Anastrozole 1 mg/day on a continuous dosing schedule * Letrozole: 2.5 mg/day on a continuous dosing schedule * Exemestane: 25 mg/day on a continuous dosing schedule
Sponsors
Stemline Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Critical Inclusion Criteria: 1. Participants with proven diagnosis of adenocarcinoma of the breast with evidence of either locally advanced disease not amenable to resection or radiation therapy with curative intent or metastatic disease not amenable to curative therapy. 2. Participants must be appropriate candidates for endocrine monotherapy 3. Participants must have measurable disease or bone only disease with evaluable lesions 4. Female or male participants age ≥ 18 years; female participants must be postmenopausal women, and male participants must not allow pregnancy with their sperm (abstain, do not donate sperm, et cetera). 5. Participants must have ER+ and HER2- tumor status 6. Participants must have previously received at least one and no more than two lines of endocrine therapy for advanced/metastatic breast cancer and meet additional previous treatment criteria. 7. Participants must have received prior treatment with a CDK4/6 inhibitor in combination with either fulvestrant or an aromatase inhibitor (AI) for advanced/metastatic breast cancer (mBC). 8. Participants may have received no more than one line of chemotherapy in the advanced/metastatic setting. Critical
Exclusion criteria
1. Prior treatment with elacestrant or other investigational selective estrogen receptor degrader (SERD) or ER antagonist (D-0502, GDC-0810, GDC-0927, GDC-9545, G1T-48, LSZ102, AZD9496, SAR439859, ZN-c5, H3B-6545, bazedoxifene, lasofoxifene). 2. Prior anticancer or investigational drug treatment within the following windows: 1. Fulvestrant treatment \< 42 days before first dose of study drug 2. Any endocrine therapy \< 14 days before first dose of study drug 3. Chemotherapy \< 21 days before first dose of study drug 4. Any investigational anti-cancer drug therapy \< 28 days or five half-lives (whichever is shorter) before the first dose of study drug. Enrollment of participants whose most recent therapy was an investigational agent should be discussed with the Sponsor 5. Bisphosphonates or RANKL inhibitors initiated or dose changed \< 3 months prior to first dose of study drug 3. Presence of symptomatic visceral disease as defined in protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival in ESR1-mut Participants | From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months) | Progression-free survival based on blinded IRC assessment in ESR1-mut participants defined as the length of time from randomization until the date of objective disease progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as assessed by the blinded IRC or death from any cause. Progression is defined per RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
| Progression-free Survival in All Participants | From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months) | Progression-free survival based on blinded imaging review committee (IRC) assessment in all (ESR1-mut and ESR1-wt) participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival in ESR1-mut Participants | From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months) | Overall survival in ESR1-mut participants, where overall survival is defined as the length of time from randomization until the date of death from any cause. |
| Overall Survival in All Participants | From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months) | Overall survival in all (ESR1-mut and ESR1-wt) participants. |
Countries
Argentina, Australia, Austria, Belgium, Canada, Denmark, France, Greece, Hungary, Ireland, Israel, Italy, Portugal, South Korea, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Elacestrant Participants in Arm 1 will receive elacestrant
Elacestrant: 400 mg/day once daily oral dosing | 239 |
| Standard of Care (SoC) Participants in Arm 2 will receive Investigator's choice of one of the standard-of-care drugs (fulvestrant, anastrozole, letrozole, or exemestane)
Standard of Care:
* Fulvestrant: 500 mg administered intramuscularly (IM) into the buttocks as two 5 mL injections on C1D1, C1D15 and C2D1 and Day 1 of every subsequent 28-day cycle
* Anastrozole 1 mg/day on a continuous dosing schedule
* Letrozole: 2.5 mg/day on a continuous dosing schedule
* Exemestane: 25 mg/day on a continuous dosing schedule | 239 |
| Total | 478 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 69 | 79 |
| Overall Study | Lost to Follow-up | 4 | 1 |
| Overall Study | Participant Noncompliance | 1 | 1 |
| Overall Study | Physician Decision | 1 | 3 |
| Overall Study | Withdrawal by Subject | 12 | 25 |
Baseline characteristics
| Characteristic | Elacestrant | Standard of Care (SoC) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 104 Participants | 111 Participants | 215 Participants |
| Age, Categorical Between 18 and 65 years | 135 Participants | 128 Participants | 263 Participants |
| Body Mass Index | 27.58 kg/m^2 STANDARD_DEVIATION 5.494 | 27.92 kg/m^2 STANDARD_DEVIATION 5.853 | 27.75 kg/m^2 STANDARD_DEVIATION 5.673 |
| Eastern Cooperative Oncology Group Performance Status 0: Fully active, able to carry on all pre-disease performance without restriction | 143 Participants | 135 Participants | 278 Participants |
| Eastern Cooperative Oncology Group Performance Status 1: Restricted in physically strenuous activity but ambulatory & can carry out light, sedentary work | 96 Participants | 103 Participants | 199 Participants |
| Eastern Cooperative Oncology Group Performance Status 2: Ambulatory and capable of all selfcare but unable to carry out any work activities | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 18 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 194 Participants | 191 Participants | 385 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 26 Participants | 30 Participants | 56 Participants |
| Height | 162.27 cm STANDARD_DEVIATION 7.86 | 160.97 cm STANDARD_DEVIATION 7.149 | 161.62 cm STANDARD_DEVIATION 7.532 |
| Sex: Female, Male Female | 233 Participants | 238 Participants | 471 Participants |
| Sex: Female, Male Male | 6 Participants | 1 Participants | 7 Participants |
| Weight | 72.70 kg STANDARD_DEVIATION 16.093 | 72.39 kg STANDARD_DEVIATION 16.39 | 72.55 kg STANDARD_DEVIATION 16.226 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 70 / 239 | 80 / 239 |
| other Total, other adverse events | 215 / 237 | 195 / 230 |
| serious Total, serious adverse events | 29 / 237 | 25 / 230 |
Outcome results
Primary
Progression-free Survival in All Participants
Progression-free survival based on blinded imaging review committee (IRC) assessment in all (ESR1-mut and ESR1-wt) participants.
Time frame: From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Elacestrant | Progression-free Survival in All Participants | 2.79 months |
| Standard of Care (SoC) | Progression-free Survival in All Participants | 1.91 months |
Comparison: The analysis was performed using a stratified Cox Proportional Hazards model with ties=Efron and the stratification factors: prior treatment with fulvestrant (yes vs no) and presence of visceral metastases (yes vs no); the CI calculated using a profile likelihood approach.p-value: 0.001895% CI: [0.552, 0.88]Log Rank
Primary
Progression-free Survival in ESR1-mut Participants
Progression-free survival based on blinded IRC assessment in ESR1-mut participants defined as the length of time from randomization until the date of objective disease progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as assessed by the blinded IRC or death from any cause. Progression is defined per RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Elacestrant | Progression-free Survival in ESR1-mut Participants | 3.78 months |
| Standard of Care (SoC) | Progression-free Survival in ESR1-mut Participants | 1.87 months |
Comparison: The analysis was performed using a stratified Cox Proportional Hazards model with ties=Efron and the stratification factors: prior treatment with fulvestrant (yes vs no) and presence of visceral metastases (yes vs no); the CI calculated using a profile likelihood approach.p-value: 0.000595% CI: [0.387, 0.768]Log Rank
Secondary
Overall Survival in All Participants
Overall survival in all (ESR1-mut and ESR1-wt) participants.
Time frame: From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Elacestrant | Overall Survival in All Participants | NA months |
| Standard of Care (SoC) | Overall Survival in All Participants | NA months |
p-value: 0.069795% CI: [0.536, 1.025]Log Rank
Secondary
Overall Survival in ESR1-mut Participants
Overall survival in ESR1-mut participants, where overall survival is defined as the length of time from randomization until the date of death from any cause.
Time frame: From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Elacestrant | Overall Survival in ESR1-mut Participants | NA months |
| Standard of Care (SoC) | Overall Survival in ESR1-mut Participants | 16.95 months |
Comparison: The analysis was performed using a stratified Cox Proportional Hazards model with ties=Efron and the stratification factors: prior treatment with fulvestrant (yes vs no) and presence of visceral metastases (yes vs no); the CI calculated using a profile likelihood approach.p-value: 0.032595% CI: [0.361, 0.958]Log Rank