The main purpose of this study is to measure how well imlunestrant works compared to standard hormone therapy, and how well imlunestrant with abemaciclib work compared to imlunestrant in participants with breast cancer that is estrogen receptor positive (ER+) and human epidermal receptor 2 negative (HER2-). Participants must have breast cancer that is advanced or has spread to another part of the body. Study participation could last up to 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
874
Administered orally.
Administered orally.
Administered IM.
Administered orally.
Ironwood Cancer & Research Centers
Chandler, Arizona, United States
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
Marin Cancer Care
Greenbrae, California, United States
University of California Davis (UC Davis) Comprehensive Cancer Center
Sacramento, California, United States
Sharp Memorial Hospital
San Diego, California, United States
Investigator-assessed Progression Free Survival (PFS) (Between Arm A and Arm B)
PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).
Time frame: Randomization to the date of first documented progression of disease or death from any cause (up to 28 months)
Investigator-assessed PFS (Between Arm C and Arm A)
PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).
Time frame: Randomization to the date of first documented progression of disease or death from any cause (up to 26 months)
Investigator-assessed PFS in the Estrogen Receptor 1 (ESR1)-Mutation Detected Population (Between Arm A and Arm B)
PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).
Time frame: Randomization to the date of first documented progression of disease or death from any cause (up to 28 months)
Blinded Independent Review Committee (BIRC) Assessed PFS (Between Arm A and Arm B)
PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).
Time frame: Randomization to the date of first documented progression of disease or death from any cause (up to 28 months)
Blinded Independent Review Committee (BIRC) Assessed PFS (Between Arm C and Arm A)
PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).
Time frame: Randomization to the date of first documented progression of disease or death from any cause (up to 25 months)
Percentage of Participants With Investigator-assessed Objective Response Rate (ORR) (Between Arm A and Arm B)
ORR was the best confirmed overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.
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Banner MD Anderson Cancer Center at McKee Medical Center
Loveland, Colorado, United States
Clermont Oncology Center
Clermont, Florida, United States
University of Florida College of Medicine
Gainesville, Florida, United States
Mid Florida Hematology and Oncology Center
Orange City, Florida, United States
Florida Cancer Specialists
Sarasota, Florida, United States
...and 233 more locations
Time frame: Randomization until measured progressive disease (up to 28 months)
Investigator-assessed Duration of Response (DoR) (Between Arm A and Arm B)
DoR is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).
Time frame: From Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 26 Months)
Percentage of Participants With Investigator-assessed Clinical Benefit Rate (CBR) (Between Arm A and Arm B)
CBR was the best confirmed overall tumor response of stable disease (SD) for greater than or equal to (≥) 24 weeks, CR or PR as defined by RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Time frame: Randomization until measured progressive disease (up to 28 months)
Percentage of Participants With Investigator-assessed Objective Response Rate (ORR) (Between Arm C and Arm A)
ORR was the best confirmed overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.
Time frame: Randomization until measured progressive disease (up to 26 months)
Investigator-assessed Duration of Response (DoR) (Between Arm C and Arm A)
DoR is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).
Time frame: From Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 19 Months)
Percentage of Participants With Investigator-assessed Clinical Benefit Rate (CBR) (Between Arm C and Arm A)
CBR was the best confirmed overall tumor response of stable disease (SD) for greater than or equal to (≥) 24 weeks, CR or PR as defined by RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Time frame: Randomization until measured progressive disease (up to 26 months)
Time to Sustained Worsening of the "Worst Pain" as Measured by Worst Pain NRS (Between Arm A and Arm B)
Time to sustained worsening of worst pain is defined as the time from randomization to the first increase (≥2 points) in the weekly average of the worst pain score, with confirmation in the next consecutive week. It was measured by the Worst Pain Numeric Rating Scale (NRS). NRS is a single-item, participant-administered, 11-point horizontal scale ranging from 0 to 10, with 0 representing "no pain" and 10 representing "pain as bad as you can imagine." Participants not known to have sustained worsening will be censored at the last documented assessment.
Time frame: Randomization through follow-up (up to 24 months)
Time to Sustained Worsening of the "Worst Pain" as Measured by Worst Pain NRS (Between Arm C and Arm A)
Time to sustained worsening of worst pain is defined as the time from randomization to the first increase (≥2 points) in the weekly average of the worst pain score, with confirmation in the next consecutive week. It was measured by the Worst Pain Numeric Rating Scale (NRS). NRS is a single-item, participant-administered, 11-point horizontal scale ranging from 0 to 10, with 0 representing "no pain" and 10 representing "pain as bad as you can imagine." Participants not known to have sustained worsening will be censored at the last documented assessment.
Time frame: Randomization through follow-up (up to 20 months)
Pharmacokinetics (PK): Plasma Concentration of Imlunestrant
* Sampling timepoints for PK outcome analysis were relative to Imlunestrant dosing. * For Cycle 1 Day 1, sampling occurred at a "single" timepoint within the 2- to 4-hour window after Imlunestrant dosing, with the timepoint varying across analyzed participants.
Time frame: Cycle 1 Day 1 (within 2 to 4 hours post-dose), Cycle 2 Day 1 (Predose), Cycle 3 Day 1 (3 hours post-dose, 5 hours post-dose), Cycle 4 Day 1 (Predose)
Pharmacokinetics (PK): Plasma Concentration of Total Abemaciclib
* Plasma concentration of total abemaciclib is the concentration of the parent abemaciclib and its metabolites in the plasma. * Sampling timepoints for PK outcome analysis were relative to Imlunestrant dosing. * For Cycle 1 Day 1, sampling occurred at a "single" timepoint within the 2- to 4-hour window after Imlunestrant dosing, with the timepoint varying across analyzed participants.
Time frame: Cycle 1 Day 1 (within 2 to 4 hours post-dose), Cycle 2 Day 1 (Predose), Cycle 3 Day 1 (3 hours post-dose, 5 hours post-dose), Cycle 4 Day 1 (Predose)
Overall Survival (OS) in the ITT Population
OS in the ITT population
Time frame: Randomization until death from any cause (estimated as up to 5 years)
OS in the ESR1-mutation Detected Population
OS in the ESR1-mutation detected population
Time frame: Randomization until death from any cause (estimated as up to 5 years)
Blinded Independent Review Committee (BIRC) Assessed PFS in the ESR1-Mutation Detected Population (Between Arm A and Arm B)
PFS was defined as the time from randomization to the date of first documented progression of disease or death from any cause in the absence of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, as assessed by investigator. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).
Time frame: Randomization to the date of first documented progression of disease or death from any cause (up to 28 months)
Percentage of Participants With Investigator-assessed Objective Response Rate (ORR) in the ESR1-Mutation Detected Population (Between Arm A and Arm B)
ORR was the best confirmed overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.
Time frame: Randomization until measured progressive disease (up to 28 months)
Investigator-assessed Duration of Response (DoR) in the ESR1-Mutation Detected Population (Between Arm A and Arm B)
DoR is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later).
Time frame: From Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 24 Months)
Percentage of Participants With Investigator-assessed Clinical Benefit Rate (CBR) in the ESR1-Mutation Detected Population (Between Arm A and Arm B)
CBR was the best confirmed overall tumor response of stable disease (SD) for greater than or equal to (≥) 24 weeks, CR or PR as defined by RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Time frame: Randomization until measured progressive disease (up to 28 months)