A Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer

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)

Population: All participants who were randomly assigned to either arm A or arm C concurrently (including censored). Number of participants censored in Arm C=99, Arm A=64.

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)

Population: All participants who were randomly assigned to either arm A or arm B and had ESR1 mutations detected at baseline (including censored). Number of participants censored in Arm A=29, Arm B=16.

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)

Population: All participants who were randomly assigned to either arm A or arm B (including censored). Number of participants censored in Arm A=94, Arm B=77.

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)

Population: All participants who were randomly assigned to either arm A or arm B (including censored). Number of participants censored in Arm A=171, Arm B=171.

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)

Population: All participants who were randomly assigned to either arm A or arm C concurrently (including censored). Number of participants censored in Arm C=132, Arm A=116.

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)

Population: All participants who were randomly assigned to either arm A or arm B and had ESR1 mutations detected at baseline (including censored). Number of participants censored in Arm A=64, Arm B=47.

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)

Population: All participants who were randomly assigned to either arm A or arm B and had achieved CR or PR responses (including censored). Number of participants censored in Arm A=17, Arm B=7.

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)

Population: All participants who were randomly assigned to either arm C or arm A and had achieved CR or PR responses (including censored). Number of participants censored in Arm C=30, Arm A=11.

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)

Population: All participants who were randomly assigned to either arm A or arm B, had ESR1 mutations detected at baseline and had achieved CR or PR responses (including censored). Number of participants censored in Arm A=5, Arm B=0.

OS in the ESR1-mutation detected population

Time frame: Randomization until death from any cause (estimated as up to 5 years)

OS in the ITT population

Time frame: Randomization until death from any cause (estimated as up to 5 years)

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)

Population: All participants who were randomly assigned to either arm A or 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 26 months)

Population: All participants who were randomly assigned to either arm A or arm C concurrently.

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)

Population: All participants who were randomly assigned to either arm A or arm B and had ESR1 mutations detected at baseline.

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)

Population: All participants who were randomly assigned to either arm A or 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 26 months)

Population: All participants who were randomly assigned to either arm A or arm C concurrently.

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)

Population: All participants who were randomly assigned to either arm A or arm B and had ESR1 mutations detected at baseline.

* 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)

Population: All randomised participants who received at least 1 dose of study drug and had evaluable PK data for this outcome.

* 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)

Population: All randomised participants who received at least 1 dose of study drug and had evaluable PK data for this outcome.

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)

Population: All participants who were randomly assigned to either arm A or arm B and had at least one NRS assessment available (including censored). Number of participants censored in Arm A=258, Arm B=267.

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)

Population: All participants who were randomly assigned to either arm A or arm C concurrently and had at least one NRS assessment available (including censored). Number of participants censored in Arm C=163, Arm A=162.