Trial Outcomes & Findings for A Study of Giredestrant (GDC-9545) in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer (NCT NCT03916744)

Last Updated: 2023-03-10

Results Overview

The biological response to the study treatment was assessed by measuring changes in cell proliferation (Ki67 expression) using formalin-fixed paraffin-embedded histopathology sections of the tumor biopsy specimens taken at baseline and at day of surgery. Baseline was defined as a sample taken prior to initiation of study drug. The results show the proportion of nuclei staining Ki67-positive (Ki67+) in the tumor biopsy sample taken post-treatment (at surgery) relative to that in the pre-treatment sample (at baseline).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

75 participants

Primary outcome timeframe

Baseline and Surgery (Day 15)

Results posted on

2023-03-10

Participant Flow

Participant milestones

Participant milestones
Measure	Giredestrant 10 mg Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Overall Study STARTED	17	40	18
Overall Study Received at Least One Dose of Study Drug	17	40	17
Overall Study COMPLETED	17	39	16
Overall Study NOT COMPLETED	0	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Giredestrant 10 mg Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Overall Study Withdrawal by Subject	0	1	2

Baseline Characteristics

Age was missing for one participant in the giredestrant 100 mg arm because of early withdrawal from the study.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Giredestrant 10 mg n=17 Participants Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg n=40 Participants Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg n=18 Participants Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Total n=75 Participants Total of all reporting groups
Age, Continuous	63.4 Years STANDARD_DEVIATION 8.9 • n=17 Participants • Age was missing for one participant in the giredestrant 100 mg arm because of early withdrawal from the study.	64.1 Years STANDARD_DEVIATION 9.4 • n=40 Participants • Age was missing for one participant in the giredestrant 100 mg arm because of early withdrawal from the study.	64.1 Years STANDARD_DEVIATION 7.7 • n=17 Participants • Age was missing for one participant in the giredestrant 100 mg arm because of early withdrawal from the study.	63.9 Years STANDARD_DEVIATION 8.8 • n=74 Participants • Age was missing for one participant in the giredestrant 100 mg arm because of early withdrawal from the study.
Sex: Female, Male Female	17 Participants n=17 Participants	40 Participants n=40 Participants	18 Participants n=18 Participants	75 Participants n=75 Participants
Sex: Female, Male Male	0 Participants n=17 Participants	0 Participants n=40 Participants	0 Participants n=18 Participants	0 Participants n=75 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=17 Participants	4 Participants n=40 Participants	0 Participants n=18 Participants	4 Participants n=75 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=17 Participants	19 Participants n=40 Participants	6 Participants n=18 Participants	29 Participants n=75 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	13 Participants n=17 Participants	17 Participants n=40 Participants	12 Participants n=18 Participants	42 Participants n=75 Participants
Race/Ethnicity, Customized Asian	0 Participants n=17 Participants	0 Participants n=40 Participants	1 Participants n=18 Participants	1 Participants n=75 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=17 Participants	1 Participants n=40 Participants	0 Participants n=18 Participants	1 Participants n=75 Participants
Race/Ethnicity, Customized White	16 Participants n=17 Participants	38 Participants n=40 Participants	17 Participants n=18 Participants	71 Participants n=75 Participants
Race/Ethnicity, Customized Multiple	1 Participants n=17 Participants	0 Participants n=40 Participants	0 Participants n=18 Participants	1 Participants n=75 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=17 Participants	1 Participants n=40 Participants	0 Participants n=18 Participants	1 Participants n=75 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline ECOG Performance Status of 0	17 Participants n=17 Participants • ECOG performance status was missing for one participant in the giredestrant 100 mg arm because of early withdrawal from the study.	36 Participants n=40 Participants • ECOG performance status was missing for one participant in the giredestrant 100 mg arm because of early withdrawal from the study.	17 Participants n=17 Participants • ECOG performance status was missing for one participant in the giredestrant 100 mg arm because of early withdrawal from the study.	70 Participants n=74 Participants • ECOG performance status was missing for one participant in the giredestrant 100 mg arm because of early withdrawal from the study.
Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline ECOG Performance Status of 1	0 Participants n=17 Participants • ECOG performance status was missing for one participant in the giredestrant 100 mg arm because of early withdrawal from the study.	4 Participants n=40 Participants • ECOG performance status was missing for one participant in the giredestrant 100 mg arm because of early withdrawal from the study.	0 Participants n=17 Participants • ECOG performance status was missing for one participant in the giredestrant 100 mg arm because of early withdrawal from the study.	4 Participants n=74 Participants • ECOG performance status was missing for one participant in the giredestrant 100 mg arm because of early withdrawal from the study.
Initial Staging of Breast Cancer (Breast Cancer History) Stage I	9 Participants n=17 Participants	19 Participants n=40 Participants	10 Participants n=18 Participants	38 Participants n=75 Participants
Initial Staging of Breast Cancer (Breast Cancer History) Stage II	8 Participants n=17 Participants	21 Participants n=40 Participants	7 Participants n=18 Participants	36 Participants n=75 Participants
Initial Staging of Breast Cancer (Breast Cancer History) Stage III	0 Participants n=17 Participants	0 Participants n=40 Participants	1 Participants n=18 Participants	1 Participants n=75 Participants
Tumor Grade (Breast Cancer History) Grade 1	6 Participants n=17 Participants	13 Participants n=40 Participants	4 Participants n=18 Participants	23 Participants n=75 Participants
Tumor Grade (Breast Cancer History) Grade 2	9 Participants n=17 Participants	23 Participants n=40 Participants	12 Participants n=18 Participants	44 Participants n=75 Participants
Tumor Grade (Breast Cancer History) Grade 3	2 Participants n=17 Participants	4 Participants n=40 Participants	2 Participants n=18 Participants	8 Participants n=75 Participants
Nodal Status (Breast Cancer History) Negative	14 Participants n=17 Participants	37 Participants n=40 Participants	17 Participants n=18 Participants	68 Participants n=75 Participants
Nodal Status (Breast Cancer History) Positive	2 Participants n=17 Participants	3 Participants n=40 Participants	1 Participants n=18 Participants	6 Participants n=75 Participants
Nodal Status (Breast Cancer History) Missing	1 Participants n=17 Participants	0 Participants n=40 Participants	0 Participants n=18 Participants	1 Participants n=75 Participants

PRIMARY outcome

Timeframe: Baseline and Surgery (Day 15)

Population: Efficacy Evaluable Population: all participants who 1) had non-missing baseline and post-baseline Ki67 results available, 2) did not discontinue early from the study, 3) had taken at least 12 doses, and 4) had no more than one modified dose. A total of 10 participants (2 in the 10mg cohort, 5 in the 30mg cohort, and 3 in the 100mg cohort) were excluded from efficacy evaluation for not meeting the criteria.

Outcome measures

Outcome measures
Measure	Giredestrant 10 mg n=15 Participants Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg n=35 Participants Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg n=15 Participants Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	All Participants, Efficacy: Giredestrant (10, 30, or 100 mg) n=65 Participants This analysis set includes all efficacy-evaluable participants. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Change From Baseline in Tumor Cell Proliferation, as Measured by the Proportion of Nuclei Staining Ki67-Positive at Surgery Relative to Baseline in Pre- and Post-Treatment Tumor Biopsy Samples	0.20 Proportion of Ki67+ nuclei Interval 0.12 to 0.31	0.24 Proportion of Ki67+ nuclei Interval 0.18 to 0.32	0.22 Proportion of Ki67+ nuclei Interval 0.13 to 0.37	0.22 Proportion of Ki67+ nuclei Interval 0.18 to 0.28

PRIMARY outcome

Timeframe: Baseline and Surgery (Day 15)

The biological response to the study treatment was assessed by measuring changes in cell proliferation (Ki67 expression) using formalin-fixed paraffin-embedded histopathology sections of the tumor biopsy specimens taken at baseline and at day of surgery. Baseline was defined as a sample taken prior to initiation of study drug. The results show the percentage of nuclei staining Ki67-positive (Ki67+) in the pre- and post-treatment tumor biopsy samples (taken at baseline and surgery, respectively) and the absolute difference in the percentage of Ki67+ nuclei between the two samples (calculated as surgery minus baseline).

Outcome measures

Outcome measures
Measure	Giredestrant 10 mg n=15 Participants Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg n=35 Participants Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg n=15 Participants Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	All Participants, Efficacy: Giredestrant (10, 30, or 100 mg) n=65 Participants This analysis set includes all efficacy-evaluable participants. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Change From Baseline in Tumor Cell Proliferation, as Measured by the Difference in the Percentage of Nuclei Staining Ki67-Positive at Surgery Compared With Baseline in Pre- and Post-Treatment Tumor Biopsy Samples Baseline (BL) - Value at Visit	15.70 Percentage of nuclei Ki67+ Standard Deviation 9.25	15.10 Percentage of nuclei Ki67+ Standard Deviation 11.23	15.58 Percentage of nuclei Ki67+ Standard Deviation 9.95	15.35 Percentage of nuclei Ki67+ Standard Deviation 10.36
Change From Baseline in Tumor Cell Proliferation, as Measured by the Difference in the Percentage of Nuclei Staining Ki67-Positive at Surgery Compared With Baseline in Pre- and Post-Treatment Tumor Biopsy Samples Surgery - Value at Visit	4.22 Percentage of nuclei Ki67+ Standard Deviation 4.70	4.12 Percentage of nuclei Ki67+ Standard Deviation 4.35	4.08 Percentage of nuclei Ki67+ Standard Deviation 3.80	4.13 Percentage of nuclei Ki67+ Standard Deviation 4.25
Change From Baseline in Tumor Cell Proliferation, as Measured by the Difference in the Percentage of Nuclei Staining Ki67-Positive at Surgery Compared With Baseline in Pre- and Post-Treatment Tumor Biopsy Samples Change from BL at Surgery (Surgery minus BL)	-11.49 Percentage of nuclei Ki67+ Standard Deviation 7.84	-10.98 Percentage of nuclei Ki67+ Standard Deviation 8.53	-11.49 Percentage of nuclei Ki67+ Standard Deviation 8.23	-11.21 Percentage of nuclei Ki67+ Standard Deviation 8.18

SECONDARY outcome

Timeframe: From Baseline to Day 43

All adverse events (AEs) were recorded and the investigator independently assessed the seriousness and severity of each AE. AE severity was graded on a scale from 1 to 5 using the NCI-CTCAE v5.0; any events not specifically listed in the scale were defined as: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening; and Grade 5 is death related to an AE. Investigators used their knowledge of the patient, the circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an AE was considered to be related to the study drug.

Outcome measures

Outcome measures
Measure	Giredestrant 10 mg n=17 Participants Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg n=40 Participants Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg n=17 Participants Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	All Participants, Efficacy: Giredestrant (10, 30, or 100 mg) n=74 Participants This analysis set includes all efficacy-evaluable participants. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Number of Participants With at Least One Adverse Event and by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) Related Serious AE	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With at Least One Adverse Event and by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) Any Adverse Event (AE)	12 Participants	27 Participants	14 Participants	53 Participants
Number of Participants With at Least One Adverse Event and by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) AE with Fatal Outcome	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With at Least One Adverse Event and by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) Serious AE	1 Participants	2 Participants	1 Participants	4 Participants
Number of Participants With at Least One Adverse Event and by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) AE Leading to Withdrawal from Study Drug	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With at Least One Adverse Event and by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) AE Leading to Interruption of Study Drug	1 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With at Least One Adverse Event and by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) Related AE	7 Participants	17 Participants	8 Participants	32 Participants
Number of Participants With at Least One Adverse Event and by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) Grade 3-4 AE	1 Participants	3 Participants	1 Participants	5 Participants
Number of Participants With at Least One Adverse Event and by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) Related Grade 3-4 AE	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Days 1, 8, and 15

Vital signs, which included diastolic and systolic blood pressure, pulse rate, and body temperature, were measured while the participant was sitting and according to institutional practices. Any of the vital signs that were outside of the normal reference range (in the specified direction - low or high) were considered abnormalities. Not every abnormality qualified as an adverse event (AE). A vital sign result had to be reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment.

Outcome measures

Outcome measures
Measure	Giredestrant 10 mg n=17 Participants Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg n=40 Participants Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg n=17 Participants Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	All Participants, Efficacy: Giredestrant (10, 30, or 100 mg) n=74 Participants This analysis set includes all efficacy-evaluable participants. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Percentage of Participants With Abnormal Vital Signs During Treatment Diastolic Blood Pressure - Low	5.9 Percentage of participants	12.5 Percentage of participants	23.5 Percentage of participants	13.5 Percentage of participants
Percentage of Participants With Abnormal Vital Signs During Treatment Diastolic Blood Pressure - High	64.7 Percentage of participants	35.0 Percentage of participants	11.8 Percentage of participants	36.5 Percentage of participants
Percentage of Participants With Abnormal Vital Signs During Treatment Systolic Blood Pressure - High	82.4 Percentage of participants	70.0 Percentage of participants	58.8 Percentage of participants	70.3 Percentage of participants
Percentage of Participants With Abnormal Vital Signs During Treatment Pulse Rate - Low	11.8 Percentage of participants	27.5 Percentage of participants	64.7 Percentage of participants	32.4 Percentage of participants
Percentage of Participants With Abnormal Vital Signs During Treatment Pulse Rate - High	0 Percentage of participants	2.5 Percentage of participants	0 Percentage of participants	1.4 Percentage of participants
Percentage of Participants With Abnormal Vital Signs During Treatment Body Temperature - Low	88.2 Percentage of participants	82.5 Percentage of participants	94.1 Percentage of participants	86.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43)

Population: Safety Evaluable Population: all participants who received at least one dose of giredestrant. One participant from the ITT population did not receive the study drug because of early withdrawal from the study. The number analyzed indicates all participants who had a non-missing assessment at a given timepoint.

Pulse rate was measured while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit. Baseline was defined as the participant's last value prior to initiation of study drug.

Outcome measures

Outcome measures
Measure	Giredestrant 10 mg n=17 Participants Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg n=40 Participants Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg n=17 Participants Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	All Participants, Efficacy: Giredestrant (10, 30, or 100 mg) n=74 Participants This analysis set includes all efficacy-evaluable participants. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Change From Baseline in Pulse Rate Baseline (BL) - Value at Visit	75.3 beats per minute Standard Deviation 9.5	72.6 beats per minute Standard Deviation 11.1	72.1 beats per minute Standard Deviation 10.6	73.1 beats per minute Standard Deviation 10.6
Change From Baseline in Pulse Rate Change from BL at Day 8	1.4 beats per minute Standard Deviation 8.5	-1.9 beats per minute Standard Deviation 11.3	-11.1 beats per minute Standard Deviation 10.6	-3.1 beats per minute Standard Deviation 11.3
Change From Baseline in Pulse Rate Change from BL at Surgery	2.4 beats per minute Standard Deviation 9.7	-3.8 beats per minute Standard Deviation 10.7	-13.9 beats per minute Standard Deviation 10.8	-4.5 beats per minute Standard Deviation 11.8
Change From Baseline in Pulse Rate Change from BL at Post-Surgery	2.2 beats per minute Standard Deviation 12.0	3.5 beats per minute Standard Deviation 11.4	4.2 beats per minute Standard Deviation 11.3	3.4 beats per minute Standard Deviation 11.4
Change From Baseline in Pulse Rate Change from BL at Post-BL Minimum	-4.2 beats per minute Standard Deviation 9.2	-7.4 beats per minute Standard Deviation 9.9	-14.4 beats per minute Standard Deviation 10.7	-8.3 beats per minute Standard Deviation 10.4
Change From Baseline in Pulse Rate Change from BL at Post-BL Maximum	9.5 beats per minute Standard Deviation 7.2	6.7 beats per minute Standard Deviation 11.1	4.8 beats per minute Standard Deviation 10.0	6.9 beats per minute Standard Deviation 10.1

SECONDARY outcome

Timeframe: Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43)

Systolic blood pressure was measured while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit. Baseline was defined as the participant's last value prior to initiation of study drug.

Outcome measures

Outcome measures
Measure	Giredestrant 10 mg n=17 Participants Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg n=40 Participants Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg n=17 Participants Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	All Participants, Efficacy: Giredestrant (10, 30, or 100 mg) n=74 Participants This analysis set includes all efficacy-evaluable participants. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Change From Baseline in Systolic Blood Pressure Baseline (BL) - Value at Visit	135.4 millimetres of mercury (mmHg) Standard Deviation 18.6	128.0 millimetres of mercury (mmHg) Standard Deviation 14.2	129.4 millimetres of mercury (mmHg) Standard Deviation 14.7	130.0 millimetres of mercury (mmHg) Standard Deviation 15.5
Change From Baseline in Systolic Blood Pressure Change from BL at Day 8	-1.1 millimetres of mercury (mmHg) Standard Deviation 12.3	2.9 millimetres of mercury (mmHg) Standard Deviation 14.0	-7.9 millimetres of mercury (mmHg) Standard Deviation 14.3	-0.3 millimetres of mercury (mmHg) Standard Deviation 14.2
Change From Baseline in Systolic Blood Pressure Change from BL at Surgery	-2.2 millimetres of mercury (mmHg) Standard Deviation 15.7	5.7 millimetres of mercury (mmHg) Standard Deviation 15.2	-1.4 millimetres of mercury (mmHg) Standard Deviation 17.3	2.2 millimetres of mercury (mmHg) Standard Deviation 16.0
Change From Baseline in Systolic Blood Pressure Change from BL at Post-Surgery	-2.1 millimetres of mercury (mmHg) Standard Deviation 14.6	1.0 millimetres of mercury (mmHg) Standard Deviation 13.2	-3.2 millimetres of mercury (mmHg) Standard Deviation 15.3	-0.7 millimetres of mercury (mmHg) Standard Deviation 13.9
Change From Baseline in Systolic Blood Pressure Change from BL at Post-BL Minimum	-9.5 millimetres of mercury (mmHg) Standard Deviation 12.0	-5.5 millimetres of mercury (mmHg) Standard Deviation 11.2	-12.5 millimetres of mercury (mmHg) Standard Deviation 14.6	-8.0 millimetres of mercury (mmHg) Standard Deviation 12.4
Change From Baseline in Systolic Blood Pressure Change from BL at Post-BL Maximum	5.9 millimetres of mercury (mmHg) Standard Deviation 13.6	11.8 millimetres of mercury (mmHg) Standard Deviation 13.4	3.2 millimetres of mercury (mmHg) Standard Deviation 15.2	8.5 millimetres of mercury (mmHg) Standard Deviation 14.2

SECONDARY outcome

Timeframe: Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43)

Diastolic blood pressure was measured while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit. Baseline was defined as the participant's last value prior to initiation of study drug.

Outcome measures

Outcome measures
Measure	Giredestrant 10 mg n=17 Participants Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg n=40 Participants Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg n=17 Participants Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	All Participants, Efficacy: Giredestrant (10, 30, or 100 mg) n=74 Participants This analysis set includes all efficacy-evaluable participants. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Change From Baseline in Diastolic Blood Pressure Change from BL at Surgery	-3.2 millimetres of mercury (mmHg) Standard Deviation 7.9	-2.1 millimetres of mercury (mmHg) Standard Deviation 12.5	-8.3 millimetres of mercury (mmHg) Standard Deviation 10.7	-3.7 millimetres of mercury (mmHg) Standard Deviation 11.2
Change From Baseline in Diastolic Blood Pressure Change from BL at Post-Surgery	4.1 millimetres of mercury (mmHg) Standard Deviation 8.0	0.1 millimetres of mercury (mmHg) Standard Deviation 10.5	-4.5 millimetres of mercury (mmHg) Standard Deviation 9.8	0.0 millimetres of mercury (mmHg) Standard Deviation 10.1
Change From Baseline in Diastolic Blood Pressure Baseline (BL) - Value at Visit	78.4 millimetres of mercury (mmHg) Standard Deviation 10.3	75.2 millimetres of mercury (mmHg) Standard Deviation 10.7	76.9 millimetres of mercury (mmHg) Standard Deviation 10.8	76.3 millimetres of mercury (mmHg) Standard Deviation 10.6
Change From Baseline in Diastolic Blood Pressure Change from BL at Day 8	-3.4 millimetres of mercury (mmHg) Standard Deviation 7.3	-0.5 millimetres of mercury (mmHg) Standard Deviation 7.4	-9.5 millimetres of mercury (mmHg) Standard Deviation 10.3	-3.1 millimetres of mercury (mmHg) Standard Deviation 8.7
Change From Baseline in Diastolic Blood Pressure Change from BL at Post-BL Minimum	-6.4 millimetres of mercury (mmHg) Standard Deviation 6.6	-6.2 millimetres of mercury (mmHg) Standard Deviation 8.7	-12.2 millimetres of mercury (mmHg) Standard Deviation 8.5	-7.6 millimetres of mercury (mmHg) Standard Deviation 8.5
Change From Baseline in Diastolic Blood Pressure Change from BL at Post-BL Maximum	5.6 millimetres of mercury (mmHg) Standard Deviation 7.0	3.8 millimetres of mercury (mmHg) Standard Deviation 10.8	-2.8 millimetres of mercury (mmHg) Standard Deviation 9.2	2.7 millimetres of mercury (mmHg) Standard Deviation 10.1

SECONDARY outcome

Timeframe: Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43)

Body temperature was measured according to institutional practice. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit. Baseline was defined as the participant's last value prior to initiation of study drug.

Outcome measures

Outcome measures
Measure	Giredestrant 10 mg n=17 Participants Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg n=40 Participants Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg n=17 Participants Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	All Participants, Efficacy: Giredestrant (10, 30, or 100 mg) n=74 Participants This analysis set includes all efficacy-evaluable participants. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Change From Baseline in Body Temperature Baseline (BL) - Value at Visit	36.36 degrees Celsius (C) Standard Deviation 0.48	36.41 degrees Celsius (C) Standard Deviation 0.38	36.25 degrees Celsius (C) Standard Deviation 0.24	36.36 degrees Celsius (C) Standard Deviation 0.38
Change From Baseline in Body Temperature Change from BL at Day 8	-0.03 degrees Celsius (C) Standard Deviation 0.41	-0.06 degrees Celsius (C) Standard Deviation 0.51	-0.09 degrees Celsius (C) Standard Deviation 0.43	-0.06 degrees Celsius (C) Standard Deviation 0.47
Change From Baseline in Body Temperature Change from BL at Surgery	0.14 degrees Celsius (C) Standard Deviation 0.51	-0.09 degrees Celsius (C) Standard Deviation 0.46	-0.18 degrees Celsius (C) Standard Deviation 0.43	-0.05 degrees Celsius (C) Standard Deviation 0.47
Change From Baseline in Body Temperature Change from BL at Post-Surgery	-0.03 degrees Celsius (C) Standard Deviation 0.56	-0.05 degrees Celsius (C) Standard Deviation 0.39	-0.11 degrees Celsius (C) Standard Deviation 0.50	-0.06 degrees Celsius (C) Standard Deviation 0.45
Change From Baseline in Body Temperature Change from BL at Post-BL Minimum	-0.20 degrees Celsius (C) Standard Deviation 0.52	-0.34 degrees Celsius (C) Standard Deviation 0.44	-0.39 degrees Celsius (C) Standard Deviation 0.42	-0.32 degrees Celsius (C) Standard Deviation 0.45
Change From Baseline in Body Temperature Change from BL at Post-BL Maximum	0.28 degrees Celsius (C) Standard Deviation 0.42	0.15 degrees Celsius (C) Standard Deviation 0.44	0.12 degrees Celsius (C) Standard Deviation 0.32	0.17 degrees Celsius (C) Standard Deviation 0.41

SECONDARY outcome

Timeframe: Baseline, Days 1, 8, and 15

Population: Safety Evaluable Population: the number of participants analyzed includes all participants who received at least one dose of giredestrant. The number analyzed for a given laboratory parameter represents the number of participants without an abnormality (in the specified direction) at baseline for that parameter.

Laboratory parameters for hematology will be measured and compared with a standard reference range. Any of the laboratory test results that were outside of a parameter's normal reference range (in the specified direction - low or high) were considered abnormalities. Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment.

Outcome measures

Outcome measures
Measure	Giredestrant 10 mg n=17 Participants Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg n=40 Participants Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg n=17 Participants Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	All Participants, Efficacy: Giredestrant (10, 30, or 100 mg) n=74 Participants This analysis set includes all efficacy-evaluable participants. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Percentage of Participants With Laboratory Abnormalities in Hematology Tests During Treatment, Among Participants Without the Abnormality at Baseline Hematocrit - Low	0 Percentage of participants	3.2 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Hematology Tests During Treatment, Among Participants Without the Abnormality at Baseline Hematocrit - High	22.2 Percentage of participants	0 Percentage of participants	0 Percentage of participants	4.3 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Hematology Tests During Treatment, Among Participants Without the Abnormality at Baseline Hemoglobin - Low	10.0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Hematology Tests During Treatment, Among Participants Without the Abnormality at Baseline Hemoglobin - High	0 Percentage of participants	3.1 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Hematology Tests During Treatment, Among Participants Without the Abnormality at Baseline Lymphocytes, Absolute Count (Abs) - Low	0 Percentage of participants	3.1 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Hematology Tests During Treatment, Among Participants Without the Abnormality at Baseline Lymphocytes, Abs - High	0 Percentage of participants	3.2 Percentage of participants	12.5 Percentage of participants	4.1 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Hematology Tests During Treatment, Among Participants Without the Abnormality at Baseline Neutrophils, Total, Abs - Low	0 Percentage of participants	3.2 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Hematology Tests During Treatment, Among Participants Without the Abnormality at Baseline Erythrocytes - Low	22.2 Percentage of participants	6.7 Percentage of participants	0 Percentage of participants	8.5 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Hematology Tests During Treatment, Among Participants Without the Abnormality at Baseline Total Leukocyte Count - Low	0 Percentage of participants	3.1 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Days 1, 8, and 15

Laboratory parameters for blood chemistry and coagulation were measured and compared with a standard reference range. Any of the laboratory test results that were outside of a parameter's normal reference range (in the specified direction - low or high) were considered abnormalities. Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. SGPT/ALT = alanine aminotransferase; SGOT/AST = aspartate aminotransferase

Outcome measures

Outcome measures
Measure	Giredestrant 10 mg n=17 Participants Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg n=40 Participants Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg n=17 Participants Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	All Participants, Efficacy: Giredestrant (10, 30, or 100 mg) n=74 Participants This analysis set includes all efficacy-evaluable participants. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Albumin - Low	0 Percentage of participants	3.3 Percentage of participants	0 Percentage of participants	2.1 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Albumin - High	0 Percentage of participants	3.3 Percentage of participants	0 Percentage of participants	2.1 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Alkaline Phosphatase - High	0 Percentage of participants	3.4 Percentage of participants	0 Percentage of participants	2.3 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline SGPT/ALT - High	0 Percentage of participants	6.7 Percentage of participants	14.3 Percentage of participants	6.5 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline SGOT/AST - High	0 Percentage of participants	3.1 Percentage of participants	14.3 Percentage of participants	4.2 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Bicarbonate HCO3 - Low	0 Percentage of participants	3.1 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Bicarbonate HCO3 - High	16.7 Percentage of participants	9.5 Percentage of participants	40.0 Percentage of participants	15.6 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Blood Urea Nitrogen - High	10.0 Percentage of participants	3.1 Percentage of participants	0 Percentage of participants	4.1 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Calcium - High	0 Percentage of participants	3.1 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Carbon Dioxide - High	33.3 Percentage of participants	25.0 Percentage of participants	0 Percentage of participants	25.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Chloride - Low	10.0 Percentage of participants	3.2 Percentage of participants	12.5 Percentage of participants	6.1 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Chloride - High	0 Percentage of participants	9.4 Percentage of participants	0 Percentage of participants	6.3 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Creatinine - High	0 Percentage of participants	3.1 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Direct Bilirubin - Low	10.0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	2.4 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Direct Bilirubin - High	11.1 Percentage of participants	3.4 Percentage of participants	0 Percentage of participants	4.3 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Glucose, Fasting - High	0 Percentage of participants	31.3 Percentage of participants	0 Percentage of participants	19.2 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Glucose, Fasting Unknown - High	33.3 Percentage of participants	21.4 Percentage of participants	33.3 Percentage of participants	25.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Magnesium - High	0 Percentage of participants	0 Percentage of participants	12.5 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Phosphorus - Low	10.0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline International Normalized Ratio - High	0 Percentage of participants	2.6 Percentage of participants	0 Percentage of participants	1.4 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Phosphorus - High	0 Percentage of participants	3.2 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Potassium - High	0 Percentage of participants	3.1 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Sodium - Low	0 Percentage of participants	3.1 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Bilirubin - High	0 Percentage of participants	6.7 Percentage of participants	0 Percentage of participants	4.2 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Protein, Total - Low	0 Percentage of participants	3.3 Percentage of participants	0 Percentage of participants	2.2 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Protein, Total - High	0 Percentage of participants	3.2 Percentage of participants	0 Percentage of participants	2.0 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Prothrombin Time - High	0 Percentage of participants	3.0 Percentage of participants	0 Percentage of participants	1.6 Percentage of participants
Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline Activated Partial Thromboplastin Time - Low	13.3 Percentage of participants	16.2 Percentage of participants	11.8 Percentage of participants	14.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Days 1, 8, and 15

Population: The analysis included a small number of participants who had ECG readings post-treatment because, per the protocol, ECGs were limited to those for whom it was clinically indicated.

Electrocardiogram (ECG) recordings were performed after the participant had been resting in a supine position for at least 10 minutes. ECG parameters included heart rate, PR and QRS durations, and QT and QTcF intervals. Per the protocol, ECG readings post-treatment were limited to those for whom it was clinically indicated. Any of the ECG parameters that were outside of the normal reference range (in the specified direction - low or high) were considered abnormalities. Not every abnormality qualified as an adverse event (AE). An ECG test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment.

Outcome measures

Outcome measures
Measure	Giredestrant 10 mg n=8 Participants Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg n=7 Participants Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg n=4 Participants Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	All Participants, Efficacy: Giredestrant (10, 30, or 100 mg) n=19 Participants This analysis set includes all efficacy-evaluable participants. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Percentage of Participants With Abnormal Electrocardiogram Parameters During Treatment PR Duration - Low	12.5 Percentage of participants	0 Percentage of participants	0 Percentage of participants	5.3 Percentage of participants
Percentage of Participants With Abnormal Electrocardiogram Parameters During Treatment PR Duration - High	0 Percentage of participants	0 Percentage of participants	25.0 Percentage of participants	5.3 Percentage of participants

SECONDARY outcome

Timeframe: Predose on day of surgery (Day 15), or prior to biopsy (Day 14)

Population: The Pharmacokinetics Analysis Population consisted of all participants who received at least one dose of giredestrant and had a measurable concentration at the specific timepoint collected.

Plasma samples were obtained on the day of surgery (Day 15), or prior to biopsy on Day 14.

Outcome measures

Outcome measures
Measure	Giredestrant 10 mg n=16 Participants Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg n=36 Participants Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg n=17 Participants Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	All Participants, Efficacy: Giredestrant (10, 30, or 100 mg) This analysis set includes all efficacy-evaluable participants. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Plasma Concentration of Giredestrant at Steady State by Dose Level	58.8 nanograms per millilitre (ng/mL) Geometric Coefficient of Variation 58.1	130 nanograms per millilitre (ng/mL) Geometric Coefficient of Variation 59.1	441 nanograms per millilitre (ng/mL) Geometric Coefficient of Variation 71.2	—

Adverse Events

Giredestrant 10 mg

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Giredestrant 30 mg

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Giredestrant 100 mg

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

All Participants, Safety: Giredestrant (10, 30, or 100 mg)

Serious events: 4 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Giredestrant 10 mg n=17 participants at risk Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg n=40 participants at risk Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg n=17 participants at risk Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	All Participants, Safety: Giredestrant (10, 30, or 100 mg) n=74 participants at risk This analysis set includes a subset of the safety-evaluable participants who had ECG readings post-treatment because, per the protocol, ECGs were limited to those for whom it was clinically indicated. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Infections and infestations Breast abscess	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Infections and infestations Mastitis	0.00% 0/17 • From Baseline to Day 43	2.5% 1/40 • Number of events 1 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Nervous system disorders Dizziness	0.00% 0/17 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Reproductive system and breast disorders Breast haematoma	0.00% 0/17 • From Baseline to Day 43	2.5% 1/40 • Number of events 1 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43

Other adverse events

Additional Information

Medical Communications

Genentech, Inc.

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but only after the first publication or presentation that involves the overall study. The Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Giredestrant 10 mg n=17 participants at risk Giredestrant 10 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 30 mg n=40 participants at risk Giredestrant 30 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	Giredestrant 100 mg n=17 participants at risk Giredestrant 100 milligrams (mg) was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.	All Participants, Safety: Giredestrant (10, 30, or 100 mg) n=74 participants at risk This analysis set includes a subset of the safety-evaluable participants who had ECG readings post-treatment because, per the protocol, ECGs were limited to those for whom it was clinically indicated. Participants in the three cohorts received giredestrant (10 mg, 30 mg, or 100 mg) that was administered orally once daily up to and including the day of surgery (if allowed per local process) on Day 15. Surgery should have been performed within 24 hours after the last dose of giredestrant. Following surgery, participants had a post-surgery follow-up visit after a period of 28 days.
Psychiatric disorders Insomnia	0.00% 0/17 • From Baseline to Day 43	2.5% 1/40 • Number of events 1 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	2.7% 2/74 • Number of events 2 • From Baseline to Day 43
Reproductive system and breast disorders Breast discomfort	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Reproductive system and breast disorders Breast pain	0.00% 0/17 • From Baseline to Day 43	5.0% 2/40 • Number of events 2 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	4.1% 3/74 • Number of events 3 • From Baseline to Day 43
Injury, poisoning and procedural complications Wound complication	0.00% 0/17 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/17 • From Baseline to Day 43	7.5% 3/40 • Number of events 3 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	5.4% 4/74 • Number of events 4 • From Baseline to Day 43
Musculoskeletal and connective tissue disorders Back pain	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Nervous system disorders Dizziness	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	10.0% 4/40 • Number of events 4 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	8.1% 6/74 • Number of events 6 • From Baseline to Day 43
Nervous system disorders Headache	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	7.5% 3/40 • Number of events 3 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	6.8% 5/74 • Number of events 5 • From Baseline to Day 43
Nervous system disorders Somnolence	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Psychiatric disorders Anxiety	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	5.0% 2/40 • Number of events 3 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	4.1% 3/74 • Number of events 4 • From Baseline to Day 43
Cardiac disorders Bradycardia	0.00% 0/17 • From Baseline to Day 43	5.0% 2/40 • Number of events 2 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	2.7% 2/74 • Number of events 2 • From Baseline to Day 43
Eye disorders Photopsia	0.00% 0/17 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	11.8% 2/17 • Number of events 2 • From Baseline to Day 43	2.7% 2/74 • Number of events 2 • From Baseline to Day 43
Eye disorders Vision blurred	0.00% 0/17 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	11.8% 2/17 • Number of events 2 • From Baseline to Day 43	2.7% 2/74 • Number of events 2 • From Baseline to Day 43
Eye disorders Visual field defect	0.00% 0/17 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Eye disorders Vitreous degeneration	0.00% 0/17 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Gastrointestinal disorders Abdominal pain upper	0.00% 0/17 • From Baseline to Day 43	5.0% 2/40 • Number of events 2 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	2.7% 2/74 • Number of events 2 • From Baseline to Day 43
Gastrointestinal disorders Constipation	0.00% 0/17 • From Baseline to Day 43	5.0% 2/40 • Number of events 2 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	4.1% 3/74 • Number of events 3 • From Baseline to Day 43
Gastrointestinal disorders Diarrhoea	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	2.5% 1/40 • Number of events 1 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	2.7% 2/74 • Number of events 2 • From Baseline to Day 43
Gastrointestinal disorders Dry mouth	0.00% 0/17 • From Baseline to Day 43	5.0% 2/40 • Number of events 2 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	2.7% 2/74 • Number of events 2 • From Baseline to Day 43
Gastrointestinal disorders Dyspepsia	0.00% 0/17 • From Baseline to Day 43	7.5% 3/40 • Number of events 3 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	4.1% 3/74 • Number of events 3 • From Baseline to Day 43
Gastrointestinal disorders Nausea	17.6% 3/17 • Number of events 3 • From Baseline to Day 43	12.5% 5/40 • Number of events 5 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	12.2% 9/74 • Number of events 9 • From Baseline to Day 43
Gastrointestinal disorders Vomiting	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	5.0% 2/40 • Number of events 2 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	5.4% 4/74 • Number of events 4 • From Baseline to Day 43
General disorders Asthenia	0.00% 0/17 • From Baseline to Day 43	7.5% 3/40 • Number of events 3 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	5.4% 4/74 • Number of events 4 • From Baseline to Day 43
General disorders Axillary pain	0.00% 0/17 • From Baseline to Day 43	2.5% 1/40 • Number of events 1 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	2.7% 2/74 • Number of events 2 • From Baseline to Day 43
General disorders Fatigue	11.8% 2/17 • Number of events 2 • From Baseline to Day 43	2.5% 1/40 • Number of events 1 • From Baseline to Day 43	29.4% 5/17 • Number of events 5 • From Baseline to Day 43	10.8% 8/74 • Number of events 8 • From Baseline to Day 43
General disorders Influenza like illness	0.00% 0/17 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
General disorders Malaise	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Infections and infestations Ear infection	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Infections and infestations Gastroenteritis	0.00% 0/17 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Infections and infestations Sinusitis	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Infections and infestations Skin infection	11.8% 2/17 • Number of events 2 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	2.7% 2/74 • Number of events 2 • From Baseline to Day 43
Infections and infestations Subcutaneous abscess	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Infections and infestations Urinary tract infection	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Injury, poisoning and procedural complications Contusion	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Injury, poisoning and procedural complications Procedural pain	11.8% 2/17 • Number of events 2 • From Baseline to Day 43	2.5% 1/40 • Number of events 1 • From Baseline to Day 43	17.6% 3/17 • Number of events 3 • From Baseline to Day 43	8.1% 6/74 • Number of events 6 • From Baseline to Day 43
Injury, poisoning and procedural complications Product dose omission in error	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	2.7% 2/74 • Number of events 2 • From Baseline to Day 43
Injury, poisoning and procedural complications Seroma	11.8% 2/17 • Number of events 2 • From Baseline to Day 43	2.5% 1/40 • Number of events 1 • From Baseline to Day 43	11.8% 2/17 • Number of events 2 • From Baseline to Day 43	6.8% 5/74 • Number of events 5 • From Baseline to Day 43
Skin and subcutaneous tissue disorders Dry skin	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Skin and subcutaneous tissue disorders Hyperhidrosis	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	0.00% 0/40 • From Baseline to Day 43	0.00% 0/17 • From Baseline to Day 43	1.4% 1/74 • Number of events 1 • From Baseline to Day 43
Vascular disorders Hot flush	11.8% 2/17 • Number of events 2 • From Baseline to Day 43	7.5% 3/40 • Number of events 3 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	8.1% 6/74 • Number of events 6 • From Baseline to Day 43
Vascular disorders Hypertension	0.00% 0/17 • From Baseline to Day 43	2.5% 1/40 • Number of events 2 • From Baseline to Day 43	5.9% 1/17 • Number of events 1 • From Baseline to Day 43	2.7% 2/74 • Number of events 3 • From Baseline to Day 43