A Study Evaluating the Efficacy and Safety of Giredestrant Compared With Physician's Choice of Endocrine Monotherapy in Participants With Previously Treated Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (acelERA Breast Cancer)

• ClinicalTrials.gov Identifier: NCT04576455
• Recruitment Status: Active, not recruiting
• First Posted: October 6, 2020
• Results First Posted: March 10, 2023
• Last Update Posted: February 28, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer
• Interventions: Drug: Giredestrant; Drug: Fulvestrant or an Aromatase Inhibitor (Physician Choice); Drug: LHRH Agonist
• Enrollment: 303

Participant Flow

Recruitment Details	Participants were enrolled in this study at 85 investigational sites in the following countries: Argentina, Australia, Brazil, China, Germany, Israel, Poland, Republic of Korea, Russian Federation, Singapore, South Africa, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, and the United States from 27 November 2020 to 27 October 2021. The study is ongoing.
Pre-assignment Details	A total of 303 participants were enrolled in this study, of which one participant randomized to giredestrant arm received fulvestrant in error & was grouped in the physician's choice of endocrine monotherapy (PCET) arm for safety analysis.

Arm/Group Title	Giredestrant	Physician's Choice of Endocrine Monotherapy
Arm/Group Description	Participants received giredestrant, 30 milligrams (mg), orally (PO), once daily (QD), on Days 1-28 (and luteinizing hormone-releasing hormone [LHRH] agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Participants received PECT (fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
Period Title: Overall Study
Started	151	152
Safety-Evaluable Population [1]	150 [2]	152 [3]
Completed	0	0
Not Completed	151	152
Reason Not Completed
Ongoing in the Study	122	135
Death	18	12
Lost to Follow-up	1	0
Withdrawal by Subject	10	5
[1] Safety-Evaluable Population included all participants who received at least one dose of the study treatment (giredestrant or PCET).; [2] 1 participant randomized to the giredestrant arm received fulvestrant in error thus was counted in PCET arm for safety analysis.; [3] 1 participant randomized to the giredestrant arm received fulvestrant in error thus counted in this arm for safety analysis and 1 participant randomized to this arm discontinued the study before receiving any study drug.

Baseline Characteristics

Arm/Group Title		Giredestrant	Physician's Choice of Endocrine Monotherapy	Total
Arm/Group Description		Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Participants received PECT (fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.	Total of all reporting groups
Overall Number of Baseline Participants		151	152	303
Baseline Analysis Population Description		Full Analysis Set (FAS) included all participants assigned to treatment groups as randomized by the interactive voice or web-based response system (IxRS).
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	151 participants	152 participants	303 participants
		59.5 (12.4)	57.8 (10.7)	58.6 (11.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	151 participants	152 participants	303 participants
	Female	151 100.0%	151 99.3%	302 99.7%
	Male	0 0.0%	1 0.7%	1 0.3%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	151 participants	152 participants	303 participants
	Hispanic or Latino	23 15.2%	20 13.2%	43 14.2%
	Not Hispanic or Latino	128 84.8%	132 86.8%	260 85.8%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	151 participants	152 participants	303 participants
	American Indian or Alaska Native	1 0.7%	0 0.0%	1 0.3%
	Asian	58 38.4%	66 43.4%	124 40.9%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	2 1.3%	2 1.3%	4 1.3%
	White	89 58.9%	81 53.3%	170 56.1%
	More than one race	0 0.0%	1 0.7%	1 0.3%
	Unknown or Not Reported	1 0.7%	2 1.3%	3 1.0%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS), as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Description	PFS was defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.
Time Frame	From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to a clinical cutoff of 15 months)

Outcome Measure Data

Analysis Population Description

FAS included all participants assigned to treatment groups as randomized by the IxRS. Participants without the occurrence of disease progression or death as of the clinical cutoff were censored at the time of the last tumor assessment prior to the clinical cutoff or at the time of randomization plus 1 day for those without post-baseline assessment.

Arm/Group Title	Giredestrant	Physician's Choice of Endocrine Monotherapy
Arm/Group Description:	Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Participants received PECT (fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
Overall Number of Participants Analyzed	151	152
Median (95% Confidence Interval); Unit of Measure: months
	5.55; (4.93 to 7.36)	5.36; (3.71 to 5.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Giredestrant, Physician's Choice of Endocrine Monotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1757
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.60 to 1.10
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is defined as the time from randomization to death from any cause.
Time Frame	From randomization to death from any cause (up to approximately 36 months)

Outcome Measure Data Not Reported

3. Secondary Outcome

Title	Objective Response Rate, as Determined by the Investigator According to RECIST v1.1
Description	The objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart. Per RECIST v1.1, CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to <10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
Time Frame	From randomization until disease progression or death (up to approximately 36 months)

Outcome Measure Data Not Reported

4. Secondary Outcome

Title	Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1
Description	DOR is defined as the time from the first occurrence of a documented objective response to disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first). Objective response rate is defined as the percentage of participants with a CR or PR on two consecutive occasions at least 4 weeks apart. Per RECIST v1.1, CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to <10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.
Time Frame	From first occurrence of documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 36 months)

Outcome Measure Data Not Reported

5. Secondary Outcome

Title	Clinical Benefit Rate, as Determined by the Investigator According to RECIST v1.1
Description	The clinical benefit rate is defined as the percentage of participants with stable disease for ≥24 weeks or a CR or PR. Per RECIST v1.1, CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to <10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
Time Frame	From randomization until disease progression or death (up to approximately 36 months)

Outcome Measure Data Not Reported

6. Secondary Outcome

Title	Investigator-Assessed PFS, in Subgroups Categorized by Estrogen Receptor 1 (ESR1) Mutation Status
Description	PFS was defined as the time from randomization to the first occurrence of disease progression determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first). Disease progression was defined as ≥20% increase in in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. Investigator-assessed PFS was analyzed in subgroups categorized by baseline ESR1 mutation status (i.e., with or without ESR1 mutation at baseline) from plasma circulating tumor deoxyribonucleic acid (ctDNA).
Time Frame	From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to a clinical cutoff of 15 months)

Outcome Measure Data

Analysis Population Description

ctDNA-evaluable population included all FAS participants with evaluable plasma ctDNA at baseline. Number analyzed is the number of participants with data available for analysis at the specified time point. Participants without the occurrence of disease progression or death as of the clinical cutoff were censored at the time of last tumor assessment prior to the clinical cutoff or at the time of randomization plus 1 day for those without post-baseline assessment.

Arm/Group Title		Giredestrant	Physician's Choice of Endocrine Monotherapy
Arm/Group Description:		Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Participants received PECT (fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product. In addition, premenopausal/perimenopausal participants and male participants received a LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day treatment cycle until disease progression or unacceptable toxicity, whichever occurs first.
Overall Number of Participants Analyzed		117	115
Median (95% Confidence Interval); Unit of Measure: months
PFS by ESR1 Mutation Detected at Baseline	Number Analyzed	51 participants	39 participants
		5.32; (3.61 to 5.59)	3.48; (1.81 to 3.81)
PFS by ESR1 Mutation Not Detected at Baseline	Number Analyzed	66 participants	76 participants
		7.20; (5.36 to 11.17)	6.60 [1]; (5.32 to NA)

[1]

The upper limit of 95% confidence interval (CI) was not estimable due to insufficient data.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Giredestrant, Physician's Choice of Endocrine Monotherapy
	Comments	This statistical analysis is done for PFS by ESR1 mutation detected at baseline
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0237
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; 0.33 to 0.93
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Giredestrant, Physician's Choice of Endocrine Monotherapy
	Comments	This statistical analysis is done for PFS by ESR1 Mutation not detected at baseline
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9647
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.64 to 1.60
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Time to Deterioration (TTD) in Pain Severity
Description	TTD in pain severity is defined as time to first documented ≥2-point increase from Baseline in the "Worst Pain" item from the Brief Pain Inventory-Short Form (BPI-SF) Questionnaire. The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 10-point numeric rating scale, with 0="No pain", "No interference" to 10="Pain as bad as you can imagine", "Highest imaginable interference". A lower score indicates improvement.
Time Frame	From Baseline until treatment discontinuation (up to approximately 36 months)

Outcome Measure Data Not Reported

8. Secondary Outcome

Title	TTD in Pain Presence and Interference, Defined as Time to First Documented ≥10-Point Increase From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Linearly Transformed Pain Scale Score
Description	EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health and quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) with a recall period of the previous week. The functioning and symptoms items are scored on a 4-point scale that ranges from 1=not at all to 4=very much. The Pain scale is scored on a 4-point scale (1=Not at All to 4=Very Much). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate worse pain symptoms.
Time Frame	From Baseline until treatment discontinuation (up to approximately 36 months)

Outcome Measure Data Not Reported

9. Secondary Outcome

Title	TTD in Physical Functioning (PF)
Description	TTD in PF is defined as the time to first documented ≥10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed PF scale score. EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health and quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) with a recall period of the previous week. The PF scale has 5 questions about participants' physical functioning and is scored on a 4-point scale (1=Not at All to 4=Very Much). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a higher response level (better physical function).
Time Frame	From Baseline until treatment discontinuation (up to approximately 36 months)

Outcome Measure Data Not Reported

10. Secondary Outcome

Title	TTD in Role Functioning (RF)
Description	TTD in RF is defined as the time to first documented ≥10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed RF scale score. EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions that assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health and quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) with a recall period of the previous week. The RF scale is scored on a 4-point scale (1=Not at All to 4=Very Much). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate better functioning/support.
Time Frame	From Baseline until treatment discontinuation (up to approximately 36 months)

Outcome Measure Data Not Reported

11. Secondary Outcome

Title	TTD in Global Health Status and Quality of Life (GHS/QoL)
Description	TTD in GHS/QoL is defined as the time to first documented ≥10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed GHS/QoL scale score. EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions that assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health and quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) with a recall period of the previous week. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a better QoL.
Time Frame	From Baseline until treatment discontinuation (up to approximately 36 months)

Outcome Measure Data Not Reported

12. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs), Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
Description	An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; any new disease or exacerbation of an existing disease; recurrence of an intermittent medical condition; any deterioration in a laboratory value or other clinical test; AEs that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment.
Time Frame	From Baseline until 30 days after final dose of study drug (up to approximately 36 months)

Outcome Measure Data Not Reported

13. Secondary Outcome

Title	Number of Participants With Vital Sign Abnormalities Over the Course of the Study
Description	Vital signs include respiratory rate, pulse rate, systolic and diastolic blood pressure while the patient is in a seated position, and temperature.
Time Frame	Assessed at Baseline and predose on Day 1 of every cycle (1 cycle is 28 days) until 30 days after the final dose of study drug (up to approximately 36 months)

Outcome Measure Data Not Reported

14. Secondary Outcome

Title	Number of Participants With Clinical Laboratory Test Abnormalities for Hematology Parameters Over the Course of the Study
Description	Hematology parameters include white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, other cells).
Time Frame	Assessed at Baseline and predose on Day 1 of every cycle (1 cycle is 28 days) until 30 days after the final dose of study drug (up to approximately 36 months)

Outcome Measure Data Not Reported

15. Secondary Outcome

Title	Number of Participants With Clinical Laboratory Test Abnormalities for Biochemistry Parameters Over the Course of the Study
Description	Biochemistry parameters include bicarbonate or total carbon dioxide, sodium, potassium, chloride, glucose, blood urea nitrogen (BUN) or urea, creatinine, total protein, albumin, phosphate, calcium, total and direct bilirubin, alkaline phosphatase level test (ALP), Alanine transaminase (ALT), aspartate aminotransferase (AST), urate, and lactate dehydrogenase (LDH).
Time Frame	Assessed at Baseline and predose on Day 1 of every cycle (1 cycle is 28 days) until 30 days after the final dose of study drug (up to approximately 36 months)

Outcome Measure Data Not Reported

16. Secondary Outcome

Title	Plasma Concentration of Giredestrant at Specified Timepoints
Description	[Not Specified]
Time Frame	Predose and postdose on Day 1 of Cycles 1 and 2, predose on Day 1 of Cycles 3, 5, 7, 9, 11, 13, and 15 (1 cycle is 28 days), and 30 days after final dose of study drug (up to approximately 36 months)

Outcome Measure Data Not Reported

Adverse Events

Time Frame	From signing of informed consent form until primary completion date (up to 15 months)
Adverse Event Reporting Description	All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Arm/Group Title	Giredestrant		Physician Choice of Endocrine Monotherapy
Arm/Group Description	Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.		Participants received PECT (fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
All-Cause Mortality
	Giredestrant		Physician Choice of Endocrine Monotherapy
	Affected / at Risk (%)		Affected / at Risk (%)
Total	18/151 (11.92%)		12/152 (7.89%)
Serious Adverse Events
	Giredestrant		Physician Choice of Endocrine Monotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/150 (9.33%)		12/152 (7.89%)
Blood and lymphatic system disorders
Anaemia † 1	1/150 (0.67%)	1	1/152 (0.66%)	1
Cardiac disorders
Cardiac failure † 1	1/150 (0.67%)	1	0/152 (0.00%)	0
Cardiac failure acute † 1	1/150 (0.67%)	1	0/152 (0.00%)	0
Myocardial infarction † 1	1/150 (0.67%)	1	0/152 (0.00%)	0
Pericardial effusion † 1	0/150 (0.00%)	0	1/152 (0.66%)	1
Gastrointestinal disorders
Diarrhoea † 1	1/150 (0.67%)	1	0/152 (0.00%)	0
Vomiting † 1	2/150 (1.33%)	2	0/152 (0.00%)	0
General disorders
Asthenia † 1	0/150 (0.00%)	0	1/152 (0.66%)	1
Infections and infestations
Arthritis bacterial † 1	0/150 (0.00%)	0	1/152 (0.66%)	1
COVID-19 † 1	0/150 (0.00%)	0	2/152 (1.32%)	2
COVID-19 pneumonia † 1	0/150 (0.00%)	0	1/152 (0.66%)	1
Viral infection † 1	1/150 (0.67%)	1	0/152 (0.00%)	0
Injury, poisoning and procedural complications
Femur fracture † 1	1/150 (0.67%)	1	0/152 (0.00%)	0
Post procedural haemorrhage † 1	1/150 (0.67%)	1	0/152 (0.00%)	0
Thoracic vertebral fracture † 1	0/150 (0.00%)	0	1/152 (0.66%)	1
Vascular graft stenosis † 1	1/150 (0.67%)	2	0/152 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	1/150 (0.67%)	1	0/152 (0.00%)	0
Aspartate aminotransferase increased † 1	1/150 (0.67%)	1	0/152 (0.00%)	0
Blood bilirubin increased † 1	1/150 (0.67%)	1	0/152 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/150 (0.67%)	1	0/152 (0.00%)	0
Bone pain † 1	1/150 (0.67%)	1	1/152 (0.66%)	1
Nervous system disorders
Cerebral infarction † 1	1/150 (0.67%)	1	0/152 (0.00%)	0
Epilepsy † 1	0/150 (0.00%)	0	1/152 (0.66%)	1
Ischaemic stroke † 1	2/150 (1.33%)	2	0/152 (0.00%)	0
Partial seizures † 1	0/150 (0.00%)	0	1/152 (0.66%)	1
Renal and urinary disorders
Renal failure † 1	0/150 (0.00%)	0	1/152 (0.66%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	1/150 (0.67%)	1	0/152 (0.00%)	0
Pleural effusion † 1	0/150 (0.00%)	0	1/152 (0.66%)	2
Pneumonitis † 1	0/150 (0.00%)	0	1/152 (0.66%)	1
Pulmonary embolism † 1	0/150 (0.00%)	0	1/152 (0.66%)	1
1 Term from vocabulary, MedDRA version 24.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Giredestrant		Physician Choice of Endocrine Monotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	94/150 (62.67%)		66/152 (43.42%)
Blood and lymphatic system disorders
Anaemia † 1	14/150 (9.33%)	14	8/152 (5.26%)	9
Gastrointestinal disorders
Constipation † 1	9/150 (6.00%)	9	11/152 (7.24%)	13
Diarrhoea † 1	13/150 (8.67%)	16	6/152 (3.95%)	11
Nausea † 1	15/150 (10.00%)	22	11/152 (7.24%)	12
Vomiting † 1	11/150 (7.33%)	13	2/152 (1.32%)	5
General disorders
Asthenia † 1	10/150 (6.67%)	10	5/152 (3.29%)	5
Chest pain † 1	8/150 (5.33%)	8	1/152 (0.66%)	1
Fatigue † 1	11/150 (7.33%)	12	6/152 (3.95%)	6
Injury, poisoning and procedural complications
Product dose omission in error † 1	11/150 (7.33%)	25	0/152 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	16/150 (10.67%)	20	11/152 (7.24%)	11
Aspartate aminotransferase increased † 1	21/150 (14.00%)	24	13/152 (8.55%)	15
Blood bilirubin increased † 1	8/150 (5.33%)	11	1/152 (0.66%)	2
Metabolism and nutrition disorders
Decreased appetite † 1	8/150 (5.33%)	8	3/152 (1.97%)	3
Musculoskeletal and connective tissue disorders
Arthralgia † 1	17/150 (11.33%)	19	12/152 (7.89%)	12
Back pain † 1	8/150 (5.33%)	9	4/152 (2.63%)	4
Bone pain † 1	8/150 (5.33%)	9	9/152 (5.92%)	9
Nervous system disorders
Dizziness † 1	9/150 (6.00%)	10	7/152 (4.61%)	7
Headache † 1	11/150 (7.33%)	14	13/152 (8.55%)	22
Vascular disorders
Hypertension † 1	9/150 (6.00%)	10	3/152 (1.97%)	4
1 Term from vocabulary, MedDRA version 24.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800-821-8590
• EMail: genentech@druginfo.com

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT04576455
• Other Study ID Numbers: WO42312; 2020-001984-10 ( EudraCT Number )
• First Submitted: September 30, 2020
• First Posted: October 6, 2020
• Results First Submitted: February 13, 2023
• Results First Posted: March 10, 2023
• Last Update Posted: February 28, 2024