AMEERA-4: Phase 2 Window Study of SAR439859 (Amcenestrant) Versus Letrozole in Post-menopausal Patients With ER+, HER2- Pre-operative Post-menopausal Primary Breast Cancer

• Sponsor: Sanofi (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04191382
• Collaborator: (none)
• Enrollment: 105
• Locations: 32
• Arms: 3
• Actual Duration (Months): 15.7
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Primary Objective:

To determine whether amcenestrant given at 2 different doses improved the antiproliferative activity when compared to letrozole.

Secondary Objectives:

• To assess the proportion of participants with a relative decrease from Baseline in percentage of positive tumor cells tested by immunohistochemistry greater than or equal to (>=) 50 percent (%) (Ki67 >=50%) in the three treatment arms.

• To assess estrogen receptor (ER) degradation in biopsies in participants in the three treatment arms.

• To assess safety in the three treatment arms.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Amcenestrant (SAR439859); Drug: Letrozole	Phase 2

Detailed Description

Duration of the study, per participant, would include screening period of up to 14 days before randomization, treatment period of 14 days and post-treatment safety follow-up period of 30±7 days after last investigational medicinal product (IMP) intake.

Study Design

• Study Type: Interventional
• Actual Enrollment: 105 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase 2 Window Study of Two Dose Levels of Amcenestrant [SAR439859] (SERD) Versus Letrozole in Newly Diagnosed Pre-operative Post-menopausal Patients With ER Positive, HER2 Negative Primary Breast Cancer
• Actual Study Start Date: Feb 4, 2020
• Actual Primary Completion Date: Apr 30, 2021
• Actual Study Completion Date: May 28, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Amcenestrant 400 mg Participants received 4 capsules of 100 milligrams (mg) of amcenestrant once daily (QD) from Day 1 to Day 14.	Drug: Amcenestrant (SAR439859); Pharmaceutical form: Capsules, Route of administration: Oral
Experimental: Amcenestrant 200 mg Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.	Drug: Amcenestrant (SAR439859); Pharmaceutical form: Capsules, Route of administration: Oral
Active Comparator: Letrozole 2.5 mg Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.	Drug: Letrozole; Pharmaceutical form: Tablets, Route of administration: Oral

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Ki67 Level at Day 15 [Baseline, Day 15]

   Tumor tissue collected through a core-cut biopsy at Baseline and Day 15 was used to determine Ki67 expression. Ki67 expression was defined as the percentage of positive tumor cells assessed by central reading. Ki67 percent change from Baseline for a given participant was defined as 100*(Ki67pre - Ki67post) / Ki67pre, where Ki67pre and Ki67post were pre-treatment and post-treatment Ki67 value of the participant. Adjusted geometric least square (LS) means and 95 percentage (%) confidence interval (CI) for the percent change were obtained from analysis of covariance (ANCOVA) model of the log proportional change i.e., log (Ki67post/ki67pre) with treatment and log-Ki67pre as fixed effect and converted by antilog transformation.

Secondary Outcome Measures

1. Percentage of Participants With Percent Change From Baseline in Ki67 Greater Than or Equal to (>=) 50 Percent at Day 15 [Baseline, Day 15]

   Tumor tissue collected through a core-cut biopsy at Baseline and Day 15 was used to determine Ki67 expression. Ki67 expression was defined as the percentage of positive tumor cells assessed by central reading. Ki67 percent change from Baseline for a given participant was defined as 100*(Ki67pre - Ki67post) / Ki67pre, where Ki67pre and Ki67post were pre-treatment and post-treatment Ki67 value of the participant.

2. Change From Baseline in Estrogen Receptor (ER) Expression as Measured by H-Score at Day 15 [Baseline, Day 15]

   Change from Baseline in ER expression was measured by H-Score. The H-score was calculated as the sum of the percent of cells staining positive (0 to 100) multiplied staining intensity level from 0 to 3 (0=none, 1=low, 2=moderate, 3=high). Total ER expression H-score ranged from 0 to 300, where higher score indicated stronger ER expression. Change from Baseline in H-Score equals H-scorepost minus H-scorepre; where H-scorepost and H-scorepre denoted post-treatment and pre-treatment H-scores, respectively. LS-means and 95% CI were obtained from an ANCOVA model for change from baseline with treatment and baseline as fixed effect.

3. Number of Participants With Abnormalities: Hematological Parameters [From first dose of study drug up to Day 14]

   Hematology parameters covered by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) and included: Hemoglobin, Lymphocyte, Neutrophils, Leukocytes (white blood cells), Anemia, Platelets, Eosinophils, and international normalized ratio (INR). An NCI-CTCAE Grades 1 to 5 were described as: Grade 1-Mild; asymptomatic/mild symptoms; Grade 2-Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental daily activities. Grade 3-Severe/medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; Grade 4-Life-threatening consequences; Grade 5-Death. Data for 'All Grades' were reported in this outcome measure.

4. Number of Participants With Abnormalities: Clinical Chemistry [From first dose of study drug up to Day 14]

   Clinical chemistry laboratory parameters covered by NCI-CTCAE and included: Glucose, Potassium, Sodium, Creatinine. An NCI-CTCAE Grades 1 to 5 were described as: Grade 1-Mild; asymptomatic or mild symptoms; Grade 2- Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental daily activities; Grade 3-Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; Grade 4-Life-threatening consequences; Grade 5-Death. Data for 'All Grades' were reported in this outcome measure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion criteria :

• Histological or cytological proven diagnosis of invasive breast adenocarcinoma.

• Localized breast cancer eligible for upfront breast conservative surgery or upfront mastectomy: Stage I, Stage II or operable Stage III (excluded T4) as defined in American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th edition 2017.

• Postmenopausal women as defined by one of the following:

• Spontaneous cessation of menses greater than (>) 12 months.

• or who had received hormonal replacement therapy but had discontinued the treatment and had follicle stimulating hormone (FSH) level in the postmenopausal range.

• or with status post bilateral surgical oophorectomy.

• or post bilateral ovarian ablation through pelvic radiotherapy.

• Breast tumor size of at least 10 millimeters (mm) in greatest dimension measured by ultrasound.

• Primary tumor had to be positive for Estrogen Receptors (ER+) and negative for HER2 (HER2-) receptor by immunohistochemistry.

• Ki67 level of at least 15% at diagnosis from immunohistochemistry of the tumor.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

Exclusion criteria:

• Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of SAR439859 or letrozole.

• Participants unable to swallow normally and to take capsules or tablets.

• Participants with known active hepatitis A, B, C infection; or hepatic cirrhosis.

• Participant with any other cancer; adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or any other cancer from which the participant had been disease free for >3 years were allowed.

• Evidence of metastatic spread by standard assessment according to local practice.

• Treatment with strong Cytochrome P450 3A (CYP3A) inducers or drugs that had the potential to inhibit uridine diphosphate glucuronosyltransferase (UGT) within 2 weeks before first study treatment administration or 5 elimination half-lives whichever was longest.

• Treatment with drugs that were sensitive substrates of P-glycoprotein (P-gp) or of breast cancer resistance protein (BCRP) within 2 weeks before first study treatment administration or 5 elimination half-lives whichever was longer.

• Use of any investigational agent within 4 weeks prior to randomization.

• Recent use of hormone replacement therapy (last dose less than or equal to [<=] 30 days prior to randomization).

• Prior anti-cancer treatment was not allowed unless it was then completed at least 1 year prior to inclusion into this trial.

• Previous systemic or local treatment for the new primary breast cancer currently under investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments).

• Inadequate hematological or renal function.

• Prothrombin time/international normalized ratio (INR) >1.5 * upper limit of normal (ULN) or outside therapeutic range if received anticoagulation that would have had affected the prothrombin time/INR.

• Any of the following abnormal liver function test results: Aspartate aminotransferase

1.5 * ULN; Alanine aminotransferase >1.5 * ULN; Total bilirubin >1.5 * ULN.

• Participants were employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals.

• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 8400014	Tucson	Arizona	United States	85724
2	Investigational Site Number 8400010	Los Angeles	California	United States	90095
3	Investigational Site Number 8400018	Fort Wayne	Indiana	United States	46804
4	Investigational Site Number 8400005	Lincoln	Nebraska	United States	68506
5	Investigational Site Number 8400016	Winston-Salem	North Carolina	United States	27157
6	Investigational Site Number 8400012	Tacoma	Washington	United States	98405
7	Investigational Site Number 0560001	Leuven		Belgium	3000
8	Investigational Site Number 0560002	Namur		Belgium	5000
9	Investigational Site Number 2500001	Nantes		France	44093
10	Investigational Site Number 2500004	Paris		France	75010
11	Investigational Site Number 2500002	Saint Cloud		France	92210
12	Investigational Site Number 2500003	Toulouse Cedex 9		France	31059
13	Investigational Site Number 3800004	Meldola		Italy	47014
14	Investigational Site Number 3800002	Milano		Italy	20132
15	Investigational Site Number 3800001	Milano		Italy	20141
16	Investigational Site Number 3920002	Osaka-Shi		Japan
17	Investigational Site Number 3920003	Sapporo-Shi		Japan
18	Investigational Site Number 3920001	Yokohama-Shi		Japan
19	Investigational Site Number 8400007	Hato Rey		Puerto Rico	00917
20	Investigational Site Number 6430006	Moscow		Russian Federation	117186
21	Investigational Site Number 6430004	Moscow		Russian Federation	119991
22	Investigational Site Number 6430002	Saint -Petersburg		Russian Federation	197758
23	Investigational Site Number 6430003	Saint-Petersburg		Russian Federation	194156
24	Investigational Site Number 6430007	St.Petersburg		Russian Federation	195271
25	Investigational Site Number 7240005	Barcelona		Spain	08003
26	Investigational Site Number 7240003	Córdoba		Spain	14004
27	Investigational Site Number 7240001	Madrid		Spain	28041
28	Investigational Site Number 7240002	Valencia / Valencia		Spain	46010
29	Investigational Site Number 8040004	Kharkiv		Ukraine	61166
30	Investigational Site Number 8040001	Uzhgorod		Ukraine	88000
31	Investigational Site Number 8040002	Vinnytsia		Ukraine	21029
32	Investigational Site Number 8040005	Zaporizhzhya		Ukraine	69040

Sponsors and Collaborators

• Sanofi

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

• Study Protocol - Feb 4, 2021
• Statistical Analysis Plan - Jun 9, 2021

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT04191382
• Other Study ID Numbers: ACT16106; 2019-002015-26; U1111-1228-9473
• First Posted: Dec 9, 2019
• Last Update Posted: Jun 29, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Breast Neoplasms; Letrozole

Study Results

Participant Flow

Recruitment Details	The study was conducted at 32 active sites in 8 countries. A total of 135 participants were screened from 04-February-2020 to 21-April-2021, of which 30 participants were screen failures mainly due to selection criteria not met.
Pre-assignment Detail	A total of 105 participants with early breast cancer were randomized in 1:1:1 ratio to receive treatment with amcenestrant 400 milligrams (mg), amcenestrant 200 mg, or letrozole 2.5 mg.

Arm/Group Title	Amcenestrant 400 mg	Amcenestrant 200 mg	Letrozole 2.5 mg
Arm/Group Description	Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14.	Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.	Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
Period Title: Overall Study
STARTED	34	36	35
Treated	33	36	35
COMPLETED	33	36	35
NOT COMPLETED	1	0	0

Baseline Characteristics

Arm/Group Title	Amcenestrant 400 mg	Amcenestrant 200 mg	Letrozole 2.5 mg	Total Title
Arm/Group Description	Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14.	Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.	Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
Overall Participants	34	36	35	105
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.4 (8.6)	63.4 (8.4)	63.7 (8.5)	63.2 (8.4)
Sex: Female, Male (Count of Participants)
Female	34 100%	36 100%	35 100%	105 100%
Male	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	2 5.9%	3 8.3%	5 14.3%	10 9.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 2.9%	0 0%	0 0%	1 1%
White	23 67.6%	24 66.7%	25 71.4%	72 68.6%
More than one race	0 0%	1 2.8%	1 2.9%	2 1.9%
Unknown or Not Reported	8 23.5%	8 22.2%	4 11.4%	20 19%
Ki67 expression at Baseline (percentage of positive tumor cells) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of positive tumor cells]	33.8 (16.3)	31.2 (14.3)	32.6 (18.5)	32.5 (16.3)

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Ki67 Level at Day 15
Description	Tumor tissue collected through a core-cut biopsy at Baseline and Day 15 was used to determine Ki67 expression. Ki67 expression was defined as the percentage of positive tumor cells assessed by central reading. Ki67 percent change from Baseline for a given participant was defined as 100*(Ki67pre - Ki67post) / Ki67pre, where Ki67pre and Ki67post were pre-treatment and post-treatment Ki67 value of the participant. Adjusted geometric least square (LS) means and 95 percentage (%) confidence interval (CI) for the percent change were obtained from analysis of covariance (ANCOVA) model of the log proportional change i.e., log (Ki67post/ki67pre) with treatment and log-Ki67pre as fixed effect and converted by antilog transformation.
Time Frame	Baseline, Day 15

Outcome Measure Data

Analysis Population Description

Analysis was performed on modified intent-to-treat (mITT) population that included all enrolled participants for whom there was a confirmation of successful allocation of a randomization number by IRT, who had taken at least one study drug, and who had both Baseline and post treatment available biopsies with Ki67 values.

Arm/Group Title	Amcenestrant 400 mg	Amcenestrant 200 mg	Letrozole 2.5 mg
Arm/Group Description	Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14.	Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.	Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
Measure Participants	31	35	29
Geometric Least Squares Mean (95% Confidence Interval) [percent change]	75.9	68.2	77.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amcenestrant 400 mg, Letrozole 2.5 mg
	Comments	Geometric LS-means ratio of proportional change was the ratio of geometric LS-means of the proportional change between groups (Amcenestrant 400 mg versus Letrozole 2.5 mg).
	Type of Statistical Test	Other
	Comments	Other descriptive analysis
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Means
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Amcenestrant 200 mg, Letrozole 2.5 mg
	Comments	Geometric LS-means ratio of proportional change was the ratio of geometric LS-means of the proportional change between groups (Amcenestrant 200 mg versus Letrozole 2.5 mg).
	Type of Statistical Test	Other
	Comments	Other descriptive analysis
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Means
	Estimated Value	1.42
	Confidence Interval	(2-Sided) 95%; 0.95 to 2.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Percent Change From Baseline in Ki67 Greater Than or Equal to (>=) 50 Percent at Day 15
Description	Tumor tissue collected through a core-cut biopsy at Baseline and Day 15 was used to determine Ki67 expression. Ki67 expression was defined as the percentage of positive tumor cells assessed by central reading. Ki67 percent change from Baseline for a given participant was defined as 100*(Ki67pre - Ki67post) / Ki67pre, where Ki67pre and Ki67post were pre-treatment and post-treatment Ki67 value of the participant.
Time Frame	Baseline, Day 15

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population.

Arm/Group Title	Amcenestrant 400 mg	Amcenestrant 200 mg	Letrozole 2.5 mg
Arm/Group Description	Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14.	Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.	Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
Measure Participants	31	35	29
Number (95% Confidence Interval) [percentage of participants]	74.2 218.2%	68.6 190.6%	89.7 256.3%

3. Secondary Outcome

Title	Change From Baseline in Estrogen Receptor (ER) Expression as Measured by H-Score at Day 15
Description	Change from Baseline in ER expression was measured by H-Score. The H-score was calculated as the sum of the percent of cells staining positive (0 to 100) multiplied staining intensity level from 0 to 3 (0=none, 1=low, 2=moderate, 3=high). Total ER expression H-score ranged from 0 to 300, where higher score indicated stronger ER expression. Change from Baseline in H-Score equals H-scorepost minus H-scorepre; where H-scorepost and H-scorepre denoted post-treatment and pre-treatment H-scores, respectively. LS-means and 95% CI were obtained from an ANCOVA model for change from baseline with treatment and baseline as fixed effect.
Time Frame	Baseline, Day 15

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population. Here, 'overall number of participants analyzed' signifies participants with available data for this outcome measure.

Arm/Group Title	Amcenestrant 400 mg	Amcenestrant 200 mg	Letrozole 2.5 mg
Arm/Group Description	Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14.	Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.	Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
Measure Participants	28	32	28
Least Squares Mean (95% Confidence Interval) [score on a scale]	-176.7	-202.9	-32.5

4. Secondary Outcome

Title	Number of Participants With Abnormalities: Hematological Parameters
Description	Hematology parameters covered by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) and included: Hemoglobin, Lymphocyte, Neutrophils, Leukocytes (white blood cells), Anemia, Platelets, Eosinophils, and international normalized ratio (INR). An NCI-CTCAE Grades 1 to 5 were described as: Grade 1-Mild; asymptomatic/mild symptoms; Grade 2-Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental daily activities. Grade 3-Severe/medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; Grade 4-Life-threatening consequences; Grade 5-Death. Data for 'All Grades' were reported in this outcome measure.
Time Frame	From first dose of study drug up to Day 14

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population that included all participants who were randomly assigned to study drug and who took at least 1 dose of study drug. Here, 'Number analyzed' signifies participants with available data for each specified category for this outcome measure.

Arm/Group Title	Amcenestrant 400 mg	Amcenestrant 200 mg	Letrozole 2.5 mg
Arm/Group Description	Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14.	Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.	Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
Measure Participants	33	36	35
White blood cell decreased	5 14.7%	6 16.7%	3 8.6%
Neutrophil count decreased	1 2.9%	0 0%	1 2.9%
Anemia (hemoglobin decreased)	6 17.6%	4 11.1%	1 2.9%
Hemoglobin increased	0 0%	0 0%	0 0%
Platelet count decreased	1 2.9%	1 2.8%	0 0%
Lymphocyte count decreased	1 2.9%	3 8.3%	1 2.9%
INR increased	0 0%	0 0%	0 0%
Eosinophilia (eosinophils increased)	2 5.9%	1 2.8%	1 2.9%

5. Secondary Outcome

Title	Number of Participants With Abnormalities: Clinical Chemistry
Description	Clinical chemistry laboratory parameters covered by NCI-CTCAE and included: Glucose, Potassium, Sodium, Creatinine. An NCI-CTCAE Grades 1 to 5 were described as: Grade 1-Mild; asymptomatic or mild symptoms; Grade 2- Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental daily activities; Grade 3-Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; Grade 4-Life-threatening consequences; Grade 5-Death. Data for 'All Grades' were reported in this outcome measure.
Time Frame	From first dose of study drug up to Day 14

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. Here, 'Number analyzed' signifies participants with available data for each specified category for this outcome measure.

Arm/Group Title	Amcenestrant 400 mg	Amcenestrant 200 mg	Letrozole 2.5 mg
Arm/Group Description	Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14.	Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.	Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
Measure Participants	33	36	35
Hypernatremia (sodium increased)	1 2.9%	1 2.8%	1 2.9%
Hyponatremia (sodium decreased)	0 0%	1 2.8%	0 0%
Hyperkalemia (potassium increased)	2 5.9%	1 2.8%	1 2.9%
Hypokalemia (potassium decreased)	0 0%	2 5.6%	0 0%
Creatinine increased	0 0%	3 8.3%	2 5.7%
Hypoglycemia (glucose decreased)	0 0%	1 2.8%	0 0%

Adverse Events

Time Frame	From first dose up to 30 days following the last dose of study drug (up to 45 days)
Adverse Event Reporting Description	Reported adverse events (AEs) are treatment-emergent adverse events (TEAEs) i.e., AEs that developed, worsened, or became serious during the treatment period (time from the first dose of study drug up to 30 days after last dose of study drug). Analysis was performed on safety population.
Arm/Group Title	Amcenestrant 400 mg		Amcenestrant 200 mg		Letrozole 2.5 mg
Arm/Group Description	Participants received 4 capsules of 100 mg of amcenestrant once daily (QD) from Day 1 to Day 14.		Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.		Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
All Cause Mortality
	Amcenestrant 400 mg		Amcenestrant 200 mg		Letrozole 2.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/36 (0%)		0/35 (0%)
Serious Adverse Events
	Amcenestrant 400 mg		Amcenestrant 200 mg		Letrozole 2.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		2/36 (5.6%)		0/35 (0%)
Infections and infestations
Pneumonia	0/33 (0%)	0	1/36 (2.8%)	1	0/35 (0%)	0
Wound Infection	0/33 (0%)	0	1/36 (2.8%)	1	0/35 (0%)	0
Other (Not Including Serious) Adverse Events
	Amcenestrant 400 mg		Amcenestrant 200 mg		Letrozole 2.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/33 (33.3%)		12/36 (33.3%)		14/35 (40%)
Gastrointestinal disorders
Constipation	1/33 (3%)	1	2/36 (5.6%)	2	1/35 (2.9%)	1
Diarrhoea	0/33 (0%)	0	3/36 (8.3%)	3	3/35 (8.6%)	3
General disorders
Asthenia	2/33 (6.1%)	2	2/36 (5.6%)	2	0/35 (0%)	0
Fatigue	2/33 (6.1%)	2	1/36 (2.8%)	1	1/35 (2.9%)	1
Feeling Cold	2/33 (6.1%)	2	0/36 (0%)	0	0/35 (0%)	0
Injury, poisoning and procedural complications
Procedural Pain	2/33 (6.1%)	2	1/36 (2.8%)	1	2/35 (5.7%)	2
Investigations
Alanine Aminotransferase Increased	1/33 (3%)	1	2/36 (5.6%)	2	0/35 (0%)	0
Metabolism and nutrition disorders
Decreased Appetite	2/33 (6.1%)	2	1/36 (2.8%)	1	0/35 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/33 (6.1%)	2	0/36 (0%)	0	3/35 (8.6%)	3
Nervous system disorders
Headache	3/33 (9.1%)	3	0/36 (0%)	0	2/35 (5.7%)	2
Psychiatric disorders
Anxiety	1/33 (3%)	1	2/36 (5.6%)	2	0/35 (0%)	0
Insomnia	4/33 (12.1%)	4	1/36 (2.8%)	1	0/35 (0%)	0
Reproductive system and breast disorders
Breast Pain	1/33 (3%)	1	0/36 (0%)	0	3/35 (8.6%)	3
Vascular disorders
Hot Flush	4/33 (12.1%)	4	1/36 (2.8%)	1	5/35 (14.3%)	5

Limitations/Caveats

The study recruitment discontinued early based on strategic sponsor decision that was not driven by any safety concerns. No inferential statistical analysis was performed due to early termination.

More Information

Certain Agreements

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

The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.