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Breast CancerPhase 2AMEERA-4NCT04191382

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

A Phase 2 study testing Amcenestrant (SAR439859) and Letrozole in people with Breast Cancer, run by Sanofi at 32 sites in 9 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Amcenestrant (SAR439859) and Letrozole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
105 participants
Where
32 sitesin 9 countries
Study dates
4 Feb 2020to 28 May 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

32 sites in 9 countries.

32 sites in 9 countries

United States6 sites

  • Investigational Site Number 8400018

    Fort Wayne, Indiana, 46804

  • Investigational Site Number 8400005

    Lincoln, Nebraska, 68506

  • Investigational Site Number 8400010

    Los Angeles, California, 90095

  • Investigational Site Number 8400012

    Tacoma, Washington, 98405

  • Investigational Site Number 8400014

    Tucson, Arizona, 85724

  • Investigational Site Number 8400016

    Winston-Salem, North Carolina, 27157

Other trials in United States

Russia5 sites

  • Investigational Site Number 6430006

    Moscow, 117186

  • Investigational Site Number 6430004

    Moscow, 119991

  • Investigational Site Number 6430003

    Saint Petersburg, 194156

  • Investigational Site Number 6430007

    Saint Petersburg, 195271

  • Investigational Site Number 6430002

    Saint Petersburg, 197758

Other trials in Russia

France4 sites

  • Investigational Site Number 2500001

    Nantes, 44093

  • Investigational Site Number 2500004

    Paris, 75010

  • Investigational Site Number 2500002

    Saint-Cloud, 92210

  • Investigational Site Number 2500003

    Toulouse, 31059

Other trials in France

Spain4 sites

  • Investigational Site Number 7240005

    Barcelona, 08003

  • Investigational Site Number 7240003

    Córdoba, 14004

  • Investigational Site Number 7240001

    Madrid, 28041

  • Investigational Site Number 7240002

    Valencia, 46010

Other trials in Spain

Ukraine4 sites

  • Investigational Site Number 8040004

    Kharkiv, 61166

  • Investigational Site Number 8040001

    Uzhhorod, 88000

  • Investigational Site Number 8040002

    Vinnytsia, 21029

  • Investigational Site Number 8040005

    Zaporizhzhya, 69040

Other trials in Ukraine

Italy3 sites

  • Investigational Site Number 3800004

    Meldola, 47014

  • Investigational Site Number 3800002

    Milan, 20132

  • Investigational Site Number 3800001

    Milan, 20141

Other trials in Italy

Japan3 sites

  • Investigational Site Number 3920002

    Osaka

  • Investigational Site Number 3920003

    Sapporo

  • Investigational Site Number 3920001

    Yokohama

Other trials in Japan

Belgium2 sites

  • Investigational Site Number 0560001

    Leuven, 3000

  • Investigational Site Number 0560002

    Namur, 5000

Other trials in Belgium

Puerto Rico1 site

  • Investigational Site Number 8400007

    Hato Rey, 00917

Other trials in Puerto Rico

About this study

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

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.
Read the 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.

Conditions
Breast Cancer
Being tested
Amcenestrant (SAR439859), Letrozole
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Amcenestrant (SAR439859)Drug

    Pharmaceutical form: Capsules, Route of administration: Oral

  • LetrozoleDrug

    Pharmaceutical form: Tablets, Route of administration: Oral

Study groups in NCT04191382
Study groupRoleWhat they receive
Amcenestrant 400 mgExperimentalParticipants received 4 capsules of 100 milligrams (mg) of amcenestrant once daily (QD) from Day 1 to Day 14.
Receives: Drug: Amcenestrant (SAR439859)
Amcenestrant 200 mgExperimentalParticipants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.
Receives: Drug: Amcenestrant (SAR439859)
Letrozole 2.5 mgActive comparatorParticipants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.
Receives: Drug: Letrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent Change From Baseline in Ki67 Level at 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.

    Measured: Baseline, Day 15

Secondary outcomes (4)

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

    Measured: Baseline, Day 15

  2. Change From Baseline in Estrogen Receptor (ER) Expression as Measured by H-Score at 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.

    Measured: Baseline, Day 15

  3. Number of Participants With Abnormalities: Hematological Parameters

    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.

    Measured: From first dose of study drug up to Day 14

  4. Number of Participants With Abnormalities: Clinical Chemistry

    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.

    Measured: From first dose of study drug up to Day 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2019
  2. Study start4 Feb 2020
  3. Primary completion30 Apr 2021
  4. Study completion28 May 2021

Why it stopped: early discontinuation based on strategic sponsor decision not driven by any safety concerns

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
105 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04191382
Sponsor's protocol ID
ACT16106
Other IDs
2019-002015-26, U1111-1228-9473, 2019
Acronym
AMEERA-4
Status last verified
Sep 2025
First submitted
5 Dec 2019
Last updated
18 Sep 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Publications

  • Campone M, Bidard FC, Neven P, Wang L, Ling B, Dong Y, Paux G, Herold C, De Giorgi U. AMEERA-4: a randomized, preoperative window-of-opportunity study of amcenestrant versus letrozole in early breast cancer. Breast Cancer Res. 2023 Nov 10;25(1):141. doi: 10.1186/s13058-023-01740-2.

    PubMed 37950338

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Amcenestrant (SAR439859) and Letrozole in people with Breast Cancer, run by Sanofi at 32 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in United States, Russia, France, Spain, Ukraine and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Ki67 Level at Day 15 (time frame: Baseline, Day 15). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04191382, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2025.

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