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

NCT04191382 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: ACT161062019-002015-26U1111-1228-9473
• Study Type: interventional
• Target: 105
• Locations: 9 countries
• Sites: 32

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (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.

  Baseline, Day 15

Secondary Outcomes (4)

• Percentage of Participants With Percent Change From Baseline in Ki67 Greater Than or Equal to (>=) 50 Percent at Day 15

  Baseline, Day 15

• Change From Baseline in Estrogen Receptor (ER) Expression as Measured by H-Score at Day 15

  Baseline, Day 15

• Number of Participants With Abnormalities: Hematological Parameters

  From first dose of study drug up to Day 14

• Number of Participants With Abnormalities: Clinical Chemistry

  From first dose of study drug up to Day 14

Study Arms (3)

Amcenestrant 400 mg

EXPERIMENTAL

Participants received 4 capsules of 100 milligrams (mg) of amcenestrant once daily (QD) from Day 1 to Day 14.

Drug: Amcenestrant (SAR439859)

Amcenestrant 200 mg

EXPERIMENTAL

Participants received 2 capsules of 100 mg of amcenestrant QD from Day 1 to Day 14.

Drug: Amcenestrant (SAR439859)

Letrozole 2.5 mg

ACTIVE COMPARATOR

Participants received 2.5 mg of letrozole tablet QD from Day 1 to Day 14.

Drug: Letrozole

Interventions

Amcenestrant (SAR439859) DRUG

Pharmaceutical form: Capsules, Route of administration: Oral

Amcenestrant 200 mg; Amcenestrant 400 mg

Letrozole DRUG

Pharmaceutical form: Tablets, Route of administration: Oral

Letrozole 2.5 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (32)

Investigational Site Number 8400014

Tucson, Arizona, 85724, United States

Location

Investigational Site Number 8400010

Los Angeles, California, 90095, United States

Location

Investigational Site Number 8400018

Fort Wayne, Indiana, 46804, United States

Location

Investigational Site Number 8400005

Lincoln, Nebraska, 68506, United States

Location

Investigational Site Number 8400016

Winston-Salem, North Carolina, 27157, United States

Location

Investigational Site Number 8400012

Tacoma, Washington, 98405, United States

Location

Investigational Site Number 0560001

Leuven, 3000, Belgium

Location

Investigational Site Number 0560002

Namur, 5000, Belgium

Location

Investigational Site Number 2500001

Nantes, 44093, France

Location

Investigational Site Number 2500004

Paris, 75010, France

Location

Investigational Site Number 2500002

Saint-Cloud, 92210, France

Location

Investigational Site Number 2500003

Toulouse, 31059, France

Location

Investigational Site Number 3800004

Meldola, 47014, Italy

Location

Investigational Site Number 3800002

Milan, 20132, Italy

Location

Investigational Site Number 3800001

Milan, 20141, Italy

Location

Investigational Site Number 3920002

Osaka, Japan

Location

Investigational Site Number 3920003

Sapporo, Japan

Location

Investigational Site Number 3920001

Yokohama, Japan

Location

Investigational Site Number 8400007

Hato Rey, 00917, Puerto Rico

Location

Investigational Site Number 6430006

Moscow, 117186, Russia

Location

Investigational Site Number 6430004

Moscow, 119991, Russia

Location

Investigational Site Number 6430003

Saint Petersburg, 194156, Russia

Location

Investigational Site Number 6430007

Saint Petersburg, 195271, Russia

Location

Investigational Site Number 6430002

Saint Petersburg, 197758, Russia

Location

Investigational Site Number 7240005

Barcelona, 08003, Spain

Location

Investigational Site Number 7240003

Córdoba, 14004, Spain

Location

Investigational Site Number 7240001

Madrid, 28041, Spain

Location

Investigational Site Number 7240002

Valencia, 46010, Spain

Location

Investigational Site Number 8040004

Kharkiv, 61166, Ukraine

Location

Investigational Site Number 8040001

Uzhhorod, 88000, Ukraine

Location

Investigational Site Number 8040002

Vinnytsia, 21029, Ukraine

Location

Investigational Site Number 8040005

Zaporizhzhya, 69040, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 37950338 DERIVED

Related Links

• ACT16106 Plain Language Results Summary

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and 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.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: December 9, 2019
• Study Start: February 4, 2020
• Primary Completion: April 30, 2021
• Study Completion: May 28, 2021
• Last Updated: September 18, 2025
• Results First Posted: June 29, 2022

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

PR (1); IT (3); RU (5); JP (3); ES (4); US (6); UA (4); BE (2); FR (4)