Amcenestrant (SAR439859) Plus Palbociclib as First Line Therapy for Patients With ER (+) HER2(-) Advanced Breast Cancer

NCT ID: NCT04478266

Last Updated: 2025-09-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 1068 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-14
• Study Completion Date: 2023-05-26

Brief Summary

Primary Objective:

To determine whether Amcenestrant (SAR439859) in combination with palbociclib improves progression free survival (PFS) when compared with letrozole in combination with palbociclib in participants with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who have not received any prior systemic anticancer therapies for advanced disease.

Secondary Objective:

• To compare the overall survival in both treatment arms.
• To evaluate the objective response rate in both treatment arms.
• To evaluate the duration of response in both treatment arms.
• To evaluate the clinical benefit rate in both treatment arms.
• To evaluate progression-free survival on next line of therapy.
• To evaluate the pharmacokinetics of amcenestrant, and palbociclib.
• To evaluate health-related quality of life in both treatment arms.
• To evaluate the time to first chemotherapy in both treatment arms.
• To evaluate safety in both treatment arms.

Detailed Description

Study duration per participant was approximately 59 months, which includes a 33- month treatment period.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Letrozole + Palbociclib

Participants received letrozole 2.5 milligrams (mg) capsule along with amcenestrant-matching placebo once daily, continuously and palbociclib 125 mg orally (PO), once daily (QD) from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death or study cut-off date, whichever comes first (maximum exposure: 112 weeks). Goserelin once every 4 weeks in pre/peri menopausal women and men.

Group Type: ACTIVE_COMPARATOR

Amcenestrant-matching placebo

Intervention Type: DRUG

Pharmaceutical form: Tablets Route of Administration: Oral

Palbociclib

Intervention Type: DRUG

Pharmaceutical form: Capsules/Tablets Route of Administration: Oral

Letrozole

Intervention Type: DRUG

Pharmaceutical form: Capsules Route of Administration: Orally

Goserelin

Intervention Type: DRUG

Pharmaceutical form: Depot Injection Route of Administration: Subcutaneous

Amcenestrant + Palbociclib

Participants received amcenestrant 200 mg tablet along with letrozole-matching placebo once daily, continuously and palbociclib 125 mg PO, QD from Day 1 to Day 21 of each 28-day treatment cycle until disease progression, death, or study cut-off date, whichever comes first (maximum exposure: 109 weeks). Goserelin once every 4 weeks in pre/peri menopausal women and men.

Group Type: EXPERIMENTAL

SAR439859

Intervention Type: DRUG

Pharmaceutical form: Tablets Route of Administration: Oral

Palbociclib

Intervention Type: DRUG

Pharmaceutical form: Capsules/Tablets Route of Administration: Oral

Goserelin

Intervention Type: DRUG

Pharmaceutical form: Depot Injection Route of Administration: Subcutaneous

Letrozole-matching placebo

Intervention Type: DRUG

Pharmaceutical form: Capsules Route of Administration: Orally

Interventions

Amcenestrant-matching placebo

Pharmaceutical form: Tablets Route of Administration: Oral

Intervention Type: DRUG

SAR439859

Pharmaceutical form: Tablets Route of Administration: Oral

Intervention Type: DRUG

Palbociclib

Pharmaceutical form: Capsules/Tablets Route of Administration: Oral

Intervention Type: DRUG

Letrozole

Pharmaceutical form: Capsules Route of Administration: Orally

Intervention Type: DRUG

Goserelin

Pharmaceutical form: Depot Injection Route of Administration: Subcutaneous

Intervention Type: DRUG

Letrozole-matching placebo

Pharmaceutical form: Capsules Route of Administration: Orally

Intervention Type: DRUG

Other Intervention Names

Amcenestrant; Ibrance

Eligibility Criteria

Inclusion Criteria

• Adult participants with loco-regional recurrent or metastatic disease not amenable to curative treatment.
• Confirmed diagnosis of ER+/HER2- breast cancer.
• No prior systemic treatment for loco-regional recurrent or metastatic disease.
• Measurable disease evaluable per Response Evaluation Criterion in Solid Tumors (RECIST) v.1.1 or non-measurable bone-only disease.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Participants should be willing to provide tumor tissue.
• Capable of giving informed consent.

Exclusion Criteria

• Known active brain metastases.
• Prior neo (adjuvant) treatment with any selective estrogen receptor degrader (SERD).
• Inadequate organ and marrow function.
• Disease recurrence while on, or within 12 months of completion of (neo)adjuvant endocrine therapy.
• Pregnant, breastfeeding, or woman of childbearing potential unwilling to use recommended contraception methods.
• Male participants who disagree to follow contraception.
• Participants with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term.
• Participants with significant concomitant illness.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number :8400075

Daphne, Alabama, United States

Investigational Site Number :8400083

Glendale, Arizona, United States

Investigational Site Number :8400066

Tucson, Arizona, United States

Investigational Site Number :8400038

Fullerton, California, United States

Investigational Site Number :8400056

Los Alamitos, California, United States

Investigational Site Number :8400029

Santa Monica, California, United States

Investigational Site Number :8400025

Denver, Colorado, United States

Investigational Site Number :8400059

Lakeland, Florida, United States

Investigational Site Number :8400053

Orlando, Florida, United States

Investigational Site Number :8400081

Palm Bay, Florida, United States

Investigational Site Number :8400055

Athens, Georgia, United States

Investigational Site Number :8400016

Atlanta, Georgia, United States

Investigational Site Number :8400034

Savannah, Georgia, United States

Investigational Site Number :8400035

Thomasville, Georgia, United States

Investigational Site Number :8400039

Chicago, Illinois, United States

Investigational Site Number :8400008

Fort Wayne, Indiana, United States

Investigational Site Number :8400006

Iowa City, Iowa, United States

Investigational Site Number :8400013

Westwood, Kansas, United States

Investigational Site Number :8400028

Scarborough, Maine, United States

Investigational Site Number :8400017

Boston, Massachusetts, United States

Investigational Site Number :8400076

Danvers, Massachusetts, United States

Investigational Site Number :8400077

Newton, Massachusetts, United States

Investigational Site Number :8400002

Ann Arbor, Michigan, United States

Investigational Site Number :8400005

Kansas City, Missouri, United States

Investigational Site Number :8400004

St Louis, Missouri, United States

Investigational Site Number :8400058

Las Vegas, Nevada, United States

Investigational Site Number :8400015

New Brunswick, New Jersey, United States

Investigational Site Number :8400024

Paramus, New Jersey, United States

Investigational Site Number :8400010

New York, New York, United States

Investigational Site Number :8400023

Stony Brook, New York, United States

Investigational Site Number :8400009

Winston-Salem, North Carolina, United States

Investigational Site Number :8400067

Tigard, Oregon, United States

Investigational Site Number :8400001

Pittsburgh, Pennsylvania, United States

Investigational Site Number :8400073

Austin, Texas, United States

Investigational Site Number :8400072

Dallas, Texas, United States

Investigational Site Number :8400070

Dallas, Texas, United States

Investigational Site Number :8400080

Denton, Texas, United States

Investigational Site Number :8400061

Houston, Texas, United States

Investigational Site Number :8400068

Houston, Texas, United States

Investigational Site Number :8400084

Plano, Texas, United States

Investigational Site Number :8400086

The Woodlands, Texas, United States

Investigational Site Number :8400078

Waco, Texas, United States

Investigational Site Number :8400082

Webster, Texas, United States

Investigational Site Number :8400085

Blacksburg, Virginia, United States

Investigational Site Number :8400069

Winchester, Virginia, United States

Investigational Site Number :0320001

CABA, Buenos Aires, Argentina

Investigational Site Number :0320005

CABA, Buenos Aires, Argentina

Investigational Site Number :0320008

Capital Federal, Buenos Aires, Argentina

Investigational Site Number :0320006

Pergamino, Buenos Aires, Argentina

Investigational Site Number :0320010

Córdoba, Córdoba Province, Argentina

Investigational Site Number :0320002

Rosario, Santa Fe Province, Argentina

Investigational Site Number :0320004

Buenos Aires, , Argentina

Investigational Site Number :0320003

La Rioja, , Argentina

Investigational Site Number :0320009

Mar del Plata, , Argentina

Investigational Site Number :0320007

Salta, , Argentina

Investigational Site Number :0360004

Macquarie Park, New South Wales, Australia

Investigational Site Number :0360005

Randwick, New South Wales, Australia

Investigational Site Number :0360003

Wahroonga, New South Wales, Australia

Investigational Site Number :0360002

Richmond, Victoria, Australia

Investigational Site Number :0360001

Nedlands, Western Australia, Australia

Investigational Site Number :0400001

Graz, , Austria

Investigational Site Number :0560003

Brussels, , Belgium

Investigational Site Number :0560004

Charleroi, , Belgium

Investigational Site Number :0560001

Leuven, , Belgium

Investigational Site Number :0560002

Namur, , Belgium

Investigational Site Number :0760005

Porto Alegre, Rio Grande do Sul, Brazil

Investigational Site Number :0760006

Porto Alegre, Rio Grande do Sul, Brazil

Investigational Site Number :0760007

São Paulo, São Paulo, Brazil

Investigational Site Number :0760003

São Paulo, São Paulo, Brazil

Investigational Site Number :0760004

Rio de Janeiro, , Brazil

Investigational Site Number :0760008

São Paulo, , Brazil

Investigational Site Number :1000004

Burgas, , Bulgaria

Investigational Site Number :1000005

Dobrich, , Bulgaria

Investigational Site Number :1000008

Rousse, , Bulgaria

Investigational Site Number :1000001

Sofia, , Bulgaria

Investigational Site Number :1240004

Kingston, Ontario, Canada

Investigational Site Number :1240002

Toronto, Ontario, Canada

Investigational Site Number :1240007

Greenfield Park, Quebec, Canada

Investigational Site Number :1240014

Montreal, Quebec, Canada

Investigational Site Number :1240005

Montreal, Quebec, Canada

Investigational Site Number :1520005

La Serena, Coquimbo Region, Chile

Investigational Site Number :1520004

Temuco, La Araucanía, Chile

Investigational Site Number :1520009

Talca, Maule Region, Chile

Investigational Site Number :1520011

Santaigo, Reg Metropolitana de Santiago, Chile

Investigational Site Number :1520006

Santiago, Reg Metropolitana de Santiago, Chile

Investigational Site Number :1520002

Santiago, Reg Metropolitana de Santiago, Chile

Investigational Site Number :1520001

Viña del Mar, Región de Valparaíso, Chile

Investigational Site Number :1520007

Santiago, , Chile

Investigational Site Number :1520003

Santiago, , Chile

Investigational Site Number :1560038

Baoding, , China

Investigational Site Number :1560008

Beijing, , China

Investigational Site Number :1560035

Beijing, , China

Investigational Site Number :1560003

Changchun, , China

Investigational Site Number :1560036

Changchun, , China

Investigational Site Number :1560013

Chengdu, , China

Investigational Site Number :1560019

Chongqing, , China

Investigational Site Number :1560031

Dalian, , China

Investigational Site Number :1560021

Dalian, , China

Investigational Site Number :1560054

Deyang, , China

Investigational Site Number :1560043

Fuzhou, , China

Investigational Site Number :1560025

Guangzhou, , China

Investigational Site Number :1560006

Hangzhou, , China

Investigational Site Number :1560007

Hangzhou, , China

Investigational Site Number :1560002

Hangzhou, , China

Investigational Site Number :1560005

Hangzhou, , China

Investigational Site Number :1560011

Harbin, , China

Investigational Site Number :1560041

Hefei, , China

Investigational Site Number :1560018

Jinan, , China

Investigational Site Number :1560046

Jinan, , China

Investigational Site Number :1560051

Jining, , China

Investigational Site Number :1560017

Linyi, , China

Investigational Site Number :1560055

Luoyang, , China

Investigational Site Number :1560048

Neijiang, , China

Investigational Site Number :1560001

Shanghai, , China

Investigational Site Number :1560037

Shaoguan, , China

Investigational Site Number :1560028

Tianjin, , China

Investigational Site Number :1560033

Wuhan, , China

Investigational Site Number :1560024

Wuhan, , China

Investigational Site Number :1560045

Xi'an, , China

Investigational Site Number :1560044

Xi'an, , China

Investigational Site Number :1560027

Xuzhou, , China

Investigational Site Number :1560049

Yantai, , China

Investigational Site Number :1560022

Zhengzhou, , China

Investigational Site Number :2030001

Brno, , Czechia

Investigational Site Number :2030002

Prague, , Czechia

Investigational Site Number :2460001

Helsinki, , Finland

Investigational Site Number :2460002

Tampere, , Finland

Investigational Site Number :2460003

Turku, , Finland

Investigational Site Number :2500009

Nice, , France

Investigational Site Number :2500003

Paris, , France

Investigational Site Number :2500001

Paris, , France

Investigational Site Number :2500006

Poitiers, , France

Investigational Site Number :2500007

Saint-Cloud, , France

Investigational Site Number :2500002

Saint-Herblain, , France

Investigational Site Number :2500010

Strasbourg, , France

Investigational Site Number :2500005

Toulouse, , France

Investigational Site Number :2500004

Villejuif, , France

Investigational Site Number :2680005

Batumi, , Georgia

Investigational Site Number :2680006

Kutaisi, , Georgia

Investigational Site Number :2680001

Tbilisi, , Georgia

Investigational Site Number :2680002

Tbilisi, , Georgia

Investigational Site Number :2680004

Tbilisi, , Georgia

Investigational Site Number :2680007

Tbilisi, , Georgia

Investigational Site Number :2680003

Tbilisi, , Georgia

Investigational Site Number :2760006

Bottrop, , Germany

Investigational Site Number :2760003

Münster, , Germany

Investigational Site Number :2760007

Oldenburg in Holstein, , Germany

Investigational Site Number :2760001

Ulm, , Germany

Investigational Site Number :3480008

Budapest, , Hungary

Investigational Site Number :3480005

Győr, , Hungary

Investigational Site Number :3480011

Gyula, , Hungary

Investigational Site Number :3480003

Kaposvár, , Hungary

Investigational Site Number :3480009

Kecskemét, , Hungary

Investigational Site Number :3480010

Miskolc, , Hungary

Investigational Site Number :3480001

Nyíregyháza, , Hungary

Investigational Site Number :3800008

Meldola (FC), Emilia-Romagna, Italy

Investigational Site Number :3800003

Rozzano, Milano, Italy

Investigational Site Number :3800007

Monza, Monza E Brianza, Italy

Investigational Site Number :3800010

Bologna, , Italy

Investigational Site Number :3800004

Milan, , Italy

Investigational Site Number :3800002

Milan, , Italy

Investigational Site Number :3800006

Napoli, , Italy

Investigational Site Number :3800005

Prato, , Italy

Investigational Site Number :3920016

Nagoya, Aichi-ken, Japan

Investigational Site Number :3920007

Nagoya, Aichi-ken, Japan

Investigational Site Number :3920002

Kashiwa-shi, Chiba, Japan

Investigational Site Number :3920009

Matsuyama, Ehime, Japan

Investigational Site Number :3920019

Kurume-shi, Fukuoka, Japan

Investigational Site Number :3920017

Takasaki-shi, Gunma, Japan

Investigational Site Number :3920010

Hiroshima, Hiroshima, Japan

Investigational Site Number :3920001

Sapporo, Hokkaido, Japan

Investigational Site Number :3920012

Kagoshima, Kagoshima-ken, Japan

Investigational Site Number :3920014

Yokohama, Kanagawa, Japan

Investigational Site Number :3920006

Yokohama, Kanagawa, Japan

Investigational Site Number :3920020

Sendai, Miyagi, Japan

Investigational Site Number :3920022

Miyazaki, Miyazaki, Japan

Investigational Site Number :3920008

Osaka, Osaka, Japan

Investigational Site Number :3920018

Osaka, Osaka, Japan

Investigational Site Number :3920013

Hidaka-shi, Saitama, Japan

Investigational Site Number :3920021

Shizuoka, Shizuoka, Japan

Investigational Site Number :3920003

Koto-ku, Tokyo, Japan

Investigational Site Number :3920015

Meguro-ku, Tokyo, Japan

Investigational Site Number :3920005

Shinagawa-ku, Tokyo, Japan

Investigational Site Number :5280006

Arnhem, , Netherlands

Investigational Site Number :5280005

Delft, , Netherlands

Investigational Site Number :5280001

Maastricht, , Netherlands

Investigational Site Number :6160007

Poznan, Greater Poland Voivodeship, Poland

Investigational Site Number :6160002

Tomaszów Mazowiecki, Lódzkie, Poland

Investigational Site Number :6200005

Almada, , Portugal

Investigational Site Number :6200001

Lisbon, , Portugal

Investigational Site Number :6200002

Porto, , Portugal

Investigational Site Number :6430007

Arkhangelsk, , Russia

Investigational Site Number :6430004

Krasnogorskiy District, , Russia

Investigational Site Number :6430008

Moscow, , Russia

Investigational Site Number :6430003

Moscow, , Russia

Investigational Site Number :6430005

Moscow, , Russia

Investigational Site Number :6430006

Moscow, , Russia

Investigational Site Number :6430009

Moscow Region, , Russia

Investigational Site Number :6430001

Saint Petersburg, , Russia

Investigational Site Number :6430010

Saint Petersburg, , Russia

Investigational Site Number :7020002

Singapore, , Singapore

Investigational Site Number :7020004

Singapore, , Singapore

Investigational Site Number :7020001

Singapore, , Singapore

Investigational Site Number :7100004

Cape Town, , South Africa

Investigational Site Number :7100006

Johannesburg, , South Africa

Investigational Site Number :4100006

Goyang-si, Gyeonggi-do, South Korea

Investigational Site Number :4100005

Seongnam-si, Gyeonggi-do, South Korea

Investigational Site Number :4100007

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number :4100004

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number :4100003

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number :4100002

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number :4100001

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number :4100009

Seochogu, , South Korea

Investigational Site Number :4100008

Seongnam-si, Gyeonggi-do, , South Korea

Investigational Site Number :7240011

Barcelona, Barcelona [Barcelona], Spain

Investigational Site Number :7240008

Barcelona / Sabadell, Castille and León, Spain

Investigational Site Number :7240003

Santiago de Compostela, Galicia [Galicia], Spain

Investigational Site Number :7240004

Madrid, Madrid, Comunidad de, Spain

Investigational Site Number :7240006

Madrid / Madrid, Madrid, Comunidad de, Spain

Investigational Site Number :7240002

Madrid / Madrid, Madrid, Comunidad de, Spain

Investigational Site Number :7240005

Valencia, Valenciana, Comunidad, Spain

Investigational Site Number :7240001

Madrid, , Spain

Investigational Site Number :7240007

Málaga, , Spain

Investigational Site Number :7240009

Valencia, , Spain

Investigational Site Number :1580007

Kaohsiung City, , Taiwan

Investigational Site Number :1580002

Tainan City, , Taiwan

Investigational Site Number :1580001

Taipei, , Taiwan

Investigational Site Number :1580003

Taipei, , Taiwan

Investigational Site Number :7920006

Adana, , Turkey (Türkiye)

Investigational Site Number :7920008

Ankara, , Turkey (Türkiye)

Investigational Site Number :7920009

Ankara, , Turkey (Türkiye)

Investigational Site Number :7920007

Antalya, , Turkey (Türkiye)

Investigational Site Number :7920005

Bornova, , Turkey (Türkiye)

Investigational Site Number :7920013

Diyarbakır, , Turkey (Türkiye)

Investigational Site Number :7920003

Edirne, , Turkey (Türkiye)

Investigational Site Number :7920001

Istanbul, , Turkey (Türkiye)

Investigational Site Number :7920011

Istanbul, , Turkey (Türkiye)

Investigational Site Number :7920004

Istanbul, , Turkey (Türkiye)

Investigational Site Number :7920012

Izmir, , Turkey (Türkiye)

Investigational Site Number :7920010

Kocaeli, , Turkey (Türkiye)

Investigational Site Number :7920002

Malatya, , Turkey (Türkiye)

Investigational Site Number :8040004

Kharkiv, , Ukraine

Investigational Site Number :8040010

Kharkiv, , Ukraine

Investigational Site Number :8040001

Kryvyi Rih, , Ukraine

Investigational Site Number :8040002

Odesa, , Ukraine

Investigational Site Number :8040007

Vinnytsia, , Ukraine

Investigational Site Number :8260001

Glasgow, Central Bedfordshire, United Kingdom

Investigational Site Number :8260002

Edinburgh, Edinburgh, City of, United Kingdom

Investigational Site Number :8260005

Blackburn, Lancashire, United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Bulgaria; Canada; Chile; China; Czechia; Finland; France; Georgia; Germany; Hungary; Italy; Japan; Netherlands; Poland; Portugal; Russia; Singapore; South Africa; South Korea; Spain; Taiwan; Turkey (Türkiye); Ukraine; United Kingdom

References

Cortes J, Hurvitz SA, O'Shaughnessy J, Delaloge S, Iwata H, Rugo HS, Neven P, Kanagavel D, Cohen P, Paux G, Cartot-Cotton S, Stefanova-Urena M, Deyme L, Aouni J, Sebastien B, Bardia A. Randomized Phase III Study of Amcenestrant Plus Palbociclib Versus Letrozole Plus Palbociclib in Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Primary Results From AMEERA-5. J Clin Oncol. 2024 Aug 1;42(22):2680-2690. doi: 10.1200/JCO.23.02036. Epub 2024 Jun 18.

Reference Type: DERIVED

PMID: 38889373 (View on PubMed)

Bardia A, Cortes J, Hurvitz SA, Delaloge S, Iwata H, Shao ZM, Kanagavel D, Cohen P, Liu Q, Cartot-Cotton S, Pelekanou V, O'Shaughnessy J. AMEERA-5: a randomized, double-blind phase 3 study of amcenestrant plus palbociclib versus letrozole plus palbociclib for previously untreated ER+/HER2- advanced breast cancer. Ther Adv Med Oncol. 2022 Mar 15;14:17588359221083956. doi: 10.1177/17588359221083956. eCollection 2022.

Reference Type: DERIVED

PMID: 35309087 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.trialsummaries.com/Study/StudyDetails?id=25234&tenant=MT_SNY_9011

EFC15935 Plain Language Results Summary

Other Identifiers

2020-001824-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1233-0486

Identifier Type: OTHER

Identifier Source: secondary_id

EFC15935

Identifier Type: -

Identifier Source: org_study_id