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.
Study duration per participant is approximately 59 months, which includes a 33- month
treatment period.
Drug: Amcenestrant-matching placebo
Pharmaceutical form: Tablets Route of Administration: Oral
Drug: SAR439859
Pharmaceutical form: Tablets Route of Administration: Oral
Other Name: Amcenestrant
Drug: Palbociclib
Pharmaceutical form: Capsules/Tablets Route of Administration: Oral
Other Name: Ibrance
Drug: Letrozole
Pharmaceutical form: Capsules Route of Administration: Orally
Drug: Goserelin
Pharmaceutical form: Depot Injection Route of Administration: Subcutaneous
Drug: Letrozole-matching placebo
Pharmaceutical form: Capsules Route of Administration: Orally
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 is not intended to contain all considerations relevant to a
participant's potential participation in a clinical trial.
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
Saint 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
Cordoba, Córdoba, Argentina
Investigational Site Number :0320002
Rosario, Santa Fe, 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
Bruxelles, 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
Sao Paulo, São Paulo, Brazil
Investigational Site Number :0760003
Sao 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
Russe, 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, Chile
Investigational Site Number :1520004
Temuco, La Araucanía, Chile
Investigational Site Number :1520009
Talca, Maule, 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, Valparaíso, Chile
Investigational Site Number :1520003
Santiago de Chile, Chile
Investigational Site Number :1520007
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
Praha 2, 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 Cedex 9, 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 :3480011
Gyula, Hungary
Investigational Site Number :3480005
Győr, 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
Milano, Italy
Investigational Site Number :3800002
Milano, Italy
Investigational Site Number :3800006
Napoli, Italy
Investigational Site Number :3800005
Prato, Italy
Investigational Site Number :3920016
Nagoya-shi, Aichi, Japan
Investigational Site Number :3920007
Nagoya-shi, Aichi, Japan
Investigational Site Number :3920002
Kashiwa-shi, Chiba, Japan
Investigational Site Number :3920009
Matsuyama-shi, Ehime, Japan
Investigational Site Number :3920019
Kurume-shi, Fukuoka, Japan
Investigational Site Number :3920017
Takasaki-shi, Gunma, Japan
Investigational Site Number :3920010
Hiroshima-shi, Hiroshima, Japan
Investigational Site Number :3920001
Sapporo-shi, Hokkaido, Japan
Investigational Site Number :3920012
Kagoshima-shi, Kagoshima, Japan
Investigational Site Number :3920014
Yokohama-shi, Kanagawa, Japan
Investigational Site Number :3920006
Yokohama-shi, Kanagawa, Japan
Investigational Site Number :3920020
Sendai-shi, Miyagi, Japan
Investigational Site Number :3920022
Miyazaki-shi, Miyazaki, Japan
Investigational Site Number :3920008
Osaka-shi, Osaka, Japan
Investigational Site Number :3920018
Osaka-shi, Osaka, Japan
Investigational Site Number :3920013
Hidaka-shi, Saitama, Japan
Investigational Site Number :3920021
Shizuoka-shi, 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 :4100006
Goyang-si, Gyeonggi-do, Korea, Republic of
Investigational Site Number :4100005
Seongnam, Gyeonggi-do, Korea, Republic of
Investigational Site Number :4100007
Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :4100004
Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :4100003
Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :4100002
Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :4100001
Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :4100009
Seochogu, Korea, Republic of
Investigational Site Number :4100008
Seongnam-si, Gyeonggi-do, Korea, Republic of
Investigational Site Number :5280006
Arnhem, Netherlands
Investigational Site Number :5280005
Delft, Netherlands
Investigational Site Number :5280001
Maastricht, Netherlands
Investigational Site Number :6160002
Tomaszow Mazowiecki, Lódzkie, Poland
Investigational Site Number :6160007
Poznan, Wielkopolskie, Poland
Investigational Site Number :6200005
Almada, Portugal
Investigational Site Number :6200001
Lisboa, Portugal
Investigational Site Number :6200002
Porto, Portugal
Investigational Site Number :6430007
Arkhangelsk, Russian Federation
Investigational Site Number :6430004
Krasnogorskiy District, Russian Federation
Investigational Site Number :6430009
Moscow Region, Russian Federation
Investigational Site Number :6430008
Moscow, Russian Federation
Investigational Site Number :6430003
Moscow, Russian Federation
Investigational Site Number :6430005
Moscow, Russian Federation
Investigational Site Number :6430006
Moscow, Russian Federation
Investigational Site Number :6430001
Saint -Petersburg, Russian Federation
Investigational Site Number :6430010
Saint Petersburg, Russian Federation
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 :7240011
Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number :7240008
Barcelona / Sabadell, Castilla Y León, Spain
Investigational Site Number :7240003
Santiago de Compostela, Galicia [Galicia], Spain
Investigational Site Number :7240006
Madrid / Madrid, Madrid, Comunidad De, Spain
Investigational Site Number :7240002
Madrid / Madrid, Madrid, Comunidad De, Spain
Investigational Site Number :7240004
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, Taiwan
Investigational Site Number :1580002
Tainan, Taiwan
Investigational Site Number :1580001
Taipei, Taiwan
Investigational Site Number :1580003
Taipei, Taiwan
Investigational Site Number :7920006
Adana, Turkey
Investigational Site Number :7920008
Ankara, Turkey
Investigational Site Number :7920009
Ankara, Turkey
Investigational Site Number :7920007
Antalya, Turkey
Investigational Site Number :7920005
Bornova, Turkey
Investigational Site Number :7920013
Diyarbakır, Turkey
Investigational Site Number :7920003
Edirne, Turkey
Investigational Site Number :7920001
Istanbul, Turkey
Investigational Site Number :7920011
Istanbul, Turkey
Investigational Site Number :7920004
Istanbul, Turkey
Investigational Site Number :7920012
İzmir, Turkey
Investigational Site Number :7920010
Kocaeli, Turkey
Investigational Site Number :7920002
Malatya, Turkey
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
Clinical Sciences & Operations, Study Director
Sanofi