SAR439859 with or without Palbociclib in ER+ breast cancer patients
Research type
Research Study
Full title
A Phase 1/2 study for the safety, efficacy, pharmacokinetic and pharmacodynamics evaluation of SAR439859, administered orally as monotherapy, then in combination with palbociclib in postmenopausal women with estrogen receptor-positive advanced breast cancer
IRAS ID
252017
Contact name
Robert Jones
Contact email
Sponsor organisation
Sanofi-aventis recherche & développement
Eudract number
2017-000690-36
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
U1111-1189-4896, WHO universal trial number:; 133204, IND Number:
Duration of Study in the UK
1 years, 10 months, 17 days
Research summary
The growth of some breast cancers is stimulated by hormones binding to receptors attached to them. In oestrogen-receptor (ER) positive breast cancer the growth of cancerous cells is stimulated by oestrogen (a hormone). The presence or absence of another receptor called HER2 also influences tumour growth and potential treatment options.
SAR439859 is a type of drug called a Selective Oestrogen Receptor Down-Regulator (SERD), which blocks the binding of oestrogen to the ER.
In this study we aim to enrol participants who are postmenopausal women with ER-positive HER2-negative advanced or metastatic breast cancer. The study consists of 4 parts (A, B, C & D); only parts B and D will be running in the UK. Participants enrolled in Part B will receive SAR439859 alone and participants enrolled in Part D will receive SAR439859 and palbociclib. Both medicines are given by mouth.
The main purpose of this study is to assess the efficacy and side effects of SAR439859 when given alone and in combination with palbociclib. The anti-tumour activity and blood levels of SAR439859 and palbociclib will be analysed as well as changes to genes associated with the disease. If patients consent, a blood sample will be taken to test genes that could affect the blood levels of SAR429859 and how SAR429859 works and in Part B up to 2 biopsies will be taken to assess degradation of ER.
The study will include approximately 156 participants, about 12 of whom will be from the UK.
The participants can continue to take the study medication unless their disease worsens, they have side effects that are considered unacceptable, or they or their doctor decide not to continue treatment.
A pharmaceutical company (Sanofi) is sponsoring this study.
The study is planned to take part in 3 NHS centres in England, Scotland & Wales.
LAY SUMMARY OF STUDY RESULTS:
AMEERA-1 was a Phase 1/2 study evaluating amcenestrant (SAR439859), an oral selective estrogen receptor degrader (SERD), in postmenopausal women with estrogen receptor positive advanced breast cancer. The study showed that amcenestrant had a favorable safety profile with no dose limiting toxicities. The recommended Phase 2 dose was established at 400 mg once daily. The drug demonstrated high estrogen receptor occupancy (96.7%) across multiple tumor sites. In heavily pretreated patients, the objective response rate was 8.5% and clinical benefit rate was 33.9%. Amcenestrant showed activity regardless of ESR1 mutation status, including in tumors with mutations known to be resistant to other treatments.REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
18/WM/0313
Date of REC Opinion
17 Dec 2018
REC opinion
Further Information Favourable Opinion