Clinical trial · Interventional
Amcenestrant (SAR439859) Plus Palbociclib as First Line Therapy for Patients With ER (+) HER2(-) Advanced Breast Cancer
A Randomized, Multicenter, Double-blind Phase 3 Study of Amcenestrant (SAR439859) Plus Palbociclib Versus Letrozole Plus Palbociclib for the Treatment of Patients With ER (+), HER2 (-) Breast Cancer Who Have Not Received Prior Systemic Anti-cancer Treatment for Advanced Disease
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): The study was terminated based on the review by an independent data monitoring committee of the prespecified interim analysis of the Phase 3 AMEERA-5 efficacy data. No new safety signals were observed.
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Breast Cancer | Malignant Breast Neoplasm | CURATED_EXACT | 0.92 |
Interventions
Interventions (6)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Amcenestrant-matching placebo | Drug | — | UNRESOLVED |
| Goserelin | Drug | Goserelin | ALIAS |
| Letrozole | Drug | Letrozole | ALIAS |
| Letrozole-matching placebo | Drug | — | UNRESOLVED |
| Palbociclib | Drug | Palbociclib | ALIAS |
| SAR439859 | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- ACTIVE_COMPARATOR
- label
- Letrozole + Palbociclib
- description
- 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.
- interventionNames
- Drug: Amcenestrant-matching placebo
- Drug: Palbociclib
- Drug: Letrozole
- Drug: Goserelin
- type
- EXPERIMENTAL
- label
- Amcenestrant + Palbociclib
- description
- 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.
- interventionNames
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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.
References
Publications (2)
- DERIVEDCortes 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. PMID 38889373
- DERIVEDBardia 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. PMID 35309087