Amcenestrant (SAR439859) Plus Palbociclib as First Line Therapy for Patients With ER (+) HER2(-) Advanced Breast Cancer (AMEERA-5)

Sanofi

Status and phase: Terminated; Phase 3

Conditions: Breast Cancer

Treatments: Drug: SAR439859; Drug: Letrozole; Drug: Palbociclib; Drug: Amcenestrant-matching placebo; Drug: Letrozole-matching placebo; Drug: Goserelin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04478266

U1111-1233-0486 (Other Identifier)

EFC15935

2020-001824-33 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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

Enrollment: 1,068 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,068 participants in 2 patient groups

Letrozole + Palbociclib

Active Comparator group

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.

Treatment:

Drug: Goserelin

Drug: Amcenestrant-matching placebo

Drug: Letrozole

Drug: Palbociclib

Amcenestrant + Palbociclib

Experimental group

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.

Treatment:

Drug: Goserelin

Drug: Letrozole-matching placebo

Drug: Palbociclib

Drug: SAR439859