Evaluation of Orally Administered Amcenestrant (SAR439859) in Japanese Postmenopausal Patients With Advanced Breast Cancer (AMEERA-2) (AMEERA-2)

A Phase 1 Study for the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics Evaluation of SAR439859, Administered Orally as Monotherapy in Japanese Postmenopausal Women With Estrogen Receptor-Positive And Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer (AMEERA-2)

Primary Objective:

To assess the incidence rate of dose-limiting toxicity and to confirm the recommended dose as well as the maximum tolerated dose of SAR439859 administered as monotherapy to Japanese postmenopausal women with estrogen receptor positive and human epidermal growth factor receptor 2-negative advanced breast cancer.

Secondary Objective:

• To characterize the overall safety profile of SAR439859 administered as monotherapy.
• To characterize the pharmacokinetic profile of SAR439859 administered as monotherapy.
• To evaluate the antitumor activity of SAR439859 administered as monotherapy and the clinical benefit rate (complete response, partial response and stable disease ≥ 24 weeks).

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Amcenestrant (SAR439859)

Detailed Description

The duration of the study for an individual participant will include a period to assess eligibility (screening period) of up to 4 weeks (28 days), a treatment period of at least 1 cycle (28 days) of study treatment, and an End of Treatment (EOT) visit at least 30 days (or until the participant receives another anticancer therapy, whichever is earlier) following the last administration of study treatment. Study treatment may continue until precluded by unacceptable toxicity, disease progression, or upon participant's request.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 464-8681
      • Investigational Site Number : 3920003
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Investigational Site Number : 3920001
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Investigational Site Number : 3920002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria :

• Participants must be postmenopausal women.
• Breast adenocarcinoma patients with locally advanced not amenable to radiation or surgery, inoperable and/or metastatic disease.
• Either the primary or any metastatic site must be positive for estrogen receptor (ER) (>1% staining by immunohistochemistry).
• Either the primary tumor or any metastatic site must be human epidermal growth factor receptor 2 non-overexpressing.
• Patients with at least 6 months of prior endocrine therapy.

Exclusion criteria:

• Eastern Cooperative Oncology Group Performance Status (ECOG) ≥2.
• Significant concomitant illness that would adversely affect participation in the study.
• Patients with a life expectancy less than 3 months.
• Patient not suitable for participation, whatever the reason.
• Major surgery within 4 weeks prior to first study treatment administration.
• Treatment with strong and moderate cytochrome P450 3A inhibitors/inducers.
• Patients with known endometrial disorders, uterine bleeding or ovarian cysts.
• Treatment with anticancer less than 2 weeks before first study treatment.
• Prior treatment with selective estrogen receptor down (SERD)-regulator (except fulvestrant for which a washout of at least 6 weeks is required).
• Inadequate hematological function.
• Inadequate renal function with serum creatinine ≥1.5 x upper limit of normal (ULN).
• Liver function: aspartate aminotransferase >3 x ULN, or alanine aminotransferase >3 x ULN. Total bilirubin >1.5 x ULN.
• Non-resolution of any prior treatment related toxicity to <Grade 2, except for alopecia

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR439859; administered orally once daily or twice daily as monotherapy in fasted or fed state	Drug: Amcenestrant (SAR439859); Pharmaceutical form: Capsules Route of administration: Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigational medicinal product (IMP)-related dose limiting toxicities (DLTs)	Incidence rate of study treatment-related DLTs at Cycle 1	Day 1 to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Adverse Events (AEs)	Number of adverse events related to study therapy	Up to 30 days after administration of study treatment
Assessment of Pharmacokinetic parameter of SAR439859: tlag	Lag time, interval between administration time and the sampling time preceding the first concentration above the lower limit of quantification	Day 1 and Day 22 of Cycle 1 (28 days)
Assessment of Pharmacokinetic parameter of SAR439859: tmax	First time to reach Cmax	Day 1 and Day 22 of Cycle 1 (28 days)
Assessment of Pharmacokinetic parameter of SAR439859: Cmax	Maximum concentration observed	Day 1 and Day 22 of Cycle 1 (28 days)
Assessment of Pharmacokinetic parameter of SAR439859: AUC0-24h or AUC0-10h and/or AUC0-12h	Area under the plasma concentration versus time curve over the dosing interval (24 hours, 10 hours or 12 hours)	Day 1 and Day 22 of Cycle 1 (28 days)
Assessment of Pharmacokinetic parameter of SAR439859: Ctrough	Plasma concentration observed just before treatment administration during repeated dosing	Day 1, Day 8, Day 15 and Day 22 of Cycle 1 (28 days) and Day 1 of Cycle 2
Assessment of antitumor activity: Objective response rate (ORR)	Objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	64 weeks
Assessment of antitumor activity: Clinical benefit rate (CBR)	Clinical benefit rate is (CR [complete response] +PR [partial response] +SD [stable disease] ≥24 weeks) as per RECIST 1.1	64 weeks
Assessment of antitumor activity: Duration of response	Response duration defined as the time from initial response to the first documented tumor progression	64 weeks
Assessment of antitumor activity: Non-progression rate	Non-progression rate at 24 weeks (percentage of participants without progression at 24 weeks)	64 weeks

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

General Publications

• Tamura K, Mukohara T, Yonemori K, Kawabata Y, Nicolas X, Tanaka T, Iwata H. Phase 1 study of oral selective estrogen receptor degrader (SERD) amcenestrant (SAR439859), in Japanese women with ER-positive and HER2-negative advanced breast cancer (AMEERA-2). Breast Cancer. 2023 May;30(3):506-517. doi: 10.1007/s12282-023-01443-8. Epub 2023 Mar 29.

Helpful Links

• TED15954 Plain language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2019
• Primary Completion (Actual): October 27, 2020
• Study Completion (Actual): December 26, 2024

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: January 23, 2019
• First Posted (Actual): January 25, 2019

Study Record Updates

• Last Update Posted (Actual): July 7, 2025
• Last Update Submitted That Met QC Criteria: July 3, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: TED15954 (Sanofi Identifier); U1111-1217-2758 (Other Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No