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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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)

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Amcenestrant (SAR439859)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |