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Amcenestrant Combinations for Breast Cancer (AMEERA-1 Trial)

Phase 1 & 2

Waitlist Available

Research Sponsored by Sanofi

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Either primary tumor or any metastatic site to be positive for Estrogen Receptors (ER+) and negative for HER2 (HER2-) receptor

Locally advanced or metastatic disease

Must not have

Treatment with OATP1B1/B3 sensitive substrates and which cannot be replaced

Prior treatment with another selective ER down-regulator (SERD)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline and one assessment in cycle 1 on day 11 to 15 (each cycle is 28 days)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug, amcenestrant, to see if it is safe and effective for treating breast cancer. The trial will test different doses of amcenestrant to find the maximum tolerated dose (MTD), and will also test amcenestrant in combination with other drugs to see if it is safe and effective.

Who is the study for?

This trial is for postmenopausal women with advanced breast cancer that's ER+ and HER2-. Participants can have had limited prior endocrine or chemotherapy treatments, depending on the study arm. They must not have severe concurrent illnesses, certain drug interactions, or a history of specific conditions like uncontrolled diabetes or brain metastases.

What is being tested?

The trial tests Amcenestrant alone and in combination with other anti-cancer drugs (Palbociclib, Alpelisib, Everolimus, Abemaciclib) to find safe dosages and assess their effectiveness against breast cancer. It includes dose escalation to determine maximum tolerated doses and expansion phases to evaluate antitumor activity.

What are the potential side effects?

Potential side effects may include reactions at the infusion site, fatigue, digestive issues like nausea or diarrhea, blood-related problems such as anemia or clotting disorders. There could also be increased risk of infections due to immune system suppression.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is positive for estrogen receptors and negative for HER2.

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My cancer has spread beyond its original location.

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I have advanced disease and my first treatment was with Aromatase Inhibitors and CDK4/6 inhibitors.

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I have had no more than 2 prior endocrine treatments for my advanced disease.

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I am a woman who has gone through menopause.

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My breast cancer is diagnosed as adenocarcinoma.

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I have been treated with hormone therapy for my advanced disease for at least 6 months.

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I have advanced disease and my first treatment was AI + CDK4/6 Inhibitor, but not exemestane.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am on medication that cannot be changed and is sensitive to OATP1B1/B3.

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I have been treated with a SERD before.

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I have brain metastases.

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I do not have any active, untreated infections.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline and one assessment in cycle 1 on day 11 to 15 (each cycle is 28 days)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline and one assessment in cycle 1 on day 11 to 15 (each cycle is 28 days)

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline and one assessment in cycle 1 on day 11 to 15 (each cycle is 28 days) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose Limiting Toxicities (DLTs)

Objective Response Rate (ORR)

Secondary study objectives

AUC0-24 of abemaciclib after repeated dose administration

AUC0-24 of abemaciclib after single dose

AUC0-24 of alpelisib after repeated dose administration

+39 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: Amcenestrant/Palbociclib: Arm #2 Part C Dose Escalation, Part D Dose ExpansionExperimental Treatment2 Interventions

Part C: Amcenestrant will be administered in combination with palbociclib: amcenestrant starting oral daily dose will be one dose level below monotherapy RD and palbociclib will be dosed at fixed standard dose. Administration of higher dose of amcenestrant (with standard palbociclib dose) to subsequent participants will be based on occurrence of DLTs at initial and subsequent doses, until MAD of amcenestrant is reached. Drugs will be administered in a 28-day cycle (palbociclib will be administered for 21 days of cycle). Part D: Based on the results in Part C, participants will be administered either: 1) a determined amcenestrant dose (RD) with standard dose of palbociclib in combination therapy, or 2) one of two randomized dose levels of amcenestrant with standard dose of palbociclib in combination therapy. Drugs will be administered in a 28-day cycle (palbociclib will be administered for 21 days of cycle).

Group II: Amcenestrant/Everolimus: Arm #4 Part H Dose Escalation, Part I Dose ExpansionExperimental Treatment2 Interventions

Part H: Amcenestrant will be administered at the determined RD in combination with 2 dose levels of everolimus. Additional dose levels of amcenestrant with everolimus could be explored if needed based on the safety and PK results. Both amcenestrant and everolimus will be administered in a 28-day cycle. Part I: Based on the conclusion in Part H, participants will be administered the determined RD of amcenestrant and RD of everolimus given in the combination in an expansion cohort. Both study drugs will be administered in a 28-day cycle.

Group III: Amcenestrant/Alpelisib: Arm #3 Part F Safety Run-In, Part G Dose ExpansionExperimental Treatment2 Interventions

Part F: Amcenestrant will be administered in combination with alpelisib at a fixed standard dose. Additional dose levels of amcenestrant with alpelisib could be explored if needed based on the safety and PK results. Lower dose of alpelisib could be explored based on the PK results and safety profile from the initial combination administration. Both amcenestrant and alpelisib will be administered in a 28-day cycle. Part G: Based on the conclusion in Part F, participants will be administered the determined RD of amcenestrant and alpelisib given in the combination in an expansion cohort. Both study drugs will be administered in a 28-day cycle.

Group IV: Amcenestrant/Abemaciclib: Arm #5 Part J Dose Escalation, Part K Dose ExpansionExperimental Treatment2 Interventions

Part J: Amcenestrant will be administered at the determined RD in combination with 2 dose levels of abemaciclib. Additional dose levels of amcenestrant with abemaciclib could be explored if needed based on the safety and PK results. Both amcenestrant and abemaciclib will be administered in a 28-day cycle. Part K: Based on the conclusion in Part J, participants will be administered the determined RD of amcenestrant and RD of abemaciclib given in the combination in an expansion cohort. Both study drugs will be administered in a 28-day cycle.

Group V: Amcenestrant Monotherapy: Arm #1 Part A Dose Escalation, Part B Dose ExpansionExperimental Treatment1 Intervention

Part A: Amcenestrant will be administered orally once daily (QD). Treatment will begin with an identified starting dose. Administration of higher doses to subsequent participants is based on occurrence of DLTs and evaluation of target saturation and PK parameters at initial and subsequent doses, until maximum administered dose (MAD) is reached. Drug will be administered in a 28-day cycle. Part B: When the dose escalation phase ends, the recommended dose will be administered for the expansion cohort. Drug will be administered in a 28-day cycle.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Alpelisib

2018

Completed Phase 3

~960

Everolimus

2010

Completed Phase 4

~1510