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

• ClinicalTrials.gov Identifier: NCT04478266
• Recruitment Status: Recruiting
• First Posted: July 20, 2020
• Last Update Posted: June 7, 2021
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: July 10, 2020
• First Posted Date: July 20, 2020
• Last Update Posted Date: June 7, 2021
• Actual Study Start Date: October 14, 2020
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 19, 2021)

Progression-free survival [ Time Frame: From randomization date to date of first documentation of progression OR death (up to approximately 4 years) ]

Progression-free survival is defined as the time interval from the date of randomization to the date of first documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or death (due to any cause), whichever come first.

Original Primary Outcome Measures (submitted: July 15, 2020)

Progression-free survival [ Time Frame: From randomization date to date of first documentation of progression OR death (up to approximately 3.5 years) ]

Progression-free survival is defined as the time interval from the date of randomization to the date of first documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or death (due to any cause), whichever come first.

Current Secondary Outcome Measures (submitted: February 19, 2021)

• Overall Survival [ Time Frame: From randomization date to date of death (up to approximately 6 years) ]
  Overall survival is defined as the time interval from the date of randomization to the date of documented death (due to any cause).
• Objective Response Rate [ Time Frame: From randomization date to end of treatment (up to approximately 4 years) ]
  Objective response rate is defined as the proportion of participants who have a CR or PR, as best overall response determined as per RECIST 1.1, from the date of randomization to the date of until disease progression, death, cutoff date, initiation of post-treatment anti-cancer therapy, whichever occurs first.
• Duration of Response [ Time Frame: From randomization date to end of treatment (up to approximately 4 years) ]
  Duration of response is defined as the time from first documented evidence of CR or PR until progressive disease (PD) as determined as per RECIST 1.1 or death from any cause, whichever occurs first.
• Clinical Benefit Rate [ Time Frame: From randomization date to end of treatment (up to approximately 4 years) ]
  Clinical benefit rate is defined as the proportion of participants who have a confirmed CR, PR, or SD for at least 24 weeks determined as per RECIST 1.1, from the date of randomization until disease progression, death, cutoff date, initiation of post-treatment anti-cancer therapy, whichever occurs first
• PK parameter: Plasma concentrations [ Time Frame: From randomization date to end of treatment (up to approximately 4 years) ]
  Plasma concentrations of Amcenestrant and palbociclib.
• Number of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) [ Time Frame: From Baseline up to end of study (approximately 6.5 years) ]
  Incidence of participants with TEAEs, SAEs and laboratory abnormalities according to NCI CTCAE V5
• Time to First Chemotherapy [ Time Frame: From randomization date to end of treatment (up to approximately 4 years) ]
  Time to chemotherapy is defined as the time interval from the date of randomization to the start date of the first chemotherapy after study treatment discontinuation.
• Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L) [ Time Frame: From Baseline to 90 days after end of treatment (up to approximately 4 years) ]
  Change From Baseline between treatment comparison Using the European Quality of Life- 5-Dimension 5 Level (EQ-5D 5L).
• Disease-specific HRQL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30) [ Time Frame: From Baseline to 90 days after end of treatment (up to approximately 4 years) ]
  Change From Baseline between treatment comparison in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30).
• Disease- and treatment-related quality of life will be assessed using the EORTC breast cancer module (QLQ-BR45) questionnaire [ Time Frame: From Baseline to 90 days after end of treatment (up to approximately 4 years) ]
  Change From Baseline between treatment comparison in Quality of Life Using the EORTC QLQ-BR45 (Breast) Questionnaire.
• Disease- and treatment-related quality of life will be assessed using the EORTC breast cancer module (QLQ-BR23) questionnaire [ Time Frame: From Baseline to 90 days after end of treatment (up to approximately 4 years) ]
  Change From Baseline between treatment comparison in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire.
• Progression-free survival on next line of therapy (PFS2) [ Time Frame: From randomization date to date of death (up to approximately 6.5 years) ]
  PFS2 is defined as the time from the date of randomization to the date of first documentation of PD on the next systemic anti-cancer therapy according to investigator or death due to any cause, whichever occurs first.

Original Secondary Outcome Measures (submitted: July 15, 2020)

• Overall Survival [ Time Frame: From randomization date to date of death (up to approximately 6 years) ]
  Overall survival is defined as the time interval from the date of randomization to the date of documented death (due to any cause).
• Objective Response Rate [ Time Frame: From randomization date to end of treatment (up to approximately 3.5 years) ]
  Objective response rate is defined as the proportion of participants who have a CR or PR, as best overall response determined as per RECIST 1.1, from the date of randomization to the date of until disease progression, death, cutoff date, initiation of post-treatment anti-cancer therapy, whichever occurs first.
• Duration of Response [ Time Frame: From randomization date to end of treatment (up to approximately 3.5 years) ]
  Duration of response is defined as the time from first documented evidence of CR or PR until progressive disease (PD) as determined as per RECIST 1.1 or death from any cause, whichever occurs first.
• Clinical Benefit Rate [ Time Frame: From randomization date to end of treatment (up to approximately 3.5 years) ]
  Clinical benefit rate is defined as the proportion of participants who have a confirmed CR, PR, or SD for at least 24 weeks determined as per RECIST 1.1, from the date of randomization until disease progression, death, cutoff date, initiation of post-treatment anti-cancer therapy, whichever occurs first.
• PK parameter: Plasma concentrations [ Time Frame: From randomization date to end of treatment (up to approximately 3.5 years) ]
  Plasma concentrations of SAR439859, goserelin and palbociclib
• Change From Baseline between treatment comparison Using the European Quality of Life- 5-Dimension 5 Level (EQ-5D 5L) [ Time Frame: From Baseline to 90 days after end of treatment (up to approximately 3.5 years) ]
  Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L).
• Change From Baseline between treatment comparison in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) [ Time Frame: From Baseline to 90 days after end of treatment (up to approximately 3.5 years) ]
  Disease-specific HRQL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30).
• Change From Baseline between treatment comparison in Quality of Life Using the EORTC QLQ-BR45 (Breast) Questionnaire [ Time Frame: From Baseline to 90 days after end of treatment (up to approximately 3.5 years) ]
  Disease- and treatment-related quality of life will be assessed using the EORTC breast cancer module (QLQ-BR45) questionnaire.
• Time to First Chemotherapy [ Time Frame: From randomization date to end of treatment (up to approximately 3.5 years) ]
  Time to chemotherapy is defined as the time interval from the date of randomization to the start date of the first chemotherapy after study treatment discontinuation.
• Number of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) [ Time Frame: From Baseline up to end of study (approximately 6 years) ]
  Incidence of participants with TEAEs, SAEs and laboratory abnormalities according to NCI CTCAE V5

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Amcenestrant (SAR439859) Plus Palbociclib as First Line Therapy for Patients With ER (+) HER2(-) Advanced Breast Cancer
• Official Title: 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

Brief Summary

Primary Objective:

To determine whether Amcenestrant (SAR439859) in combination with palbociclib improvesprogression free survival (PFS) when compared with letrozole in combination with palbociclib in participants with ER+, 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

• Detailed Description: Study duration per participant is approximately 64 months, which includes a 33- month treatment period
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Drug: Amcenestrant-matching placebo
  Pharmaceutical form: Tablets Route of Administration: Oral
• Drug: SAR439859
  Pharmaceutical form: Tablets Route of Administration: Oral
  Other Name: Amcenestrant
• Drug: Palbociclib
  Pharmaceutical form: Capsules/Tablets Route of Administration: Oral
  Other Name: Ibrance
• Drug: Letrozole
  Pharmaceutical form: Tablets Route of Administration: Orally
• Drug: Goserelin
  Pharmaceutical form: Depot Injection Route of Administration: Subcutaneous
• Drug: Letrozole-matching placebo
  Pharmaceutical form: Tablets Route of Administration: Orally

Study Arms

• Experimental: Amcenestrant with Letrozole-matching placebo Arm
  Participants in Amcenestrant with Letrozole-matching placebo Arm will be administered: Amcenestrant dose, once daily, continuously. Letrozole-matching placebo, once daily, continuously. Palbociclib dose once daily, days 1-21 of every 28-day cycle. Goserelin once every 4 weeks in pre/peri menopausal women and men
  Interventions:

  • Drug: SAR439859
  • Drug: Palbociclib
  • Drug: Goserelin
  • Drug: Letrozole-matching placebo
• Active Comparator: Letrozole with Amcenestrant matching placebo Arm
  Participants in Letrozole with Amcenestrant-matching placebo Arm will be administered: Letrozole dose, once daily, continuously. Amcenestrant-matching placebo, once daily, continuously. Palbociclib dose once daily, days 1-21 of every 28-day cycle Goserelin once every 4 weeks in pre/peri menopausal women and men
  Interventions:

  • Drug: Amcenestrant-matching placebo
  • Drug: Palbociclib
  • Drug: Letrozole
  • Drug: Goserelin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 19, 2021): 1066
• Original Estimated Enrollment (submitted: July 15, 2020): 708
• Estimated Study Completion Date: August 2027
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Eligibility 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 child bearing 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 is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada); 800-633-1610 ext option 6; Contact-US@sanofi.com

• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Czechia, Estonia, Finland, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Puerto Rico, Russian Federation, Singapore, Spain, Taiwan, Turkey, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT04478266
• Other Study ID Numbers: EFC15935; 2020-001824-33 ( EudraCT Number ); U1111-1233-0486 ( Other Identifier: UTN )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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://www.clinicalstudydatarequest.com/

• Responsible Party: Sanofi
• Study Sponsor: Sanofi
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: June 2021