A Multicenter, Randomized, Double-Blind, Double-Dummy, Phase III Study to Evaluate the Efficacy and Safety of Letrozole SIE Compared to Femara® (both in Combination with the CDK4/6 Inhibitor Ribociclib) in Postmenopausal Women with HR-Positive, HER2-Negative, Inoperable Locally Advanced or Metastatic Breast Cancer (SIE-3)

Condition studied

​​HR-positive, HER2-negative, inoperable locally advanced or metastatic breast cancer​

Investigational medicinal product(s)

Every trial of Ribociclib and Letrozole across our registers →

Eligibility

Primary endpoint

​PFS per Investigator assessment, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed via a local radiology assessment according to RECIST v1.1. PFS as assessed through a blinded independent central review will be used for supportive evidence of the primary efficacy endpoint.

Endpoint detail

​OS, defined as the time from the date of randomization to date of death from any cause., ​ORR defined as the proportion of participants with a BOR of CR or PR by Investigator assessment per RECIST v1.1 criteria., ​The incidence rate of a combined event of arthralgia/arthritis and/or myalgia., • TTR, defined for those participants with response (CR or PR) by Investigator assessment per RECIST v1.1 criteria as the interval between randomization and the earliest documentation of response. • DOR, defined for those participants with response (CR or PR) as the time from first documented evidence of CR or PR until disease progression by Investigator assessment per RECIST v1.1 criteria, or death from any cause, whichever occurs first., • CBR, defined as the proportion of participants with CR, PR, or SD ≥ 6 months according to Investigator assessment per RECIST v1.1 criteria. • TTF, defined as the time from randomization to study intervention discontinuation for any reason., • FACT-B. • FACT-ES. • FACT-G. • FACT-G subscales. • FACT-ES Endocrine symptoms subscale. • FACT-B Breast cancer subscale. • Time to deterioration in quality of life, as measured by these scales, • Percentage of participants with ESR1 mutations at the time of disease progression among those without ESR1 mutations at baseline. • ESR1 mutant allele frequency at the time of disease progression., • Incidence of AEs (type, severity, seriousness, and relationship to study intervention) including the incidence of TEAEs, the incidence of serious TEAEs, and the incidence of TEAEs leading to study intervention discontinuation. • Incidence of injection site reactions. • Changes in injection-related pain score assessed by NRS. • Changes in BMD assessed by DXA.