Phase IIIb Study of Ribociclib + ET in Early Breast Cancer

The study consists of Screening, Treatment, and Follow-up periods.

• Treatment Period: all participants who complete screening will receive ribociclib 400 mg orally once daily on days 1 to 21 of a 28-day cycle, in combination with daily ET for 36 months (approximately 39 cycles) from the date of first dose. The Treatment Period starts when the patient receives their first dose of ribociclib and ends at the time of the 30-day Safety Follow-up. All treated participants should have a Safety Follow-up call conducted 30 days after the last dose of study treatment.
• Follow-up period: participants will be followed from 30 days after study treatment (i.e., ribociclib) completion/discontinuation (i.e. 30-day Safety Follow-up) until death, withdrawal of consent, lost to follow-up, or until 48 months after the last participant has received their first dose of study treatment (i.e. End of Study \[EOS\]), whichever occurs first.

Participants will receive ribociclib 400 mg orally once daily on days 1 to 21 of a 28-day cycle, in combination with daily endocrine therapy (ET) for 36 months (approximately 39 cycles). ET consists of:

• For postmenopausal women: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously.
• For pre/perimenopausal women, and men: letrozole 2.5 mg orally once daily continuously, anastrozole 1 mg orally once daily continuously, or exemestane 25 mg once daily continuously, combined with goserelin subcutaneously (at 3.6 mg once every 4 weeks if the one-month depot formulation is used or at 10.8 mg once every 3 months if the three-month depot formulation is used) or leuprolide subcutaneously (at 3.75 mg once every 4 weeks if the one-month depot formulation is used or at 11.25 mg once every 3 months if the three-month depot formulation is used)

Drug: Ribociclib · Drug: Letrozole · Drug: Ansastrozole · Drug: Goserelin · Drug: Leuprolide · Drug: Exemestane

Ribociclib 400 mg orally once daily on days 1-21 of a 28 day cycle followed by 7 days rest

Letrozole 2.5 mg orally once daily continuously

Anastrozole 1 mg orally once daily continuously.

Goserelin administered subcutaneously at 3.6 mg once every 4 weeks if the one-month depot formulation is used or at 10.8 mg once every 3 months if the three-month depot formulation is used

Leuprolide administered subcutaneously at 3.75 mg once every 4 weeks if the one-month depot formulation is used or at 11.25 mg once every 3 months if the three-month depot formulation is used

Exemestane 25 mg once daily continuously

Plazo: At 3 years

iBCFS is defined as the time from the date of first dose to the date of the first event of invasive ipsilateral breast tumor recurrence, local/regional invasive recurrence, distant recurrence, death (any cause), or contralateral invasive BC. iBCFS will be assessed using STEEP criteria version 2.0 (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials), as assessed by Investigator.

The iBCFS rate at 3 years will be assessed.

Plazo: Up to approximately 6 years

To evaluate Safety of ribociclib + ET

Plazo: Up to approximately 6 years

iDFS is defined as the time from the date of first dose of study treatment to the date of the first event of invasive ipsilateral breast tumor recurrence, local/regional invasive recurrence, distant recurrence, death (any cause), contralateral invasive BC, or second primary non-breast invasive cancer (excluding basal and squamous cell carcinomas of the skin). iDFS will be assessed using STEEP 2.0 as assessed by the investigator.

Plazo: Up to approximately 6 years

Distant Disease-Free Survival (DDFS) is defined as the time from the date of first dose of study treatment to the date of the first event of recurrence at a distant site, death (any cause), or second primary non-breast invasive cancer (excluding in situ/non-invasive cancers and basal and squamous cell carcinomas of the skin).

DDFS will be assessed using STEEP 2.0 as assessed by the investigator.

Plazo: Up to approximately 6 years

Distant Relapse Free Survival (DRFS) is defined as the time from the date of first dose of study treatment to the date of the first event of recurrence at a distant site or death (any cause). DRFS will be assessed using STEEP 2.0 as assessed by the investigator.

Plazo: Up to approximately 6 years

RFI is defined as the time from date of first dose to date of first event of invasive recurrence in the ipsilateral breast or locoregionally, at a distant site, or death from breast cancer. RFI will be assessed using STEEP 2.0 as per investigator assessment.

Plazo: Up to 3 years

RDI is defined as the ratio of the dose intensity delivered to the planned dose intensity.

Plazo: Up to approximately 6 years

OS is defined as time from the start of study treatment to date of death due to any cause.

Plazo: Up to 3 years

TTD is defined as the time from starting ribociclib to the time to treatment discontinuation due to any cause.

Plazo: Up to approximately 6 years

The FACT-B is a questionnaire that consists of 37 items with items from FACT-General (FACT-G) questionnaire (27 items) and from the Breast Cancer Subscale (BCS, 10 items). FACT-B consists of five subscales that address different aspects of the participant's quality of life: physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and BCS.

Plazo: Up to approximately 6 years

The FACT-ES is a questionnaire that consists of 19 items which assesses endocrine complaints and adverse events.

Plazo: Up to approximately 6 years

The FACIT-F is a 13-item questionnaire designed to assess self-reported fatigue and its impact on daily activities and functions.

Plazo: Up to approximately 6 years

EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D-5L health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

Plazo: Up to approximately 6 years

WPAI-GH measures the impact of health problems on the participant's productivity, in paid or unpaid activities, in the last 7 days. It is 6-item scale measuring absenteeism, presenteeism, and impairments in unpaid activity.

A Phase IIIb Study to Characterize the Efficacy and Safety of Adjuvant Ribociclib Plus Endocrine Therapy in a Close-to-clinical Practice Patient Population With HR+ HER2- Early Breast Cancer (Adjuvant WIDER)