Palazestrant in Combination With Ribociclib for the First-line Treatment of ER+/HER2- Advanced Breast Cancer

Progression-Free Survival (PFS)

Timeframe: From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 3.5 years)

To compare PFS, based on a local investigator assessment, between investigational (palazestrant with ribociclib + letrozole-matching placebo) and control (letrozole with ribociclib + palazestrant-matching placebo) arms.

Overall Survival (OS)

Timeframe: From Date of Randomization until Death Due to Any Cause (estimated as up to 5.5 years)

To compare OS between investigational and control arms.

Progression Free Survival (PFS)

Timeframe: From Date of Randomization until Disease Progression or Death Due to Any Cause (estimated as up to 3.5 years)

To evaluate PFS based on Blinded Independent Review Committee (BIRC) assessment

Overall response Rate (ORR)

Timeframe: From Date of Randomization until Tumor Response (estimated as up to 3.5 years)

To evaluate ORR based on Blinded Independent Review Committee (BIRC) assessment

Duration of Response (DOR)

Timeframe: From Date of Tumor Response (CR or PR) until Disease Progression (estimated as up to 3.5 years)

To evaluate DOR based on Blinded Independent Review Committee (BIRC) assessment

Clinical Benefit Rate (CBR)

Timeframe: Proportion of subjects achieving CR, PR or SD with duration of at least 24 weeks (estimated as up to 3.5 years)

To evaluate CBR based on Blinded Independent Review Committee (BIRC) assessment

Overall response Rate (ORR)

Timeframe: From Date of Randomization until Tumor Response (estimated as up to 3.5 years)

To evaluate ORR based on local investigator assessment

Duration of Response (DOR)

Timeframe: From Date of Tumor Response (CR or PR) until Disease Progression (estimated as up to 3.5 years)

To evaluate DOR based on local investigator assessment

Clinical Benefit Rate (CBR)

Timeframe: Proportion of subjects achieving CR, PR or SD with duration of at least 24 weeks (estimated as up to 3.5 years)

To evaluate CBR based on local investigator assessment

Safety and tolerability

Timeframe: Up to 42 days after end of treatment (estimated as up to 3.5 years)

To evaluate safety and tolerability assessed by AEs, SAEs, dose modifications, clinical laboratory parameters, ECGs, performance status and vital sign measurements

Pharmacokinetics (PK) of palazestrant and ribociclib

Timeframe: Every 28 days (estimated as up to 3.5 years)

To evaluate plasma levels of palazestrant and ribociclib to establish pharmacokinetic (PK) parameters

Health-related patient-reported outcomes (PROs)

Timeframe: Every 28 days (estimated as up to 3.5 years)

To evaluate the change from baseline in health-related PROs assessed using standardized instruments that are widely used in (breast) cancer clinical trials