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

This is an international, multicenter, randomized, double-blind, active-controlled, phase 3 clinical trial. The purpose of this trial is to compare the efficacy and safety of palazestrant in combination with ribociclib +letrozole -matching placebo (Arm A: investigational arm) with letrozole in combination with ribociclib + palazestrant-matching placebo (Arm B: control arm).

This trial is seeking adult participants with ER+, HER2- advanced breast cancer who have not received prior systemic anti-cancer treatment for advanced disease. Approximately 1,000 participants will be randomized in a 1:1 ratio to one of the two study arms.

Primary Outcome Measures

1. Progression-Free Survival (PFS)
   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.

Secondary Outcome Measures

1. Overall Survival (OS)
   To compare OS between investigational and control arms.
2. Progression Free Survival (PFS)
   To evaluate PFS based on Blinded Independent Review Committee (BIRC) assessment
3. Overall response Rate (ORR)
   To evaluate ORR based on Blinded Independent Review Committee (BIRC) assessment
4. Duration of Response (DOR)
   To evaluate DOR based on Blinded Independent Review Committee (BIRC) assessment
5. Clinical Benefit Rate (CBR)
   To evaluate CBR based on Blinded Independent Review Committee (BIRC) assessment
6. Overall response Rate (ORR)
   To evaluate ORR based on local investigator assessment
7. Duration of Response (DOR)
   To evaluate DOR based on local investigator assessment
8. Clinical Benefit Rate (CBR)
   To evaluate CBR based on local investigator assessment
9. Safety and tolerability
   To evaluate safety and tolerability assessed by AEs, SAEs, dose modifications, clinical laboratory parameters, ECGs, performance status and vital sign measurements
10. Pharmacokinetics (PK) of palazestrant and ribociclib
    To evaluate plasma levels of palazestrant and ribociclib to establish pharmacokinetic (PK) parameters
11. Health-related patient-reported outcomes (PROs)
    To evaluate the change from baseline in health-related PROs assessed using standardized instruments that are widely used in (breast) cancer clinical trials