Breast Cancer Research Foundation

Primary Outcome Measures :

1. Progression-free survival (PFS) assessed by IRC (Independent Review Committee) [ Time Frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 3 years. ]Progression-free survival (PFS) assessed by IRC (Independent Review Committee)

2. Description: PFS is defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on blinded independent central review assessment according to RECIST 1.1.

Secondary Outcome Measures :

1. PFS assessed by INVs (Investigators) [ Time Frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 3 years. ]PFS is defined as the time from randomization to progression of tumor as assessed by INVs or death from any cause on study.

2. Time to CNS PFS assessed by IRC [ Time Frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 3 years. ]Defined as earlier event of CNS progression or death based on blinded independent central review assessment according to RECIST 1.1.

3. Overall survival (OS) [ Time Frame: From baseline until death due to any cause; up to a maximum of approximately 4 years. ]OS is defined as the time from the date of randomization until death due to any cause.

4. Objective response rate (ORR) [ Time Frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 4 years. ]Defined as the number (%) of patients with measurable disease with at least 1 visit response of CR (Complete response) or PR (Partial response) based on blinded independent central review assessment according to RECIST 1.1.

5. Duration of response (DoR) [ Time Frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 4 years. ]Defined as the time from the date of first documented response (i.e., subsequently confirmed) until the date of documented progression or death in the absence of disease progression based on blinded independent central review assessment according to RECIST 1.1.

6. Disease control rate (DCR) [ Time Frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 4 years. ]Defined as Disease control rate is defined as the percentage of subjects who have a best overall response of CR or PR or SD based on blinded independent central review assessment according to RECIST 1.1.

7. Time to death or distant metastases (TTDM) [ Time Frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression; up to a maximum of approximately 4 years. ]Defined as the time from the date of randomization until the first date of distant metastasis or date of death in the absence of distant metastasis based on blinded independent central review assessment according to RECIST 1.1

8. Incidence of Adverse Events (AEs) [ Time Frame: From the screening period to 28 days after treatment completion, approximately 4 years. ]AEs are graded according to CTCAE v5.0 and recorded in the case report form.