Vepdegestrant

It is defined as the number of participants with Grade 4 neutropenia AE (graded by NCI CTCAE v.5.0) with onset within the first 4 cycles divided by the number of participants.

It is defined as the number of participants reducing the dose of palbociclib and/or vepdegestrant due to any cause occurring within the first 4 cycles divided by the number of participants.

It is defined as the number of participants discontinuing palbociclib and/or vepdegestrant due to any cause occurring within the first 4 cycles divided by the number of participants.

Progression-free survival is defined as the time interval from the date of randomization to the date of first documented tumor progression determined by Blinded Independent Central Review (BICR) as per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) or death due to any cause, whichever come first.

PFS assessed by BICR was defined as the time from the date of randomization to the date of the first documentation of objective progression of disease (PD) per RECIST v1.1, or death due to any cause, whichever occurred first. PD as per RECIST v1.1 was defined as at least a 20% increase in the sum of diameters of target measurable lesions above nadir (smallest sum observed considering baseline and all assessments prior to the timepoint under evaluation), with a minimum absolute increase of 5 millimeters (mm) relative to nadir or unequivocal progression of existing non-target lesions or the presence of new lesions. PFS was censored on the date of last adequate disease assessment for those who did not have a PFS event, discontinued the study treatment due to withdrawal of consent prior to an event, started a new anticancer therapy prior to an event, had an event after a gap of 2 or more missing disease assessments, or lost to follow-up. Kaplan-Meier method was used.

PFS assessed by BICR was defined as the time from the date of randomization to the date of the first documentation of objective PD per RECIST v1.1, or death due to any cause, whichever occurred first. PD as per RECIST v1.1 was defined as at least a 20% increase in the sum of diameters of target measurable lesions above nadir (smallest sum observed considering baseline and all assessments prior to the timepoint under evaluation), with a minimum absolute increase of 5 mm relative to nadir or unequivocal progression of existing non-target lesions or the presence of new lesions. PFS was censored on the date of last adequate disease assessment for those who did not have a PFS event, discontinued the study treatment due to withdrawal of consent prior to an event, started a new anticancer therapy prior to an event, had an event after a gap of 2 or more missing disease assessments, or lost to follow-up. Kaplan-Meier method was used.

Hematological DLT: neutropenic fever; Grade\>=3 thrombocytopenia associated with Grade\>=2(clinically significant)bleeding and Grade4 neutropenia/thrombocytopenia lasting \<7 days. Non-hematological: Grade\>=3 toxicities clinically significant,except those that were not been maximally treated;Grade 2 aspartate aminotransferase(AST), alanine aminotransferase(ALT)/alkaline phosphatase(ALP) levels at baseline as result of liver/bone metastasis,AST,ALT and ALP level\>8\*baseline/AST/ALT \>5\*baseline for\>=14 days; Hy's Law(concomitant ALT/AST elevation of \>=3\*upper limit of normal \[ULN\], total bilirubin elevation\>=2\*ULN without clear alternative etiology); Grade≥3 electrolyte abnormality with clinical sequelae; QTcF prolongation:any Grade\>=3 QT prolongation without clear alternative etiology;any adverse event (AE) attributed to Vepdegestrant and/or PF-07220060 resulting in failure to deliver 75% of doses for either/both agents and any death not clearly due to underlying disease/extraneous causes.

OR was defined as best overall response (BOR) of confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors (RECIST) version (v) 1.1. CR was defined as complete disappearance of all target lesions, except for nodal disease, complete disappearance of all non-target lesions and no new lesions. All nodes, both target and non-target, must decrease to normal (short axis \<10 millimeter \[mm\]). PR was defined as at least a \>=30% decrease from baseline in the sum of diameters of all target lesions. The short diameter was used in the sum for nodal target lesions, while the longest diameter was used in the sum for non-nodal target lesions, all target lesions were assessed.

Dose Limiting Toxicities rate for ARV-471 in combination with Samuraciclib, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1).

Steady-state Area under the plasma concentration versus time curve (AUCtau) of ARV-471 with and without coadministration of samuraciclib

Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. as determined by investigator assessment.

Single dose AUC0-72 of samuraciclib with and without coadministration of ARV 471.

Exposure (AUCtau) of ribociclib with and without co-administration of ARV-471

Concentration (Cmax) of ribociclib with and without co-administration of ARV-471

Maximum plasma concentration

Area under the concentration-time profile from time zero to time tau (τ), the dosing interval, where tau = 24 hours (QD dosing)

Maximum Observed Plasma Concentration (Cmax)

Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.

DLT was defined as any adverse event (AE) or abnormal laboratory value which were related to ARV-471 and assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies occurring during the first 28 days of treatment that met at least 1 of the study specified criteria.