Vepdegestrant (ARV-471/PF-07850327) + Palbociclib vs Letrozole +

Resolution Criteria Trial: NCT05909397 Selected endpoint key: 3ff3e0df129d3973858cf6e1426cc6caff0207dd29c7517815dbefe5ab0d0bb2 Selected endpoint: Phase 3: Progression-Free Survival Endpoint type: PFS Protocol outcome group: primary Endpoint description: 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. Endpoint timeframe: From randomization date, every 12 weeks, to date of first documentation of progression or death, up to approximately 4 years. ClinicalTrials.gov population: Participants with ER-positive/HER2-negative advanced breast cancer receiving first-line treatment in the randomized Phase 3 portion Market population: Participants with ER-positive/HER2-negative advanced breast cancer receiving first-line treatment in the randomized Phase 3 portion Analysis set: Randomized Phase 3 population; the exact statistical analysis set is not specified in the enumerated outcome Comparison: Vepdegestrant plus palbociclib versus letrozole plus palbociclib Success direction: superiority Success rule: Progression-free survival, defined from randomization to first documented tumor progression determined by blinded independent central review under RECIST version 1.1 or death from any cause, whichever occurs first, must favor vepdegestrant plus palbociclib over letrozole plus palbociclib and meet the prespecified statistical success criterion in the randomized Phase 3 population. ClinicalTrials.gov source: https://clinicaltrials.gov/study/NCT05909397?tab=researcher#outcome-measures:~:text=Phase%203%3A%20Progression-Free%20Survival YES 1. The exact selected endpoint (Phase 3: Progression-Free Survival) satisfies the approved success rule in the specified population, analysis set, comparison, and timepoint. 2. The result is supported by a qualifying source in the approved evidence hierarchy. NO 1. The exact selected endpoint (Phase 3: Progression-Free Survival) misses its approved success rule. 2. No qualifying disclosure of the selected endpoint is available by 2026-12-30 at 23:59:59 UTC. NO DECISION / ADMIN REVIEW 1. Available evidence is contradictory, incomplete, pooled, interim, subgroup-only, or does not match the approved population, analysis set, comparison, and timepoint. Resolution deadline: 2026-12-30T23:59:59Z Deadline evidence: ClinicalTrials.gov identifies 2026-12-30 as the exact primary-completion date and market deadline. Deadline evidence source: https://clinicaltrials.gov/study/NCT05909397 Evidence precedence 1. ClinicalTrials.gov posted results 2. Sponsor regulatory filing or official release 3. Peer-reviewed publication or official conference abstract Only the selected endpoint in the specified population, analysis set, comparison, and timeframe can resolve YES. Overall positive messaging, another endpoint, interim results, pooled analyses, or an unmatched subgroup cannot resolve YES.