{"entity":{"id":"fourlight-1","kind":"trial","name":"FOURLIGHT-1","aka":[],"tldr":"In FOURLIGHT-1, a CDK4-only inhibitor designed to avoid the low blood counts of current CDK4/6 drugs improved progression-free survival in second line.","summary":"FOURLIGHT-1, trial NCT06105632 sponsored by Pfizer and reported in early 2026, showed in a randomised phase 2 that atirmociclib, a CDK4-only inhibitor designed to avoid the low blood counts of current CDK4/6 drugs, improves progression-free survival when added to fulvestrant after progression on a CDK4/6 inhibitor in HR-positive, HER2-negative advanced breast cancer. The trial, which enrolled 333 patients according to ClinicalTrials.gov, met its primary endpoint in topline results on 17 March 2026 with lower neutropenia than dual CDK4/6 inhibitors, and the phase 3 FOURLIGHT-3 trial in the first line is enrolling. OnCo links it to CDK4/6 as a target, atirmociclib and the idea of CDK4-selective inhibitors as the new first-line backbone. It is the first randomised evidence that a selective CDK4 inhibitor works after CDK4/6 progression, and whether that holds in the first-line phase 3 is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT06105632","url":"https://clinicaltrials.gov/study/NCT06105632"},{"label":"Pfizer release","url":"https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-topline-phase-2-results-next"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["cdk46-inhibitor"],"targets":["cdk4-6"],"drugs":["atirmociclib"],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT06105632","phase":"2","setting":"HR+/HER2- advanced breast cancer after CDK4/6 inhibitor: atirmociclib + fulvestrant vs fulvestrant","sponsor":"Pfizer","result":"PFS improved (HR not yet published in detail).","started":"2024-01-09","startedType":"actual","yearReported":2026,"enrolled":333,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (investigator-assessed)","primary":true,"unit":"months","arms":[{"name":"Atirmociclib + fulvestrant","note":"Randomised phase 2, post-CDK4/6 inhibitor; medians pending presentation (topline 17 March 2026)"},{"name":"Fulvestrant, or everolimus + exemestane"}],"hr":0.6,"ci":[0.44,0.825],"p":"0.0007","source":"https://www.cancernetwork.com/view/atirmociclib-fulvestrant-improves-pfs-in-hr-her2-breast-cancer"}],"replication":"First randomised evidence that a selective CDK4 inhibitor works after CDK4/6 progression; the first-line phase 3 programme will be the confirmatory test."},"route":"/trials/fourlight-1/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"}],"technology":[{"id":"cdk46-inhibitor","kind":"technology","name":"CDK4/6 inhibitors","route":"/technologies/cdk46-inhibitor/"}],"target":[{"id":"cdk4-6","kind":"target","name":"CDK4/6","route":"/targets/cdk4-6/"}],"drug":[{"id":"atirmociclib","kind":"drug","name":"Atirmociclib","route":"/drugs/atirmociclib/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"idea":[{"id":"idea-cdk4-selective-first-line","kind":"idea","name":"CDK4-selective inhibitors as the new first-line backbone","route":"/ideas/idea-cdk4-selective-first-line/"}],"roadmap":[{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"}]}}