# FOURLIGHT-1

Source: https://onco.cc/trials/fourlight-1/  
OnCo record `fourlight-1` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT06105632
- Phase: 2
- Setting: HR+/HER2- advanced breast cancer after CDK4/6 inhibitor: atirmociclib + fulvestrant vs fulvestrant
- Sponsor: Pfizer
- Enrolled: 333
- Result: PFS improved (HR not yet published in detail).
- Outcomes: Progression-free survival (investigator-assessed): Atirmociclib + fulvestrant vs Fulvestrant, or everolimus + exemestane, HR 0.6
- 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.

## Sources

- ClinicalTrials.gov NCT06105632: https://clinicaltrials.gov/study/NCT06105632
- Pfizer release: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-topline-phase-2-results-next

## Connected records

- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/)
- technologies: [CDK4/6 inhibitors](https://onco.cc/technologies/cdk46-inhibitor/)
- targets: [CDK4/6](https://onco.cc/targets/cdk4-6/)
- drugs: [Atirmociclib](https://onco.cc/drugs/atirmociclib/)
- companies: [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/)
- ideas: [CDK4-selective inhibitors as the new first-line backbone](https://onco.cc/ideas/idea-cdk4-selective-first-line/)
- roadmaps: [Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test](https://onco.cc/roadmaps/hormonal-therapy-roadmap/)

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