Pfizer Inc. (NYSE: PFE) today announced positive topline results from the randomized Phase 2 FOURLIGHT-1 study evaluating atirmociclib in combination with fulvestrant, versus fulvestrant or everolimus plus exemestane, in people with hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (MBC) who had received prior cyclin-dependent kinase (CDK) 4/6 inhibitor-based treatment. The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) as assessed by the investigator [HR: 0.60 (95% CI: (0.440, 0.825)), p=0.0007].
The PFS results were consistent across all prespecified subgroups, including performance status, menopausal status, presence of visceral disease, duration of treatment with prior CDK4/6 inhibitor (< or > 12 months), and regardless of prior CDK4/6 inhibitor received. More than 90% of patients initiated treatment with atirmociclib within three months of their last CDK4/6 inhibitor treatment. Overall survival (OS), a secondary endpoint, was not mature at the time of the analysis, with approximately 20% of participants having an event. These are the first randomized Phase 2 data in HR+ MBC for atirmociclib, an investigational, potential first-in-class CDK4 inhibitor.
"These results are especially encouraging given that the FOURLIGHT‑1 study enrolled patients whose disease had progressed soon after prior CDK4/6 inhibitor therapy, a difficult-to-treat population," said Jeff Legos, Chief Oncology Officer, Pfizer. "The strength of these data reinforces our confidence that atirmociclib may meaningfully differentiate from the CDK4/6 inhibitor class, the standard-of-care backbone in HR-positive breast cancer, with the potential for improved efficacy and tolerability. We are continuing to accelerate development of this next-generation cell cycle inhibitor in earlier lines of therapy where it may offer even greater benefit for patients."
In FOURLIGHT-1, atirmociclib demonstrated manageable safety and was well tolerated, with 6.4 percent of patients discontinuing atirmociclib due to treatment-emergent adverse events. Its safety profile was consistent with prior studies, and no new safety signals were identified. Detailed results will be submitted for presentation at a future medical meeting.
These findings support Pfizer's strategy to advance atirmociclib in first-line and early-stage disease, where durable endocrine-based control has the potential to have the greatest impact. A Phase 3 registrational study for atirmociclib in the first-line metastatic setting is ongoing and results from a Phase 2 neoadjuvant study in early breast cancer will be shared at a future medical meeting.
About the FOURLIGHT-1 Trial
FOURLIGHT-1 (NCT06105632) is an interventional, open-label, randomized, multicenter Phase 2 study evaluating atirmociclib plus fulvestrant compared with fulvestrant or everolimus plus exemestane, in adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (MBC). The trial enrolled 264 patients in 14 countries whose disease progressed after cyclin-dependent kinase (CDK) 4/6 inhibitor-based treatment. The primary endpoint was progression-free survival (PFS) as determined by investigator assessment. Secondary endpoints include overall survival, objective response, duration of response and clinical benefit response.
About Atirmociclib
Atirmociclib is an investigational oral inhibitor of cyclin-dependent kinase 4 (CDK4), a key regulator of the cell cycle that triggers cellular progression. It was conceptualized and discovered at Pfizer and is being developed for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative (HER2-) breast cancer.
About Pfizer Oncology
At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and multispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world's most common cancers, including breast cancer, gastrointestinal cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.
