Trial: Study of PF-07220060 With Letrozole in …

Trial Details

Sponsor: Pfizer (industry)

Phase: 3

Start date: Jan. 6, 2025

Planned enrollment: 1020

Trial ID: NCT06760637

More trial details at ClinicalTrials.gov

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Investigational Drug AI Analysis

Show for: Atirmociclib (PF-07220060, Example A94)

Overview

Atirmociclib (PF-07220060; Example A94) is an investigational, orally administered, selective cyclin-dependent kinase 4 (CDK4) inhibitor developed by Pfizer. Clinical development has focused primarily on hormone receptor-positive, HER2-negative (HR+/HER2−) advanced or metastatic breast cancer, including disease that progressed during prior CDK4/6-inhibitor therapy. It has also been studied in other solid tumors and in combinations with endocrine therapy and other targeted agents. (asco.org)

Mechanism of action

CDK4–cyclin D promotes cell-cycle progression by phosphorylating retinoblastoma protein, thereby activating the E2F pathway and transition from G1 to S phase. Atirmociclib selectively inhibits CDK4, suppressing retinoblastoma phosphorylation and tumor-cell proliferation. Its greater selectivity for CDK4 over CDK6 is intended to preserve CDK6-dependent hematopoiesis and potentially reduce neutropenia relative to dual CDK4/6 inhibitors. Preclinical experiments demonstrated antitumor activity and less inhibition of hematopoietic progenitor cells, although these advantages require confirmation in comparative clinical trials. (pubmed.ncbi.nlm.nih.gov)

Efficacy

In the first-in-human phase 1/2a study (NCT04557449), 26 patients with HR+/HER2− metastatic breast cancer previously treated with a CDK4/6 inhibitor received atirmociclib plus letrozole or fulvestrant. Among 21 patients with measurable disease, the confirmed objective response rate was 28.6%—one complete and five partial responses—and the clinical-benefit rate was 52.4%. Median progression-free survival was 24.7 weeks. (asco.org)

With longer follow-up in a heavily pretreated cohort, the reported confirmed response rate was 32% (8/25 evaluable patients) and median progression-free survival was 8.1 months; these updated figures were disclosed in a company scientific presentation rather than a peer-reviewed publication. (investors.pfizer.com)

In the randomized 264-patient phase 2 FOURLIGHT-1 study, atirmociclib plus fulvestrant reduced the investigator-assessed risk of progression or death by 40% versus fulvestrant or everolimus plus exemestane (hazard ratio 0.60; 95% CI 0.440–0.825; p=0.0007). Median progression-free survival and response-rate results had not yet been publicly reported, and overall-survival data were immature. These findings were announced as topline company results on March 17, 2026 and had not yet undergone presentation or peer review. (pfizer.com)

Safety

In the phase 1/2a endocrine-therapy cohorts, the most frequent treatment-related toxicities included neutropenia, leukopenia, anemia, diarrhea and nausea. In a 39-patient fulvestrant expansion cohort, treatment-related neutropenia occurred in 38.5%, leukopenia in 33.3% and anemia in 25.6%; the most frequent grade 3 events were neutropenia and leukopenia, each in 12.8%. No grade 4 or higher treatment-related events or febrile neutropenia were reported, and no patient discontinued atirmociclib because of a treatment-related event. (pfizeroncologydevelopment.com)

In FOURLIGHT-1, 6.4% of patients discontinued atirmociclib because of treatment-emergent adverse events. Detailed event rates were not included in the topline announcement, which described the safety profile as manageable and reported no new safety signals. (pfizer.com)

TrialFetch AI Analysis

Goal: Determine whether atirmociclib (PF-07220060) plus letrozole improves efficacy while maintaining acceptable safety compared with an approved CDK4/6 inhibitor plus letrozole as first-line treatment for HR-positive, HER2-negative advanced or metastatic breast cancer.

Patients: Adults with unresectable locally advanced or metastatic HR-positive, HER2-negative breast cancer who have received no systemic therapy for advanced disease. Measurable disease or bone-only nonmeasurable disease is permitted. Key exclusions include visceral crisis, current or prior CNS metastases, and recurrence during or within 12 months of completing (neo)adjuvant endocrine therapy or a CDK4/6 inhibitor.

Design: Open-label, multicenter, randomized trial assigning participants approximately 1:1 to the investigational regimen or investigator-selected active comparator.

Treatments: The experimental arm receives oral atirmociclib plus oral letrozole. Atirmociclib selectively inhibits CDK4, aiming to suppress retinoblastoma-protein phosphorylation and cell-cycle progression while potentially reducing CDK6-related hematologic toxicity. In an early-phase study of previously CDK4/6 inhibitor–treated HR-positive, HER2-negative metastatic breast cancer, atirmociclib plus endocrine therapy produced a confirmed response rate of 28.6% among 21 patients with measurable disease; a subsequent phase 2 topline announcement reported improved progression-free survival with atirmociclib plus fulvestrant versus its comparators, but these findings do not establish benefit in this first-line setting. The comparator is investigator-selected oral palbociclib, ribociclib, or abemaciclib plus letrozole, representing established CDK4/6 inhibitor–based endocrine treatment.

Outcomes: The primary endpoint is progression-free survival by blinded independent central review using RECIST v1.1. Secondary measures include overall survival, investigator-assessed progression-free survival, objective response, duration of response, treatment-related adverse and serious adverse events, patient-reported quality of life and pain, and change in circulating tumor DNA.

Burden on patient: Likely moderate and broadly similar to routine CDK inhibitor care: both arms use oral treatment, with regular clinic visits, safety monitoring, and tumor assessments every 8 weeks for the first 48 weeks and every 12 weeks thereafter. Quality-of-life questionnaires and circulating tumor DNA sampling add some research procedures. No mandatory biopsies or intensive pharmacokinetic sampling are specified.

Last updated: Sep 2026

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Status: Not yet recruiting

Trial Details

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: Atirmociclib (PF-07220060, Example A94)

Overview

Mechanism of action

Efficacy

Safety

Further reading

TrialFetch AI Analysis

Eligibility

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Sites (518)

Princess Alexandra Hospital

Townsville University Hospital

Frankston Hospital

Peter MacCallum Cancer Centre

Rosebud Hospital

Royal Melbourne Hospital

AZORG Campus Aalst-Moorselbaan

Antwerp University Hospital

Institut Jules Bordet

Grand Hôpital de Charleroi

AZ Maria Middelares

UZ Leuven

Hospital Santa Rita de Cassia

Hospital Brasilia

Santa Casa de Misericordia de Passos

Real Hospital Portugues

Associação Hospitalar Beneficente São Vicente de Paulo

Hospital São Vicente de Paulo

ONCOSITE - Centro de Pesquisa Clinica em Oncologia

Faculdade de Medicina do ABC

Hospital Alemao Oswaldo Cruz

Complex Oncology Center - Burgas

Complex Oncology Center - Plovdiv EOOD

MHAT for Women's Health Nadezhda

Multiprofile Hospital for Active Treatment Dr. Tota Venkova AD

University Specialized Hospital for Active Treatment of Oncology EAD

Multiprofile Hospital for Active Treatment Serdikamed EOOD

Arthur J.E. Child Comprehensive Cancer Centre

Cross Cancer Institute

Dr. Everett Chalmers Regional Hospital

Princess Margaret Cancer Centre

Sunnybrook Research Institute

CIUSSS- saguenay-Lac-Saint-Jean

Jewish General Hospital

Anhui Provincial Cancer Hospital

Beijing Cancer hospital

Cancer Hospital Chinese Academy of Medical Science

Peking University People's Hospital

Fujian Medical University Union Hospital

The First Hospital of Lanzhou University

Sun Yat-sen University Cancer Center

Sun Yat-sen University Cancer Center

The First People's Hospital of Foshan

Harbin Medical University Cancer Hospital

Hubei Cancer Hospital

Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology

Wuhan Union Hospital Cancer Center

Hunan Cancer Hospital

Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School

The First Hospital of Jilin University

The 2nd Affiliated Hospital of Dalian Medical University

The First Hospital of China Medical University

The First Affiliated Hospital of Xi'an Jiaotong University

The Second Affiliated Hospital of Xi'an Jiaotong University

Shandong Cancer Hospital

Fudan University Shanghai Cancer Center

Sir Run Run Shaw Hospital

Taizhou Hospital of Zhejiang Province

The First Affiliated Hospital of Wenzhou Medical University

Zhejiang Cancer Hospital

Fakultni nemocnice Kralovske Vinohrady

Nemocnice AGEL Novy Jicin a.s.

Fakultní nemocnice Brno Bohunice

Masarykuv onkologicky ustav

Fakultni Thomayerova nemocnice

Herlev and Gentofte Hospital

Rigshospitalet