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: PF-07220060

Overview

Atirmociclib (PF-07220060) is an investigational, oral, next‑generation cyclin‑dependent kinase 4 (CDK4)–selective inhibitor being developed primarily for hormone receptor–positive, HER2‑negative (HR+/HER2−) advanced/metastatic breast cancer (mBC). Multiple trials are ongoing, including a global randomized study of PF‑07220060 plus fulvestrant versus fulvestrant or everolimus/exemestane after prior CDK4/6 inhibitor therapy (NCT06105632). This study was presented as a phase 3 design at ASCO 2024 (TPS1129), while current sponsor listings describe it as phase 2; as of August–September 2025 the trial is active but not recruiting. (ascopubs.org)

Mechanism of action

Atirmociclib is a highly selective inhibitor of CDK4 that spares CDK6, aiming to inhibit the cyclin D–CDK4/RB/E2F axis and arrest G1‑S cell‑cycle progression. Preclinical work reports markedly greater selectivity for CDK4 over CDK6 compared with first‑generation CDK4/6 inhibitors (approximately 20‑fold vs palbociclib and ~4‑fold vs abemaciclib/ribociclib). (pfizeroncologydevelopment.com)

Efficacy

Phase 1/2a (first‑in‑human) PF‑07220060 + endocrine therapy (letrozole or fulvestrant) after prior CDK4/6 inhibitor:
At ASCO 2023 (data cutoff Nov 1, 2022), among 26 patients with HR+/HER2− mBC (21 with measurable disease), confirmed objective responses were seen in 6/21 (29%; 1 CR, 5 PR). Clinical benefit rate (CBR: CR+PR+≥24‑week SD) was 52%, and median PFS was 24.7 weeks; 31% remained on treatment ≥60 weeks. (ascopubs.org)
An ESMO Breast Cancer 2024 mini‑oral (Abstract 184MO; updated dataset to Nov 1, 2023) reported 1 CR and 7 PR in 25 patients with measurable disease (CBR 64%) and median PFS 8.1 months. (dailyreporter.esmo.org)
Combination strategy with a selective CDK2 inhibitor (PF‑07104091) to overcome resistance:
Early phase Ib/II dose‑escalation data in heavily pretreated HR+/HER2− mBC showed an ORR of 27.8%, disease control rate 55.6%, and median PFS 8.3 months; neutropenia was the most common grade ≥3 AE. Dose‑expansion is ongoing (NCT05262400). Preclinical ESMO 2024 work supported the biological rationale for CDK4+CDK2 blockade. (mdanderson.org)

No randomized efficacy results in humans have been reported as of October 2025. The international randomized study (NCT06105632; TPS1129) is ongoing. (ascopubs.org)

Safety

In the ASCO 2023 first‑in‑human study (post‑CDK4/6i HR+/HER2− mBC), the most frequent treatment‑emergent AEs with PF‑07220060 + endocrine therapy were diarrhea (50%; 0% grade 3), neutropenia (50%; 15% grade 3), and nausea (39%; 4% grade 3). Dose‑limiting toxicities included grade 3 thrombocytopenia at 500 mg BID monotherapy and grade 3 leukopenia/neutropenia at 400 mg BID + fulvestrant; 300 mg BID was selected for expansion. (ascopubs.org)
ASCO 2024 update (Parts 1B–1C post‑CDK4/6i; Parts 2B–2C CDK4/6i‑naïve): the most common AEs included neutropenia (pooled 1B–1C: 54.5% [18.2% grade 3]; Part 2B: 61.8% [23.5% grade 3]; Part 2C: 36.1% [11.1% grade 3]), leukopenia, and anemia. No grade >3 TEAEs were reported in these cohorts; discontinuations due to AEs occurred in 3.0%–8.3%, and relative dose intensity was ~98%–100%, supporting continuous dosing. (ascopubs.org)
In the early CDK4+CDK2 combination trial, neutropenia was the most common grade ≥3 AE; overall safety was characterized as manageable. (mdanderson.org)

Ongoing trials (selected)

NCT04557449 (Phase 1/2a): PF‑07220060 as monotherapy and with endocrine therapy in advanced solid tumors, enriched for HR+/HER2− mBC. Ongoing dose‑expansion. (pfizeroncologydevelopment.com)
NCT06105632 (FOURLIGHT‑1): randomized PF‑07220060 + fulvestrant versus fulvestrant or everolimus/exemestane after prior CDK4/6 inhibitor; sponsor site currently lists Phase 2; originally presented as Phase 3 (TPS1129). (pfizeroncologydevelopment.com)
NCT05262400 (Phase 1b/2): PF‑07220060 + PF‑07104091 (CDK2 inhibitor) ± endocrine therapy in HR+/HER2− mBC and other tumors. (pfizeroncologydevelopment.com)

HealthScout AI Analysis

Goal: To compare the efficacy and safety of the CDK4-selective inhibitor PF-07220060 plus letrozole versus an approved CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) plus letrozole as first-line therapy for HR-positive, HER2-negative locally advanced or metastatic breast cancer.

Patients: Adults with histologically confirmed HR-positive (ER and/or PR), HER2-negative, locally advanced or metastatic breast cancer not amenable to curative surgery/radiation, with measurable disease or non-measurable bone-only disease per RECIST 1.1, and no prior systemic therapy for advanced/metastatic disease. Key exclusions include visceral crisis, any history of CNS metastases, recurrence within 12 months of prior (neo)adjuvant endocrine therapy or CDK4/6 inhibitor, and significant renal, hepatic, or hematologic dysfunction.

Design: International, multicenter, open-label, randomized phase 3 trial. Approximately 1:1 allocation to investigational combination vs investigator’s choice control, with blinded independent central review for primary PFS endpoint. Planned enrollment is 1020 participants.

Treatments: Arm A: PF-07220060 plus letrozole. PF-07220060 (atirmociclib) is an oral, CDK4-selective inhibitor designed to spare CDK6, aiming to reduce hematologic toxicity relative to dual CDK4/6 inhibition and potentially allow higher target coverage. In a phase 1/2a study in HR+/HER2- metastatic breast cancer post-CDK4/6 inhibitor, PF-07220060 (300–400 mg BID) with endocrine therapy demonstrated an objective response rate of about 32% in measurable disease and a median PFS of 8.1 months, with predominantly low-grade gastrointestinal events and reduced high-grade neutropenia versus historical dual CDK4/6 inhibitor profiles. Arm B: Investigator’s choice of approved CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) plus letrozole, which is a current first-line standard of care for HR+/HER2- metastatic breast cancer.

Outcomes: Primary: Progression-free survival by blinded independent central review per RECIST 1.1. Secondary: Overall survival; investigator-assessed PFS; objective response rate and duration of response by BICR and investigator; safety and tolerability (TEAEs and serious AEs per CTCAE v5.0); patient-reported outcomes including EORTC QLQ-C30, EORTC BR42, BPI-SF, and EQ-5D-5L; and changes in circulating tumor DNA.

Burden on patient: Moderate. Treatments are oral and align with standard first-line endocrine plus CDK inhibition, limiting clinic time. Disease assessments are scheduled approximately every 8 weeks during the first 48 weeks then every 12 weeks, similar to routine care. Safety labs and visits will be regular due to myelosuppression risk and monitoring requirements typical for CDK inhibitors, but no intensive pharmacokinetic schedules or mandatory invasive procedures are indicated. Patient-reported outcome questionnaires and periodic ctDNA sampling add minor additional burden. Overall, the visit and testing frequency are consistent with standard practice for metastatic HR+/HER2- breast cancer receiving CDK inhibitor plus aromatase inhibitor.

Last updated: Oct 2025

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Status: Not yet recruiting

Trial Details

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: PF-07220060

Overview

Mechanism of action

Efficacy

Safety

Ongoing trials (selected)

Further reading

HealthScout AI Analysis

Eligibility

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Sites (452)

Princess Alexandra Hospital

Townsville University Hospital

Frankston Hospital

Peter MacCallum Cancer Centre

Rosebud Hospital

Royal Melbourne Hospital

AZORG Campus Aalst-Moorselbaan

Antwerp University Hospital

Grand Hôpital de Charleroi

AZ Maria Middelares

UZ Leuven

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

Cross Cancer Institute

Dr. Everett Chalmers Regional Hospital

Princess Margaret Cancer Centre

Sunnybrook Research Institute

Anhui Provincial Cancer Hospital

Beijing Cancer hospital

Cancer Hospital Chinese Academy of Medical Science

Peking University People's Hospital

Sun Yat-sen University Cancer Center

The First People's Hospital of Foshan

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

Fakultni nemocnice Kralovske Vinohrady

Nemocnice AGEL Novy Jicin a.s.

Masarykuv onkologicky ustav

Fakultni Thomayerova nemocnice

Fakultni nemocnice v Motole

Fakultni nemocnice Bulovka

Herlev and Gentofte Hospital

Rigshospitalet

Aarhus Universitetshospital, Skejby

Aalborg Universitetshospital, Syd

Næstved Sygehus

Esbjerg sygehus, Syddansk Universitetshospital

Odense Universitetshospital

Sygehus Soenderjylland

Satakunnan Keskussairaala

Tampereen yliopistollinen sairaala

Vaasan Keskussairaala

Turku University Hospital

Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus)

Centre Hospitalier de la Côte Basque

Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest

Centre Eugène Marquis Rennes - Centre de Lutte Contre le Cancer

Centre de Cancérologie du Grand Montpellier

Institut de Cancérologie de l'Ouest