Study of PF-07220060 With Letrozole in Adults With HR-positive HER2-negative Breast Cancer Who Have Not Received Anticancer Treatment for Advanced/Metastatic Disease

Phase 3

Recruiting

• Conditions: Breast Cancer
• Interventions: Drug: PF-07220060; Drug: letrozole; Drug: abemaciclib; Drug: palbociclib; Drug: ribociclib

• Registration Number: NCT06760637
• Lead Sponsor: Pfizer

Brief Summary

The purpose of this study is to determine the safety and efficacy of PF-07220060 with letrozole compared to approved treatments (ie, palbociclib, ribociclib or abemaciclib with letrozole) in people with breast cancer:

* HR-positive (breast cancer cells that need estrogen or progesterone to grow)

* HER2-negative (cells that have a small amount or none of a protein called HER2 on their surface);

* locally advanced (that has spread from where it started to nearby tissue or lymph nodes) or metastatic disease (the spread of cancer to other places in the body)

* who have not received any prior systemic anti-cancer treatment for advanced/metastatic disease.

Approximately half of the participants will receive PF-07220060 plus letrozole while the other half of participants will receive the investigator's choice of treatment plus letrozole.

The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-12-11
• Study First Submitted QC: 2025-01-03
• Study Start: 2025-01-06
• Study First Posted: 2025-01-07
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-17
• Last Update Posted: 2025-06-22
• Primary Completion: 2029-01-02
• Study Completion: 2037-12-29

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1020

Inclusion Criteria

• Histological confirmation of breast cancer with evidence of locally advanced or metastatic disease, which is not amenable to surgical resection or radiation therapy with curative intent.
• Documented estrogen receptor (ER) and/or progesterone receptor (PR)-positive tumor
• Documented HER2-negative tumor
• Previously untreated with any systemic anticancer therapy for their locally advanced or metastatic disease.
• Measurable disease or non-measurable bone only disease as defined by RECIST version 1.1

Exclusion Criteria

• In visceral crisis at risk of immediately life-threatening complications in the short term.
• Current or past history of central nervous system metastases.
• Have received prior (neo)adjuvant endocrine therapy (ET) and had recurrence during or within 12 months after the last dose of ET.
• Have received prior (neo)adjuvant CDK4/6i and had recurrence during or within 12 months after the last dose of CDK4/6i.
• Inadequate renal function, hepatic dysfunction, or hematologic abnormalities.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	letrozole	PF-07220060 tablet taken by mouth plus Letrozole tablet taken by mouth
Arm B	letrozole	Investigator's Choice of CDK4/6 inhibitor (tablet/capsule) taken by mouth with letrozole tablet taken by mouth
Arm B	abemaciclib	Investigator's Choice of CDK4/6 inhibitor (tablet/capsule) taken by mouth with letrozole tablet taken by mouth
Arm B	palbociclib	Investigator's Choice of CDK4/6 inhibitor (tablet/capsule) taken by mouth with letrozole tablet taken by mouth
Arm B	ribociclib	Investigator's Choice of CDK4/6 inhibitor (tablet/capsule) taken by mouth with letrozole tablet taken by mouth
Arm A	PF-07220060	PF-07220060 tablet taken by mouth plus Letrozole tablet taken by mouth

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) by BICR	From the date of randomization until disease progression or death due to any cause (up to approximately 4 years)	Time from the date of randomization to the date of the first documentation of objective progressive disease as determined by blinded independent central review (BICR) per RECIST v1.1, or death due to any cause, whichever occurs first

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From the date of randomization until death due to any cause (up to approximately 13 years).	Time from the date of randomization to the date of death due to any cause
OR by BICR and by investigator	From randomization to progression or death whichever occurs first (up to approximately 4 years)	Time from randomization date (every 8 weeks during the first 48 weeks and then every 12 weeks) to the date of progression OR death whichever occurs first
Progression Free Survival (PFS) by Investigator	From the date of randomization until disease progression or death due to any cause (up to approximately 4 years)	Time from the date of randomization to the date of the first documentation of objective progressive disease as determined by investigator per RECIST v1.1, or death due to any cause, whichever occurs first
Duration of Response (DoR) by BICR and by investigator	From the date of CR or PR until objective progressive disease, or death (up to approximately 4 years)	Time from the date of CR or PR to the first documentation of objective progressive disease, or death due to any cause, whichever occurs first
Incidence of treatment emergent treatment related adverse events (AE)	Duration of the study approximately up to 13 years.	Incidence and severity of AEs graded according to the NCI CTCAE v5.0
Incidence of treatment emergent treatment related serious adverse events	Duration of the study approximately up to 13 years.	Incidence and severity of AEs graded according to NCI CTCAE v5.0
Estimated mean change from baseline in EORTC QLQ C30	Baseline to end of treatment (up to approximately 4 years)
Estimated mean change from baseline in BPI-SF	Baseline to end of treatment (up to approximately 4 years)
Estimated mean change from baseline in EQ-5D-5L	Baseline to end of treatment (up to approximately 4 years)
Estimated mean change from baseline in EORTC Breast Cancer Module (BR42)	Baseline to end of treatment (up to approximately 4 years)
Mean change from baseline of ctDNA	Baseline to end of treatment (up to approximately 4 years)

Trial Locations

Locations (234)

Ironwood Cancer & Research Centers; 🇺🇸 Scottsdale, Arizona, United States

Highlands Oncology; 🇺🇸 Rogers, Arkansas, United States

Highlands Oncology Group; 🇺🇸 Springdale, Arkansas, United States

Cancer and Blood Specialty Clinic / Cancer and Blood Research Center, LLC; 🇺🇸 Los Alamitos, California, United States

Keck Hospital of USC; 🇺🇸 Los Angeles, California, United States

Los Angeles General Medical Center; 🇺🇸 Los Angeles, California, United States

Norris Healthcare Center 3 (HC3); 🇺🇸 Los Angeles, California, United States

USC/Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Keck Medicine of USC Norris Oncology/Hematology - Newport Beach Treatment Center; 🇺🇸 Newport Beach, California, United States

USC Norris Oncology/Hematology - Newport Beach; 🇺🇸 Newport Beach, California, United States

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