NCT06760637|RecruitingPhase 3DMCFDA Drug

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

FourLight-3

AN INTERVENTIONAL, OPEN-LABEL, RANDOMIZED, MULTICENTER PHASE 3 STUDY OF PF-07220060 PLUS LETROZOLE COMPARED TO CDK4/6 INHIBITOR PLUS LETROZOLE IN PARTICIPANTS OVER 18 YEARS OF AGE WITH HORMONE RECEPTOR (HR)-POSITIVE, HER2-NEGATIVE ADVANCED/METASTATIC BREAST CANCER WHO HAVE NOT RECEIVED ANY PRIOR SYSTEMIC ANTICANCER TREATMENT FOR ADVANCED/METASTATIC DISEASE (FOURLIGHT-3)

Pfizer ClinicalTrials.gov

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2 other identifiers

C43910242024-512925-95-00

Study Type

interventional

Target

1,020

Locations

30 countries

Sites

518

Timeline

RegisteredJan 2025

StartedJan 2025

CompletionDec 2037

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

1,020

participants targeted

Target at P75+ for phase_3 breast-cancer

Timeline

142mo left

Started Jan 2025

Longer than P75 for phase_3 breast-cancer

Geographic Reach

30 countries

518 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

13 years study duration

Study Progress10%

Jan 2025Dec 2037

First Submitted

Initial submission to the registry

December 11, 2024

Completed

26 days until next milestone

Study Start

First participant enrolled

January 6, 2025

Completed

1 day until next milestone

First Posted

Study publicly available on registry

January 7, 2025

Completed

4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 2, 2029

Expected

9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 29, 2037

Last Updated

March 2, 2026

Status Verified

February 1, 2026

Enrollment Period

4 years

First QC Date

December 11, 2024

Last Update Submit

February 26, 2026

Conditions

Breast Cancer

Keywords

Locally advanced or metastatic breast cancerEstrogen receptor positive [ER(+)]Progesterone receptor positive [PR(+)]Hormone receptor positive [HR(+)]Human epidermal growth factor receptor 2 negative [HER2(-)]ER(+)/HER2(-)PR(+)/HER2(-)HR(+)/HER2(-)Advanced Breast CancerBreast tumorBreast cancerPalbociclibAbemaciclibRibociclibPartial Response+ (PR+)Metastatic breast cancerHormone TherapyHormone positive breast cancerRecurrent breast cancerHR+HER2-negativeRelapseRecurrentFirst line treatmentLeft Sided Breast CancerLeft-Sided Breast CancerRight Sided Breast CancerRight-Sided Breast CancerUnilateral Breast CancerCancer of the breastCDK4iCDK4/6iBilateral Breast Cancer

Outcome Measures

Primary Outcomes (1)

Progression Free Survival (PFS) by BICR
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
From the date of randomization until disease progression or death due to any cause (up to approximately 4 years)

Secondary Outcomes (11)

Overall Survival (OS)
From the date of randomization until death due to any cause (up to approximately 13 years).
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)
OR by BICR and by investigator
From randomization to progression or death whichever occurs first (up to approximately 4 years)
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)
Incidence of treatment emergent treatment related adverse events (AE)
Duration of the study approximately up to 13 years.
+6 more secondary outcomes

Study Arms (2)

Arm A

EXPERIMENTAL

PF-07220060 tablet taken by mouth plus Letrozole tablet taken by mouth

Drug: PF-07220060Drug: letrozole

Arm B

ACTIVE COMPARATOR

Investigator's Choice of CDK4/6 inhibitor (tablet/capsule) taken by mouth with letrozole tablet taken by mouth

Drug: letrozoleDrug: abemaciclibDrug: palbociclibDrug: ribociclib

Interventions

PF-07220060DRUG

CDK4 inhibitor

Arm A

letrozoleDRUG

endocrine therapy

Arm AArm B

abemaciclibDRUG

CDK4/6 inhibitor

Arm B

palbociclibDRUG

CDK4/6 inhibitor

Arm B

ribociclibDRUG

CDK4/6 inhibitor

Arm B

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Pfizerlead

Study Sites (518)

The Kirklin Clinic of UAB Hospital

Birmingham, Alabama, 35233, United States

RECRUITING

The University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

RECRUITING

University of Alabama at Birmingham Hospital

Birmingham, Alabama, 35249, United States

RECRUITING