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NCT Number: NCT06760637

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Disease Attributes Neoplasms Neoplasms by Site Pathologic Processes Pathological Conditions, Signs and Symptoms Recurrence Skin Diseases Skin and Connective Tissue Diseases Unilateral Breast Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Organizacion Medica de Investigacion, CABA, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

PF-07220060

Drug

CDK4 inhibitor

letrozole

Drug

endocrine therapy

Abemaciclib

Drug

CDK4/6 inhibitor

Palbociclib

Drug

CDK4/6 inhibitor

Ribociclib

Drug

CDK4/6 inhibitor

Primary outcomes

  1. Progression Free Survival (PFS) by BICR

    Time frame: 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 outcomes

  1. Overall Survival (OS)

    Time frame: 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

  2. Progression Free Survival (PFS) by Investigator

    Time frame: 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

  3. OR by BICR and by investigator

    Time frame: 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

  4. Duration of Response (DoR) by BICR and by investigator

    Time frame: 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

  5. Incidence of treatment emergent treatment related adverse events (AE)

    Time frame: Duration of the study approximately up to 13 years.

    Incidence and severity of AEs graded according to the NCI CTCAE v5.0

  6. Incidence of treatment emergent treatment related serious adverse events

    Time frame: Duration of the study approximately up to 13 years.

    Incidence and severity of AEs graded according to NCI CTCAE v5.0

  7. Estimated mean change from baseline in EORTC QLQ C30

    Time frame: Baseline to end of treatment (up to approximately 4 years)

  8. Estimated mean change from baseline in BPI-SF

    Time frame: Baseline to end of treatment (up to approximately 4 years)

  9. Estimated mean change from baseline in EQ-5D-5L

    Time frame: Baseline to end of treatment (up to approximately 4 years)

  10. Estimated mean change from baseline in EORTC Breast Cancer Module (BR42)

    Time frame: Baseline to end of treatment (up to approximately 4 years)

  11. Mean change from baseline of ctDNA

    Time frame: Baseline to end of treatment (up to approximately 4 years)

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study title

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)

Acronym: FourLight-3

Important dates

Study start
2025
Primary completion
2029
Study completion
2037
First posted
Jan 7, 2025
Registry last updated
May 19, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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