A Study to Learn About the Study Medicine Called PF-07220060 in Combination With Fulvestrant in People With HR-positive, HER2-negative Advanced or Metastatic Breast Cancer Who Progressed After a Prior Line of Treatment

• ClinicalTrials.gov Identifier: NCT06105632
• Recruitment Status: Recruiting
• First Posted: October 27, 2023
• Last Update Posted: April 3, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: October 24, 2023
• First Posted Date: October 27, 2023
• Last Update Posted Date: April 3, 2024
• Actual Study Start Date: January 9, 2024
• Estimated Primary Completion Date: December 16, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 11, 2024): Progression-Free Survival (PFS) progression, as determined by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: From Initiation up to 2 years ]

Original Primary Outcome Measures (submitted: October 24, 2023)

• Progression-Free Survival (PFS) progression, as determined by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: From Initiation up to 2 years ]
• Number of Participants with Objective Response (OR) [ Time Frame: Baseline up to 12 months ]
  same time frame as PFS

Current Secondary Outcome Measures (submitted: March 11, 2024)

• Overall Survival (OS) [ Time Frame: Time from the date of randomization to the date of death due to any cause up to approximately 5 years ]
• PFS as defined by investigator [ Time Frame: Time from the date of randomization up to approximately 2 years ]
• OR by BICR and by investigator per RECIST v1.1 [ Time Frame: 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 (up to approximately 2 years) ]
• Duration of Response (DOR) as define by Blinded Independent Central Review (BICR) and by investigator per RECIST v1.1 [ Time Frame: From the date of the first objective response (every 8 weeks during the first 48 weeks and then every 12 week) up to approximately 2 years. ]
• Number of Participants With Clinical Benefit Response (CBR) by BICR and by investigator per RECIST v1.1 [ Time Frame: From randomization date (every 8 weeks during the first 48 weeks and then every 12 weeks) up to approximately 2 years ]
• Number or Patients with Adverse Events (AEs) by Type [ Time Frame: From screening until 28 days after the last dose, to approximately 3 years ]
• Number or Patients with AEs by Incidence [ Time Frame: From screening until 28 days after the last dose, to approximately 3 years ]
• Number or Patients with AEs by Seriousness [ Time Frame: From screening until 28 days after the last dose, to approximately 3 years ]
• Number or Patients with AEs by relationship to study interventions [ Time Frame: From screening until 28 days after the last dose, to approximately 3 years ]
• Number of Participants With Abnormal Electrocardiogram (ECG) [ Time Frame: From baseline to approximately 2 years ]
• Number of Participants With Laboratory Test Abnormalities [ Time Frame: From screening until 28 days after the last dose to approximately 2 years ]
• EQ-5D-5L [ Time Frame: Screening Days 1, 15 of Cycle 1 and 2, Day 1 of Cycles 3-6, then Day 1 of every other subsequent Cycle starting with Cycle 8 (eg, Cycles 8, 10, 12, etc), EoT and Safety FU until 28 days after the last dose to approximately 2 years. Each Cycle is 28 days ]
• EORTC QLQ [ Time Frame: Screening Days 1, 15 of Cycle 1 and 2, Day 1 of Cycles 3-6, then Day 1 of every other subsequent Cycle starting with Cycle 8 (eg, Cycles 8, 10, 12, etc), EoT and Safety FU until 28 days after the last dose to approximately 2 years. Each Cycle is 28 days ]
• EORTC QLQ Breast Cancer Module 23 (BR23) [ Time Frame: Screening Days 1, 15 of Cycle 1 and 2, Day 1 of Cycles 3-6, then Day 1 of every other subsequent Cycle starting with Cycle 8 (eg, Cycles 8, 10, 12, etc), EoT and Safety FU until 28 days after the last dose to approximately 2 years. Each Cycle is 28 days ]
• Ctrough of PF-07220060 [ Time Frame: Cycle 1 (Day 15), Cycle 2 (Day 1), and Cycle 3 (Day 1). Each Cycle is 28 days ]

Original Secondary Outcome Measures (submitted: October 24, 2023)

• Overall Survival (OS) [ Time Frame: Time from the date of randomization to the date of death due to any cause up to approximately 3 years ]
• PFS as defined by investigator [ Time Frame: Time from the date of randomization up to approximately 2 years ]
• OR as define by investigator [ Time Frame: From Baseline or randomization up to 12 months ]
• Duration of Response (DOR) as define by Blinded Independent Central Review (BICR) and by investigator [ Time Frame: From the date of the first objective response (every 8 weeks during the first 48 weeks and then every 12 week) up to approximately 2 years. ]
• Number of Participants With Clinical Benefit Response (CBR) by BICR and by investigator [ Time Frame: From randomization date (every 8 weeks during the first 48 weeks and then every 12 weeks) up to approximately 2 years ]
• Number or Patients with Adverse Events (AEs) by Type [ Time Frame: From screening until 28 days after the last dose, to approximately 3 years ]
• Number or Patients with AEs by Incidence [ Time Frame: From screening until 28 days after the last dose, to approximately 3 years ]
• Number or Patients with AEs by Seriousness [ Time Frame: From screening until 28 days after the last dose, to approximately 3 years ]
• Number or Patients with AEs by relationship to study interventions [ Time Frame: From screening until 28 days after the last dose, to approximately 3 years ]
• Number of Participants With Abnormal Electrocardiogram (ECG) [ Time Frame: From baseline to approximately 2 years ]
• Number of Participants With Laboratory Test Abnormalities [ Time Frame: From screening until 28 days after the last dose to approximately 2 years ]
• EQ-5D-5L [ Time Frame: Screening Days 1, 15 of Cycle 1 and 2, Day 1 of Cycles 3-6, then Day 1 of every other subsequent Cycle starting with Cycle 8 (eg, Cycles 8, 10, 12, etc), EoT and Safety FU until 28 days after the last dose to approximately 2 years. Each Cycle is 28 days ]
• EORTC QLQ [ Time Frame: Screening Days 1, 15 of Cycle 1 and 2, Day 1 of Cycles 3-6, then Day 1 of every other subsequent Cycle starting with Cycle 8 (eg, Cycles 8, 10, 12, etc), EoT and Safety FU until 28 days after the last dose to approximately 2 years. Each Cycle is 28 days ]
• EORTC QLQ Breast Cancer Module 23 (BR23) [ Time Frame: Screening Days 1, 15 of Cycle 1 and 2, Day 1 of Cycles 3-6, then Day 1 of every other subsequent Cycle starting with Cycle 8 (eg, Cycles 8, 10, 12, etc), EoT and Safety FU until 28 days after the last dose to approximately 2 years. Each Cycle is 28 days ]
• Ctrough of PF-07220060 [ Time Frame: Cycle 1 (Day 15), Cycle 2 (Day 1), and Cycle 3 (Day 1). Each Cycle is 28 days ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Learn About the Study Medicine Called PF-07220060 in Combination With Fulvestrant in People With HR-positive, HER2-negative Advanced or Metastatic Breast Cancer Who Progressed After a Prior Line of Treatment
• Official Title: AN INTERVENTIONAL, OPEN-LABEL, RANDOMIZED, MULTICENTER PHASE 3 STUDY OF PF-07220060 PLUS FULVESTRANT COMPARED TO INVESTIGATOR'S CHOICE OF THERAPY IN PARTICIPANTS OVER 18 YEARS OF AGE WITH HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE ADVANCED/METASTATIC BREAST CANCER WHOSE DISEASE PROGRESSED AFTER PRIOR CDK 4/6 INHIBITOR-BASED THERAPY

Brief Summary

The purpose of this study is to learn about the safety and how effective the study medicine (PF-07220060) plus fulvestrant is compared to the study doctor's choice of treatment in people with advanced or metastatic breast cancer. Advanced cancer is the one that is unlikely to be cured or taken care of with treatment. Metastatic cancer is the one that has spread to other parts of the body.

This study is seeking female and male participants who:

• are 18 years of age or older;
• are hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative;
• have advanced or metastatic breast cancer after taking other treatments before this study;
• have not taken or need to take medications that are not allowed by the study protocol;
• do not have any medical or mental conditions that may increase the risk of study participation.

Half of the participants will take PF-07220060 two times daily by mouth along with fulvestrant. Fulvestrant will be given as a shot into the muscle. The other half will take the study doctor's choice of treatment which can either be:

• Fulvestrant alone taken as shot into the muscle.
• Everolimus along with exemestane taken once daily by mouth.

This study will compare the experiences of participants receiving the study medicine plus fulvestrant to those who are receiving the study doctor's choice of treatment. This will help decide if the study medicine is safe and effective.

Participants will receive study treatment and/or will be in the study until:

• imaging scans (such as an MRI and/or CT) show that their cancer is getting worse.
• the study doctor thinks the participant is no longer benefitting from the study medicine.
• has side effects that become too severe. A side effect is a reaction (expected or unexpected) to a medicine or treatment you take.
• the participant chooses to stop taking part.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced or Metastatic Breast Cancer

Intervention

• Drug: PF-07220060 CDK4 inhibitor
  Experimental
• Drug: Fulvestrant
  Experimental and Active comparator
• Drug: Everolimus
  Active Comparator
• Drug: Exemestane
  Active Comparator

Study Arms

• Experimental: Arm A
  PF-07220060 to be taken by mouth as a tablet in combination with fulvestrant (a solution for injection)
  Interventions:

  • Drug: PF-07220060 CDK4 inhibitor
  • Drug: Fulvestrant
• Active Comparator: Arm B

  Investigator's choice of therapy of either:

  • Fulvestrant alone (a solution for injection), or
  • Everolimus in combination with exemestane, both a tablet to be taken by mouth.
  Interventions:

  • Drug: Fulvestrant
  • Drug: Everolimus
  • Drug: Exemestane

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 24, 2023): 510
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 14, 2028
• Estimated Primary Completion Date: December 16, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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
• Able to provide a sufficient amount of representative formalin fixed, paraffin embedded (FFPE) tumor tissue specimen.
• Must have received CDK4/6i plus NSAI defined per study protocol. There must be documented PD during or after CDK4/6i treatment.
• Measurable disease or non-measurable bone only disease as defined by RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤2.

Exclusion Criteria:

• Any medical or psychiatric condition that may increase the risk of study participation or make the participant inappropriate for the study.
• In visceral crisis at risk of immediately life-threatening complications in the short term.
• Known active uncontrolled or symptomatic central nervous system metastases, carcinomatous meningitis, or leptomeningeal disease.
• Prior treatment with any of the following:
• Everolimus or investigational anti-cancer agents in any setting
• Prior chemotherapy in the advanced setting
• Radiation within 2 weeks of randomization
• Current use or anticipated need for any prohibited food, supplements or concomitant medication(s) (ie, other anti-cancer therapies, other endocrine therapies, growth factors, chronic systemic corticosteroids, strong cytochrome P450 3A4/5 [CYP3A4/5] or uridine 5' diphosphate-glucuronosyltransferase 2B7 [UGT2B7] inhibitors and inducers, direct oral anticoagulants, proton pump inhibitors).
• Inadequate renal function, hepatic dysfunction, or hematologic abnormalities.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Pfizer CT.gov Call Center; 1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

• Listed Location Countries: Argentina, Australia, Brazil, Canada, Israel, Japan, Korea, Republic of, Taiwan, United States

Administrative Information

• NCT Number: NCT06105632
• Other Study ID Numbers: C4391022; 2023-506487-13-00 ( Registry Identifier: CTIS (EU) )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: April 2024