A Study to Learn About Vepdegestrant When Given With PF-07220060 to People With Advanced or Metastatic Breast Cancer.

Breast Cancer Clinical Trial

Official title:

AN INTERVENTIONAL SAFETY AND EFFICACY PHASE 1B/2, OPEN-LABEL STUDY TO INVESTIGATE TOLERABILITY, PK, AND ANTITUMOR ACTIVITY OF VEPDEGESTRANT (ARV-471/PF-07850327), AN ORAL PROTEOLYSIS TARGETING CHIMERA, IN COMBINATION WITH PF-07220060 IN PARTICIPANTS AGED 18 YEARS AND OLDER WITH ER+/HER2- ADVANCED OR METASTATIC BREAST CANCER

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06206837
• Other study ID #: C4891026
• Secondary ID: 2023-508130-33-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 19, 2024
• Est. completion date: February 13, 2026

Study information

• Verified date: May 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to learn about the safety and effects of giving vepdegestrant along with PF-07220060. Vepdegestrant is studied to see if it can be a possible treatment for advanced metastatic breast cancer. This type of cancer would have spread from where it started (breast) to other parts of the body and would be tough to treat. The study is seeking for participants who have breast cancer that: - is hard to treat (advanced) and may have spread to other organs (metastatic). - is sensitive to hormonal therapy (it is called estrogen receptor positive). - is no longer responding to treatments taken before starting this study. All the participants will receive vepdegestrant and PF-07220060. Both medicines will be taken by mouth. The medicines will be taken at home. The experience of people receiving the study medicines will be studied. This will help see if the study medicines are safe and effective. Participants will continue to take vepdegestrant and PF-07220060 until: - their cancer is no longer responding, or - side effects become too severe. They will have visits at the study clinic about every 4 weeks.

Description:

C4891026 is a prospective, open-label, multicenter, Phase 1b/2 study to evaluate the safety, antitumor activity, and pharmacokinetic (PK) of vepdegestrant in combination with PF-07220060 in the treatment of participants with Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Advanced or Metastatic Breast Cancer.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 65
• Est. completion date: February 13, 2026
• Est. primary completion date: August 14, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histological or cytological diagnosis of breast cancer. At time of enrollment this must not be amenable to surgical resection with curative intent (=1% ER+ stained cells as per local practice on the most recent tumor biopsy HER2- tumor by IHC or in-situ hybridization per ASCO/CAP).
• prior anticancer therapies: Phase 1b: at least 1 line of SOC for A/MBC; Prior fulvestrant allowed; =1 prior chemotherapy line (no antibody-drug conjugates permitted) for A/MBC setting allowed. Phase 2: At least one and maximum 2 lines of ET in A/MBC setting and most recent ET-based regimen for >6 months. 1, and only 1, prior CDK4/6 inhibitor-based regimen required. Up to 1 prior regimen of cytotoxic chemotherapy (no antibody-drug conjugates permitted) in the A/MBC setting; Prior fulvestrant allowed.
• Participant with only non-measurable lesion (Phase1b) or at least 1 measurable lesion as defined by RECIST v1.1. (Phase2) are eligible.
• ECOG PS = 0 or 1 (Phase1b) ; =2 (Phase2)

Exclusion Criteria:

• visceral crisis at risk of life-threatening complications in the short term.
• Any condition precluding an adeguate absorption of study interventions.
• newly diagnosed brain metastases, or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated, clinically stable and discontinued anti-seizure medications and corticosteroids for at least 28 days prior to enrollment in the of study.
• history of any other tumor malignancies within the past 3 years, except for the following: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated in situ carcinoma of the cervix. Inflammatory breast cancer are excluded
• impaired cardiovascular function or clinically significant cardiovascular diseases.
• concurrent administration of medications, food, or herb supplements that are strong inhibitors/inducers of CYP3A or UGT2B7, moderate inducers of CYP34 (Phase1b only) and drugs known to predispose to Torsade de Pointes or QT interval prolongation.
• renal impairment, not adequate liver function and/or bone marrow function.
• known active infection

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• vepdegestrant
Daily oral dosages of vepdegestrant continuously, dose escalation/de-escalation in Phase 1b until recommended phase 2 dose (RP2D) determined, cycles lasting 28 days
• PF-07220060
Daily oral dosages of PF-07220060 continuously, dose escalation/de-escalation in Phase 1b until recommended phase 2 dose (RP2D) determined, cycles lasting 28 days

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Puerto Rico	BRCR Global - Mayagüez	Mayaguez
Puerto Rico	Pan American Center for Oncology Trials, LLC	Rio Piedras
United States	UCHealth Harmony	Fort Collins	Colorado
United States	UCHealth Poudre Valley Hospital	Fort Collins	Colorado
United States	START Midwest	Grand Rapids	Michigan
United States	UCHealth Greeley Hospital	Greeley	Colorado
United States	UCHealth - Medical Center of the Rockies	Loveland	Colorado
United States	South Texas Accelerated Research Therapeutics (START)	San Antonio	Texas
United States	START Mountain Region	West Valley City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Arvinas Estrogen Receptor, Inc.

Countries where clinical trial is conducted

United States,  Japan,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b: Number of Participants With Dose Limiting Toxicities	Dose Limiting Toxicities (DLTs) rate for Vepdegestrant in combination with PF-07220060, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1).	28 days
Primary	Phase 2: Percentage of Participants With Objective Response by investigator assessment	Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. as determined by investigator assessment.	Up to approximately 1 year
Secondary	Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants experiencing any AE, SAE, treatment-related AE and treatment-related SAE)	An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A severe adverse event (SAE) is any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. A treatment-related AE is any untoward medical occurrence attributed to study drug in a participant who received study drug.; AEs were graded by the investigator according to the CTCAE version 5.0 and coded using MedDRA were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling; and Grade 5=death.	First study drug dose through a minimum of 28 Days After Last study drug administration
Secondary	Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities - Hematology and coagulation parameters)	Blood samples were collected for the analysis of the following hematology and coagulation parameters: hemoglobin [g/L], platelets, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils [10^9/L]; partial thromboplastin time prolonged and prothrombin time [seconds]; international normalized ratio increased. Number of participants with hematological and coagulation abnormalities by grade as per Common Terminology Criteria for Adverse Events (CTCAE version 5.0) were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling; and Grade 5=death. For laboratory tests without CTCAE grade definitions, results will be categorized as normal, abnormal, or not done.	First study drug dose through a minimum of 28 Days After Last study drug administration
Secondary	Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities - chemistry parameters)	Blood samples were collected for analysis of clinical chemistry parameters. These included: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, [international unit per liter (IU/L)] ; Lipase and amilase [IU/L] (limited to cycle1 only); Albumin, bilirubin, urea ,calcium, creatinine, glucose, magnesium, phosphate, uric acid chloride, potassium and sodium [millimol per liter (mmol/L)]; eGFR [milliliter per minute (ml/min)]. Number of participants with hematological and coagulation abnormalities by grade as per Common Terminology Criteria for Adverse Events (CTCAE version 5.0) were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling; Grade 5=death. For laboratory tests without CTCAE grade definitions, results will be categorized as normal, abnormal, or not done.	First study drug dose through a minimum of 28 Days After Last study drug administration
Secondary	Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants with changes from baseline for ECG parameters)	The following ECG parameters were analyzed and changes from baseline were assessed : heart rate, PR interval, QT interval, QRS interval and QT interval corrected using Fridericia's formula (QTcF).	First study drug dose through a minimum of 28 Days After Last study drug administration
Secondary	Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants experiencing any AE, SAE, treatment-related AE and treatment-related SAE)	"An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A severe adverse event (SAE) is any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. A treatment-related AE is any untoward medical occurrence attributed to study drug in a participant who received study drug.; AEs were graded by the investigator according to the CTCAE version 5.0 and coded using MedDRA where reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling; and Grade 5=death."	First study drug dose through a minimum of 28 Days After Last study drug administration
Secondary	Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities- Hematology and coagulation parameters)	Blood samples were collected for the analysis of following hematology and coagulation parameters: hemoglobin [g/L], platelets, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils [10^9/L]; partial thromboplastin time prolonged and prothrombin time [seconds]; international normalized ratio increased. Number of participants with hematological and coagulation abnormalities by grade as per Common Terminology Criteria for Adverse Events (CTCAE version 5.0) were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling; and Grade 5=death. For laboratory tests without CTCAE grade definitions, results will be categorized as normal, abnormal, or not done.	First study drug dose through a minimum of 28 Days After Last study drug administration
Secondary	Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities - chemistry parameters)	Blood samples were collected for analysis of clinical chemistry parameters. These included: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, [international unit per liter (IU/L)] ; Lipase and amilase [IU/L] (limited to cycle1 only); Albumin, bilirubin, urea ,calcium, creatinine, glucose, magnesium, phosphate, uric acid chloride, potassium and sodium [millimol per liter (mmol/L)]; eGFR [milliliter per minute (ml/min)]. Number of participants with hematological and coagulation abnormalities by grade as per Common Terminology Criteria for Adverse Events (CTCAE version 5.0) were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling; and Grade 5=death. For laboratory tests without CTCAE grade definitions, results will be categorized as normal, abnormal, or not done.	First study drug dose through a minimum of 28 Days After Last study drug administration
Secondary	Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants with changes from baseline for ECG parameters)	Following ECG parameters were analyzed and changes from baseline were assessed: heart rate , PR interval, QT interval, QRS interval and QT interval corrected using Fridericia's formula (QTcF).	First study drug dose through a minimum of 28 Days After Last study drug administration
Secondary	Phase 1b: To evaluate antitumor activity of Vepdegestrant in combination with PF-07220060	Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. as determined by investigator assessment.	Up to approximately 1 year
Secondary	Phase 1b and Phase 2: Duration of Response by investigator assessment.	Duration of Response (DoR) is defined for participants with confirmed OR (CR or PR) as the time from the first documentation of OR to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.	Up to approximately 1 year
Secondary	Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment.	Clinical Benefit Response (CBR) is defined as the proportion of participants with Best Overall Response of confirmed CR or PR at any time, or Stable Disease (SD) =24 weeks	Up to approximately 1 year
Secondary	Phase 1b and Phase 2: Progression Free Survival by investigator assessment.	Progression Free Survival (PFS) is defined as the time from the date of first dose of study interventions to the date of first documentation of PD or death due to any cause, whichever occurs first.	Up to approximately 1 year
Secondary	Phase 1b and Phase 2: Plasma concentrations of Vepdegestrant, ARV-473 and PF-07220060 when given in combination.	To evaluate the plasma exposure of vepdegestrant, ARV-473, and PF-07220060 when vepdegestrant and PF-07220060 are given in combination.	Phase 1b: Pre-dose Day 8; Pre-, 0.5, 1, 2, 4, 6, 8, 12h post-dose Day 15; Pre- and 4-8h post-dose 29; Pre- and 4-8h post-dose Day 43; Pre-dose Days 57, 113 and 169. Phase 2: Pre- and 4-8h post-dose Days 15, 29 and 43; Pre-dose Days 57, 113 and 169
Secondary	Phase 1b: Evaluation of the PK of Vepdegestrant and PF-07220060 when given in combination	Steady-state Cmax (maximum observed serum concentration of drug [Micrograms per milliliter]) of vepdegestrant, ARV-473, and PF-07220060.	Phase 1b (a cycle is 28 days): Pre-dose on Day 8 of Cycle 1; Pre-dose, 0.5, 1, 2, 4, 6, 8, 12h post-dose on Day 15 of Cycle 1; Pre-dose and 4-8h on Day 1 of Cycle 2; Pre-dose and 4-8h post-dose on Day 15 of Cycle 2; Pre-dose on Day 1 of Cycles 3, 5 and 7
Secondary	Phase 1b: Evaluation of the PK of Vepdegestrant and PF-07220060 when given in combination	Steady-state Tmax (time taken (in hours) to reach the maximum serum drug concentration) of vepdegestrant, ARV-473, and PF-07220060.	Phase 1b (a cycle is 28 days): Pre-dose on Day 8 of Cycle 1; Pre-dose, 0.5, 1, 2, 4, 6, 8, 12h post-dose on Day 15 of Cycle 1; Pre-dose and 4-8h on Day 1 of Cycle 2; Pre-dose and 4-8h post-dose on Day 15 of Cycle 2; Pre-dose on Day 1 of Cycles 3, 5 and 7
Secondary	Phase 1b: Evaluation of the PK of Vepdegestrant and PF-07220060 when given in combination	Steady-state AUClast (Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) of vepdegestrant, ARV-473, and PF-07220060.	Phase 1b (a cycle is 28 days): Pre-dose on Day 8 of Cycle 1; Pre-dose, 0.5, 1, 2, 4, 6, 8, 12h post-dose on Day 15 of Cycle 1; Pre-dose and 4-8h on Day 1 of Cycle 2; Pre-dose and 4-8h post-dose on Day 15 of Cycle 2; Pre-dose on Day 1 of Cycles 3, 5 and 7
Secondary	Phase 2:ctDNA plasma quantitative changes from pre-treatment	To assess changes from baseline levels in plasma circulating tumor DNA (ctDNA) with treatment and to evaluate potential predictability of their associations with clinical outcomes.	Phase 2 (each cycle is 28 days): Pre-dose on Day 1 of Cycles 1, 2 and 3 and after last treatment administration.

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