A Phase 1/2 interventional study of ARV-471 and Ribociclib in Breast Cancer, sponsored by Pfizer. Active, not recruiting at 29 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-09.
Sponsored by Pfizer · Phase 1/2, Interventional, and Treatment
The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called ARV-471) when given together with other medicines for the potential treatment of advanced or metastatic breast cancer.
This study is seeking participants who have breast cancer that:
This study is divided into separate sub-studies.
For Sub-Study B:
All participants will receive ARV-471 and a medicine called ribociclib. ARV-471 and ribociclib will be given at the same time by mouth, at home, 1 time a day.
The experiences of people receiving the study medicine will be examined. This will help determine if the study medicine is safe and effective.
Participants will continue to take ARV-471 and ribociclib 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.
C4891023 is a prospective, open-label, multicenter, Phase 1b/2 sub-study to evaluate the safety, antitumor activity, and PK of ARV-471 with ribociclib in the treatment of participants with A/MBC. The sub-study is part of Umbrella platform, TACTIVE-U, comprising multiple sub-studies that independently evaluate ARV-471 in participants with with Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Advanced or Metastatic Breast Cancer. ARV-471 will act as the backbone therapy given in combination with other anticancer agents thought to have clinical relevance in ER+ breast cancer.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 20 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.
Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
ARV-471 administered orally QD continuously and Ribociclib administered orally QD consecutively for 21 days followed by 7 days off treatment on 28-day cycles
Drug: ARV-471 · Drug: Ribociclib
Daily oral dosages of ARV-471 continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days
Daily oral dosages of ribociclib consecutively for 21 days followed by 7 days off treatment, cycles lasting 28 days
Phase 1b: Number of Participants With Dose Limiting Toxicities
Dose Limiting Toxicities rate for ARV-471 in combination with Ribociclib, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1 \[28 days\]).
Time frame: Cycle 1 (28 days)
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.
Time frame: Up to approximately 1 year
Drug Drug Interaction cohort: Area Under the Curve from Time Zero to end of dosing interval Evaluation of ribociclib with and without co-administration of ARV-471
Exposure (AUCtau) of ribociclib with and without co-administration of ARV-471
Time frame: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43
Drug Drug Interaction cohort: Maximum Plasma Concentration (Cmax) of ribociclib with and without co-administration of ARV-471
Concentration (Cmax) of ribociclib with and without co-administration of ARV-471
Time frame: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43
Phase 1b, Drug Drug Interaction cohort and Phase 2: number of participants experiencing any AE, SAE, Treatment Related SAE
An adverse event (AE) were any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An 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. 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 Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and coded using MedDRA were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe and Grade 4=life-threatening or disabling and grade 5=death.
Time frame: Up to 28 days after last dose of study treatment
Phase 1b, Drug Drug Interaction cohort and Phase 2: 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 chemistry abnormalities by grade as per CTCAE version 5.0 were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe and 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.
Time frame: Up to 28 days after last dose of study treatment
Phase 1b, Drug Drug Interaction cohort and Phase 2: 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, international normalized ratio increased, prothrombin time. Number of participants with hematological and coagulation abnormalities by grade as per CTCAE version 5.0 were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe and 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.
Time frame: Up to 28 days after last dose of study treatment
Drug Drug Interaction cohort: 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).
Time frame: Up to 28 days after last dose of study treatment
Phase 1b: 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.
Time frame: Up to approximately 1 year
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.
Time frame: Up to approximately 1 year
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
Time frame: Up to approximately 1 year
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.
Time frame: Up to approximately 1 year
Phase 1b: Maximum Observed Plasma Concentration (Cmax) of ARV-471 with and without co-administration of ribociclib
Concentration (Cmax) of ARV-471 with and without co-administration of ribociclib
Time frame: Phase 1b: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43
Phase 1b Area Under the Curve from Time Zero to end of dosing interval Evaluation of ARV-471 with and without co-administration of ribociclib
Exposure (AUCtau) of ARV-471 with and without co-administration of ribociclib
Time frame: Phase 1b: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43
Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of ARV-471
Plasma concentration of ARV-471
Time frame: Phase 1b: pre-dose Day 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43 Phase 2: pre and post dose Day 8, 15, 29 and 43; pre - dose Day 57, 113 and 169
Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of ARV-473
Plasma concentration of ARV-473
Time frame: Phase 1b: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43 Phase 2: pre and post dose Day 8, 15, 29 and 43; pre - dose Day 57, 113 and 169
Phase 1b and Phase 2: Phase 1b: Maximum Observed Plasma Concentration (Cmax) of ribociclib
Plasma concentration of ribociclib
Time frame: Phase 1b: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day 15; post dose Day 8, 29 and 43 Phase 2: pre and post dose Day 8, 15, 29 and 43; pre - dose Day 57, 113 and 169
Phase 2: Overall Survival
Overall Survival (OS) is defined as the time from the date of first dose of study interventions to the date of death due to any cause
Time frame: Through study completion, up to approximately 3 year
Phase 2:ctDNA plasma quantitative changes from pre-treatment
To assess changes from baseline levels in plasma ctDNA with treatment and to evaluate potential predictability of their associations with clinical outcomes.
Time frame: At predefined intervals throughout the treatment period, up to cycle 3 (each cycle is 28 days) and end of treatment
Plan to share: Yes — 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.
This study is active, not recruiting, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.
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