Breast CancerPhase 1/2NCT05573555
TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study B)
A Phase 1/2 study testing ARV-471 and Ribociclib in people with Breast Cancer, run by Pfizer at 29 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- ARV-471 and Ribociclib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 29 sitesin 4 countries
- Study dates
- 1 Mar 2023to 30 Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- histological or cytological diagnosis of ER+ and HER2- advanced/metastatic breast cancer that is not amendable to surgical resection with curative intent (≥1% ER+ stained cells on the most recent tumor biopsy).
- prior anticancer therapies: at least 1 and no more than 2 lines of prior therapies for advanced/metastatic disease; 1, and only 1, line of any CDK4/6 inhibitor-based regimen is required (in any setting eg adjuvant, metastatic)
- at least 1 measurable lesion as defined by RECIST v1.1.
- ECOG PS ≤1.
Who cannot join
- visceral crisis at risk of life-threatening complications in the short term
- known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung functions.
- newly diagnosed brain metastases, or symptomatic 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 14 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
- impaired cardiovascular function or clinically significant cardiovascular diseases
Show all 9Show fewer
- concurrent administration of medications, food, or herb supplements that are strong inhibitors and strong/moderate inducers of CYP3A 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
Trial locations and contacts
29 sites in 4 countries.
29 sites in 4 countries
United States20 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Siteman Cancer Center - St Peters
City of Saint Peters, Missouri, 63376
Siteman Cancer Center - West County
Creve Coeur, Missouri, 63141
Siteman Cancer Center - North County
Florissant, Missouri, 63031
Dana-Farber Cancer Institute - Chestnut Hill
Newton, Massachusetts, 02459
Stanford Women's Cancer Center
Palo Alto, California, 94304
UCSF Medical Center at Mission Bay
San Francisco, California, 94158
Siteman Cancer Center - WUPI
Shiloh, Illinois, 62269
Siteman Cancer Center
St Louis, Missouri, 63108
Barnes Jewish Hospital Department of Laboratories
St Louis, Missouri, 63110
Barnes-Jewish Hospital
St Louis, Missouri, 63110
Washington University School of Medicine - Siteman Cancer Center
St Louis, Missouri, 63110
Washington University School of Medicine
St Louis, Missouri, 63110
Barnes Jewish Hospital Lab- South County
St Louis, Missouri, 63129
Siteman Cancer Center - South County
St Louis, Missouri, 63129
Moffitt Cancer Center - International Plaza
Tampa, Florida, 33607
Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center
Tampa, Florida, 33612
Moffitt Cancer Center
Tampa, Florida, 33612
Moffitt McKinley Hospital
Tampa, Florida, 33612
Canada6 sites
CIUSSS- saguenay-Lac-Saint-Jean
Chicoutimi, Quebec, G7H 5H6
Jewish General Hospital
Montreal, Quebec, H3T 1E2
The Ottawa Hospital - General Campus
Ottawa, Ontario, K1H 8L6
Sunnybrook Research Institute
Toronto, Ontario, M4N 3M5
BC Cancer Vancouver
Vancouver, British Columbia, V5Z 1H7
BC Cancer Vancouver
Vancouver, British Columbia, V5Z 4E6
Spain2 sites
Hospital Universitario 12 de Octubre
Madrid, Madrid, Comunidad de, 28041
Hospital Universitario Virgen Del Rocio
Seville, 41013
About this study
Official title: TACTIVE-U: AN INTERVENTIONAL SAFETY AND EFFICACY PHASE 1B/2, OPEN-LABEL UMBRELLA STUDY TO INVESTIGATE TOLERABILITY, PK, AND ANTITUMOR ACTIVITY OF VEPDEGESTRANT (ARV-471/PF-07850327), AN ORAL PROTEOLYSIS TARGETING CHIMERA, IN COMBINATION WITH OTHER ANTICANCER TREATMENTS IN PARTICIPANTS AGED 18 YEARS AND OVER WITH ER+ ADVANCED OR METASTATIC BREAST CANCER, SUB-STUDY B (ARV-471 IN COMBINATION WITH RIBOCICLIB)
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:
Read more
- is advanced, may have spread to other organs (metastatic) and cannot be fully treated by surgery or radiation therapy
- is sensitive to hormonal therapy (it is called estrogen receptor positive); and
- is no longer responding to previous treatments
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.
Read the detailed description
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.
- Conditions
- Breast Cancer
- Being tested
- ARV-471, Ribociclib
- Keywords
- TACTIVE-U; Umbrella study; PROTAC; metastatic breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARV-471Drug
Daily oral dosages of ARV-471 continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days
RibociclibDrug
Daily oral dosages of ribociclib consecutively for 21 days followed by 7 days off treatment, cycles lasting 28 days
| Study group | Role | What they receive |
|---|---|---|
| ARV-471 in combination with Ribociclib | Experimental | 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 Receives: Drug: ARV-471; Drug: Ribociclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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]).
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Secondary outcomes (15)
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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: At predefined intervals throughout the treatment period, up to cycle 3 (each cycle is 28 days) and end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2022
- Study start1 Mar 2023
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Phase 1b will use an escalation/de-escalation approach to determine the RP2D of ARV-471 when administered in combination with ribociclib. The decision to escalate the starting dose level of ARV-471 will be using mTPI-2 decision criteria based on the number of DLT-evaluable participants and the number of DLTs in those participants during the DLT observation period (Cycle 1). During Phase 1b, a 7 days lead-in period will be conducted with ARV-471 as monotherapy. Phase 2 will further evaluate the preliminary antitumor activity and safety of the combination RP2D. In addition, the potential drug-drug interaction (DDI) between ARV-471 and ribociclib will be evaluated, at the doses selected for the ph2 portion, in a DDI Assessment Cohort(s)
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Arvinas Estrogen Receptor, Inc.
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05573555
- Sponsor's protocol ID
- C4891023
- Other IDs
- 2022-502231-19-00
- Status last verified
- Mar 2026
- First submitted
- 5 Oct 2022
- Last updated
- 9 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TACTIVE-U: AN INTERVENTIONAL SAFETY AND EFFICACY PHASE 1B/2, OPEN-LABEL UMBRELLA STUDY TO INVESTIGATE TOLERABILITY, PK, AND ANTITUMOR ACTIVITY OF VEPDEGESTRANT (ARV-471/PF-07850327), AN ORAL PROTEOLYSIS TARGETING CHIMERA, IN COMBINATION WITH OTHER ANTICANCER TREATMENTS IN PARTICIPANTS AGED 18 YEARS AND OVER WITH ER+ ADVANCED OR METASTATIC BREAST CANCER, SUB-STUDY B (ARV-471 IN COMBINATION WITH RIBOCICLIB)
- ClinicalTrials.gov ID
- NCT05573555
- Acronym / sponsor ID
- C4891023
- Conditions
- Breast Cancer
- Keywords
- TACTIVE-U; Umbrella study; PROTAC; metastatic breast cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Collaborators
- Arvinas Estrogen Receptor, Inc.
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 10 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- is advanced, may have spread to other organs (metastatic) and cannot be fully treated by surgery or radiation therapy
- is sensitive to hormonal therapy (it is called estrogen receptor positive); and
- is no longer responding to previous treatments
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase 1b will use an escalation/de-escalation approach to determine the RP2D of ARV-471 when administered in combination with ribociclib. The decision to escalate the starting dose level of ARV-471 will be using mTPI-2 decision criteria based on the number of DLT-evaluable participants and the number of DLTs in those participants during the DLT observation period (Cycle 1). During Phase 1b, a 7 days lead-in period will be conducted with ARV-471 as monotherapy. Phase 2 will further evaluate the preliminary antitumor activity and safety of the combination RP2D. In addition, the potential drug-drug interaction (DDI) between ARV-471 and ribociclib will be evaluated, at the doses selected for the ph2 portion, in a DDI Assessment Cohort(s)
| Arm | Type | Receives |
|---|---|---|
| ARV-471 in combination with Ribociclib | Experimental | Drug: ARV-471, Drug: RibociclibARV-471 administered orally QD continuously and Ribociclib administered orally QD consecutively for 21 days followed by 7 days off treatment on 28-day cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- histological or cytological diagnosis of ER+ and HER2- advanced/metastatic breast cancer that is not amendable to surgical resection with curative intent (≥1% ER+ stained cells on the most recent tumor biopsy).
- prior anticancer therapies: at least 1 and no more than 2 lines of prior therapies for advanced/metastatic disease; 1, and only 1, line of any CDK4/6 inhibitor-based regimen is required (in any setting eg adjuvant, metastatic)
- at least 1 measurable lesion as defined by RECIST v1.1.
- ECOG PS ≤1.
Key exclusion criteria (9 listed)
- visceral crisis at risk of life-threatening complications in the short term
- known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung functions.
- newly diagnosed brain metastases, or symptomatic 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 14 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARV-471Daily oral dosages of ARV-471 continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days | Drug | ARV-471 in combination with Ribociclib |
| RibociclibDaily oral dosages of ribociclib consecutively for 21 days followed by 7 days off treatment, cycles lasting 28 days | Drug | ARV-471 in combination with Ribociclib |
Primary outcome
Phase 1b: Number of Participants With Dose Limiting Toxicities
Time frame: Cycle 1 (28 days)
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]).
Phase 2: Percentage of Participants With Objective Response by investigator assessment
Time frame: Up to approximately 1 year
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.
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
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
Exposure (AUCtau) of ribociclib with and without co-administration of ARV-471
Drug Drug Interaction cohort: Maximum Plasma 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
Concentration (Cmax) of ribociclib with and without co-administration of ARV-471
15 secondary outcomes
Phase 1b, Drug Drug Interaction cohort and Phase 2: number of participants experiencing any AE, SAE, Treatment Related SAE
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
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
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
Time frame: Up to 28 days after last dose of study treatment
Phase 1b: Percentage of Participants With Objective Response by investigator assessment
Time frame: Up to approximately 1 year
Phase 1b and Phase 2: Duration of Response by investigator assessment.
Time frame: Up to approximately 1 year
Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment.
Time frame: Up to approximately 1 year
Phase 1b and Phase 2: Progression Free Survival by investigator assessment.
Time frame: Up to approximately 1 year
Phase 1b: Maximum Observed Plasma 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
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
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
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
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
Time frame: Through study completion, up to approximately 3 year
Phase 2:ctDNA plasma quantitative changes from pre-treatment
Time frame: At predefined intervals throughout the treatment period, up to cycle 3 (each cycle is 28 days) and end of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2026.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
29 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ARV-471 and Ribociclib in people with Breast Cancer, run by Pfizer at 29 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 9 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Canada, Spain, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1b: Number of Participants With Dose Limiting Toxicities (time frame: Cycle 1 (28 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2026; AzTrials last refreshed its copy on 27 Oct 2026.