TACTIVE-U: A Study to Learn About the Study Medicine (Called ARV-471) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study A)
Study Details
Study Description
Brief 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.
This study is seeking participants who have breast cancer that:
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is advanced, may have spread to other organs (metastatic) and cannot be fully treated by surgery or radiation therapy
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is sensitive to hormonal therapy (it is called estrogen receptor positive); and
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is no longer responding to previous treatments This study is divided into separate sub-studies.
For Sub-Study A:
All participants will receive ARV-471 and a medicine called abemaciclib. ARV-471 will be given by mouth, at home, 1 time a day. Abemaciclib will be given by mouth, at home, 2 times a day. We will examine the experiences of people receiving the study medicines. This will help us determine if the study medicines are safe and effective.
Participants will continue to take ARV-471 and abemaciclib 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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
C4891006 is a sub-study from the Umbrella platform, TACTIVE-U, comprising multiple sub-studies that independently evaluate ARV-471 in participants with Estrogen Receptor Positive (ER+) Advanced or Metastatic Breast Cancer (A/MBC). 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
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: ARV-471 in combination with Abemaciclib ARV-471 administered orally once daily (QD) and Abemaciclib orally twice daily (BID) on 28-day cycle |
Drug: ARV-471
Daily oral dosages of ARV-471 continuously, dose escalation/de-escalation in Phase 1b until the recommended phase 2 dose (RP2D) determined, cycles lasting 28 days
Drug: Abemaciclib
Daily oral dosages of Abemaciclib continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days
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Outcome Measures
Primary Outcome Measures
- Phase 1b: Number of Participants With Dose Limiting Toxicities [28 days]
Dose Limiting Toxicities rate for ARV-471 in combination with Abemaciclib, 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 [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.
Secondary Outcome Measures
- Phase 1b: Percentage of Participants With Objective Response by investigator assessment [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.
- Phase 1b and Phase 2: Evaluation of Safety and Tolerability of ARV-471 in combination with Abemaciclib [First study drug dose through a minimum of 28 Days After Last study drug administration]
AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to ARV-471 in combination with abemaciclib. Laboratory test abnormalities as characterized by type, frequency, intensity (as graded by NCI CTCAE version 5.0), and timing.
- Phase 1b and Phase 2: Duration of Response by investigator assessment. [Up to approximately 1 year]
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.
- Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment. [Up to approximately 1 year]
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
- Phase 1b and Phase 2: Progression Free Survival by investigator assessment. [Up to approximately 1 year]
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.
- Phase 1b and Phase 2: Plasma concentrations of ARV-471 and abemaciclib. [At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)]
- Phase 2: Overall Survival [Through study completion, up to approximately 3 year]
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
- Phase 2:ctDNA plasma quantitative changes from pre-treatment [At predefined intervals throughout the treatment period, an average of 1 year]
Eligibility Criteria
Criteria
Inclusion Criteria:
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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).
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prior anticancer therapies: up to 2 lines of prior therapies for advanced/metastatic disease; only 1 line of any CDK4/6 inhibitor-based regimen is allowed
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at least 1 measurable lesion as defined by RECIST v1.1.
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ECOG PS ≤1.
Exclusion Criteria:
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visceral crisis at risk of life-threatening complications in the short term
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known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung functions.
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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 study.
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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.
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inflammatory breast cancer
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impaired cardiovascular function or clinically significant cardiovascular diseases
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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.
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renal impairment, not adequate liver function and/or bone marrow function
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known active infection
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Pfizer
- Arvinas Estrogen Receptor, Inc.
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- C4891006