A Phase 1/2 Trial of ARV-471 Alone and in Combination With Palbociclib (IBRANCE®) in Patients With ER+/HER2- Locally Advanced or Metastatic Breast Cancer (mBC)

June 2, 2023 updated by: Arvinas Estrogen Receptor, Inc.

A Phase 1/2, Open Label, Dose Escalation, and Cohort Expansion Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of ARV-471 Alone and in Combination With Palbociclib (IBRANCE®) in Patients With Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Locally Advanced or Metastatic Breast Cancer, Who Have Received Prior Hormonal Therapy and Chemotherapy in the Locally Advanced/Metastatic Setting

This is a Phase 1/2 dose escalation and cohort expansion study and will assess the safety, tolerability and anti-tumor activity of ARV-471 alone and in combination with palbociclib (IBRANCE®) in patients with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) locally advanced or metastatic breast cancer, who have received prior hormonal therapy and chemotherapy in the locally advanced/metastatic setting.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

215

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Clinical Trial Site
      • San Francisco, California, United States, 94158
        • Recruiting
        • Clinical Trial Site
      • Santa Monica, California, United States, 90404
        • Recruiting
        • Clinical Trial Site
    • Connecticut
      • Norwalk, Connecticut, United States, 06856
        • Recruiting
        • Clinical Trial Site
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Recruiting
        • Clinical Trial Site
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Clinical Trial Site
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • Clinical Trial Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Clinical Trial Site
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Clinical Trial Site
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • Clinical Trial Site
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Clinical Trial Site
    • New Jersey
      • East Brunswick, New Jersey, United States, 08816
        • Recruiting
        • Clinical Trial Site
    • New York
      • Bronx, New York, United States, 10461
        • Recruiting
        • Clinical Trial Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Recruiting
        • Clinical Trial Site
    • Tennessee
      • Knoxville, Tennessee, United States, 37909
        • Withdrawn
        • Clinical Trial Site
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Clinical Trial Site
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Clinical Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Part A, Part B, and Part C:

  • Patients at least 18 years of age at the time of signing the informed consent.
  • Patients must have histologically or cytologically confirmed ER+ and HER2- advanced breast cancer for which standard curative therapy is no longer effective or does not exist.
  • Patients must have measurable or non-measurable disease by RECIST criteria (version1.1), with radiologic tumor assessments performed within 28 days of the first dose of therapy.
  • Patients must be willing to undergo a core biopsy of accessible tumor within 4 weeks prior to the initiation of study treatment and a follow-up biopsy on treatment for ER IHC testing and PD studies. (Patients without accessible tumor tissue may be eligible after discussion with the Medical Monitor.)
  • Women must be postmenopausal due to surgical or natural menopause.

Part A:

- Patients must have received at least 2 prior endocrine regimens in any setting (neoadjuvant, adjuvant or advanced/metastatic) a CDK4/6 inhibitor and up to 3 prior regimens of cytotoxic chemotherapy in the locally advanced or metastatic setting.

Part B:

  • Patients must have received at least 1 prior endocrine regimen for a minimum of 6 months in the locally advanced or metastatic setting; if more than 1 prior endocrine regimen has been administered, only one of the regimens must have been administered for a minimum of 6 months in the locally advanced or metastatic setting
  • Patients must have received a CDK4/6 inhibitor
  • Patients must have received up to 1 prior regimen of cytotoxic chemotherapy in the locally advanced or metastatic setting
  • Women must be postmenopausal due to surgical or natural menopause.

Part C:

  • Patients must have received at least one prior endocrine regimen.
  • Patients must have received no more than two prior chemotherapy regimens for advanced disease.
  • Women must be postmenopausal due to surgical or natural menopause.

Exclusion Criteria:

Part A, Part B, and Part C:

  • Patients with known symptomatic brain metastases requiring steroids (above physiologic replacement doses). Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to first dose of study drug, have discontinued high-dose corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable as judged by the Investigator.
  • Receipt of prior anti-cancer or other investigational therapy within 14 days prior to the first administration of study drug.
  • Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to >25% of the bone marrow. Palliative radiation for the alleviation of pain due to bone metastasis will be allowed during the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ARV-471
Parts A and B: ARV-471 administered QD or BID for 28 day cycles.
Drug: ARV-471
Parts A and B: ARV-471 administered QD or BID for 28 day cycles.
Experimental: ARV-471 and palbociclib (IBRANCE®)
Part C: Daily oral dosages of ARV-471 for 28 days in combination with palbociclib (IBRANCE®) for 21 days.
Drug: ARV-471 in combination with palbociclib (IBRANCE®)
Part C: Daily oral dosages of ARV-471 for 28 days in combination with palbociclib (IBRANCE®) for 21 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Incidence of Dose Limiting Toxicities of ARV-471
Time Frame: 28 Days
First Cycle Dose limiting toxicities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug
28 Days
Part A: Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-471
Time Frame: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug.
First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Part A: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-471
Time Frame: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Part B: Assessment of anti-tumor activity of ARV-471
Time Frame: through study completion, up to approximately 2 years
Clinical benefit response rate based on the summation of CRs, PRs and stable disease of 24 weeks duration or longer
through study completion, up to approximately 2 years
Part C: Incidence of Dose Limiting Toxicities of combination ARV-471 + palbociclib
Time Frame: 28 Days
First cycle dose-limiting toxicities and determination of a maximum tolerated dose (MTD) if applicable among the doses evaluated
28 Days
Part C: Number of Patients with Adverse Events as a measure of safety and tolerability of combination ARV-471 + palbociclib
Time Frame: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug combination
First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Part C: Incidence of laboratory abnormalities as a measure of safety and tolerability of combination ARV-471 + palbociclib
Time Frame: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
First study drug dose through a minimum of 30 calendar Days After Last study drug administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC).
Time Frame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
Concentration-time curve (AUC) for single and multiple dose of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses.
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
Part A: Assessment of pharmacokinetic parameter maximum concentration (Cmax).
Time Frame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
Maximum concentration (Cmax) for single and multiple dose of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses.
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
Part A: Assessment of pharmacokinetic parameter minimum concentration (Cmin).
Time Frame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
Minimum concentration (Cmin) for single and multiple dose of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses.
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
Part A: Assessment of pharmacokinetic parameter time to maximum concentration (Tmax).
Time Frame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
Time to maximum concentration (Tmax) for single and multiple dose of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses.
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471
Part A: Assessment of anti-tumor activity of ARV-471
Time Frame: through study completion, up to approximately 2 years
Anti-tumor activity of ARV-471 will be assessed by evaluating overall response rate per RECIST 1.1.
through study completion, up to approximately 2 years
Part A: Assessment of anti-tumor activity of ARV-471
Time Frame: through study completion, up to approximately 2 years
Anti-tumor activity of ARV-471 will be assessed by evaluating clinical benefit response (CBR) rate based on the summation of complete responses (CRs), partial responses (PRs) and stable disease of 24 weeks duration or longer.
through study completion, up to approximately 2 years
Part A: Assessment of anti-tumor activity of ARV-471
Time Frame: through study completion, up to approximately 2 years
Anti-tumor activity of ARV-471 will be assessed by evaluating disease control rate (complete response, partial response, stable disease).
through study completion, up to approximately 2 years
Part A: Assessment of anti-tumor activity of ARV-471
Time Frame: through study completion, up to approximately 2 years
Anti-tumor activity of ARV-471 will be assessed by evaluating progression free survival.
through study completion, up to approximately 2 years
Part A: Assessment of anti-tumor activity of ARV-471
Time Frame: through study completion, up to approximately 2 years
Anti-tumor activity of ARV-471 will be assessed by evaluating duration of response.
through study completion, up to approximately 2 years
Part B: Assessment of anti-tumor activity of ARV-471
Time Frame: through study completion, up to approximately 2 years
Anti-tumor activity of ARV-471 will be assessed by evaluating overall response rate per RECIST 1.1 in patients with measurable disease at baseline.
through study completion, up to approximately 2 years
Part B: Assessment of anti-tumor activity of ARV-471
Time Frame: through study completion, up to approximately 2 years
Anti-tumor activity of ARV-471 will be assessed by evaluating duration of response.
through study completion, up to approximately 2 years
Part B: Assessment of anti-tumor activity of ARV-471
Time Frame: through study completion, up to approximately 2 years
Anti-tumor activity of ARV-471 will be assessed by evaluating progression-free survival.
through study completion, up to approximately 2 years
Part B: Assessment of anti-tumor activity of ARV-471
Time Frame: through study completion, up to approximately 2 years
Anti-tumor activity of ARV-471 will be assessed by evaluating overall survival.
through study completion, up to approximately 2 years
Part B: Evaluation of Plasma Concentrations of ARV-471
Time Frame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products]
To characterize the pre-dose concentrations of ARV-471.
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products]
Part B: Evaluation of Safety and Tolerability
Time Frame: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Further evaluation of safety and tolerability of ARV-471 will be based on adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug.
First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Part B: Evaluation of Safety and Tolerability
Time Frame: First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Further evaluation of safety and tolerability of ARV-471 will be based on Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
First study drug dose through a minimum of 30 calendar Days After Last study drug administration
Part C: Assessment of pharmacokinetic parameter minimum concentration (Cmin).
Time Frame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products
Minimum concentration (Cmin) for single and multiple dose of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses.
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products
Part C: Assessment of pharmacokinetic parameter time to maximum concentration (Tmax)
Time Frame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products
Time to maximum concentration (Tmax) for single and multiple dose of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses.
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products
Part C: Assessment of anti-tumor activity of ARV-471 in combination with palbociclib
Time Frame: through study completion, up to approximately 2 years
Anti-tumor activity of ARV-471 in combination with palbociclib will be assessed by evaluating overall response rate per RECIST 1.1 in patients with measurable disease at baseline.
through study completion, up to approximately 2 years
Part C: Assessment of anti-tumor activity of ARV-471 in combination with palbociclib
Time Frame: through study completion, up to approximately 2 years
Anti-tumor activity of ARV-471 in combination with palbociclib will be assessed by evaluating clinical benefit response (CBR) rate based on the summation of complete responses (CRs), partial responses (PRs) and stable disease of 24 weeks duration or longer.
through study completion, up to approximately 2 years
Part C: Assessment of anti-tumor activity of ARV-471 in combination with palbociclib
Time Frame: through study completion, up to approximately 2 years
Anti-tumor activity of ARV-471 in combination with palbociclib will be assessed by evaluating time to event endpoints: progression free survival, duration of response.
through study completion, up to approximately 2 years
Part C:Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC)
Time Frame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products
Concentration-time curve (AUC) for single and multiple doses of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses, and of palbociclib when given alone and in combination with ARV-471.
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products
Part C: Assessment of pharmacokinetic parameter maximum concentration (Cmax).
Time Frame: At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products
Maximum concentration (Cmax) for single and multiple doses of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses, and of palbociclib when given alone and in combination with ARV-471
At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Arvinas Estrogen Receptor, Inc.

Collaborators

Pfizer

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 5, 2019

Primary Completion (Estimated)

March 25, 2024

Study Completion (Estimated)

September 25, 2024

Study Registration Dates

First Submitted

August 27, 2019

First Submitted That Met QC Criteria

August 27, 2019

First Posted (Actual)

August 28, 2019

Study Record Updates

Last Update Posted (Actual)

June 5, 2023

Last Update Submitted That Met QC Criteria

June 2, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARV-471-mBC-101
  • C4891019 (Other Identifier: Pfizer)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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