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The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

Geo Regions

Category

Breast Cancer

Vepdegestrant (ARV-471)*

Vepdegestrant is an investigational compound. Its safety and efficacy have not been established. * Vepdegestrant is being co-developed with Arvinas.

Palbociclib

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

Phase 1 /2

NCT04072952

Active Not-enrolling

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Locations

United States

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Study design
Participant Group/Arm

EXPERIMENTAL: ARV-471

Parts A and B: ARV-471 administered QD or BID for 28 day cycles.

Intervention/Treatment

DRUG: ARV-471

Parts A and B: ARV-471 administered QD or BID for 28 day cycles.

Participant Group/Arm

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.

Intervention/Treatment

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

Study design table for Clinical Trial
Key eligibility criteria
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.
Key dates
Study start date
  • August 2019
Estimated Study Completion Date
  • March 2025
Key endpoints
Primary Outcome Measures
Outcome Measure

Part A: Incidence of Dose Limiting Toxicities of ARV-471

Measure Description

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

Time Frame

28 Days

Outcome Measure

Part A: Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-471

Measure Description

Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug.

Time Frame

First study drug dose through a minimum of 30 calendar Days After Last study drug administration

Outcome Measure

Part A: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-471

Measure Description

Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.

Time Frame

First study drug dose through a minimum of 30 calendar Days After Last study drug administration

Outcome Measure

Part B: Assessment of anti-tumor activity of ARV-471

Measure Description

Clinical benefit response rate based on the summation of CRs, PRs and stable disease of 24 weeks duration or longer

Time Frame

through study completion, up to approximately 2 years

Outcome Measure

Part C: Incidence of Dose Limiting Toxicities of combination ARV-471 + palbociclib

Measure Description

First cycle dose-limiting toxicities and determination of a maximum tolerated dose (MTD) if applicable among the doses evaluated

Time Frame

28 Days

Outcome Measure

Part C: Number of Patients with Adverse Events as a measure of safety and tolerability of combination ARV-471 + palbociclib

Measure Description

Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug combination

Time Frame

First study drug dose through a minimum of 30 calendar Days After Last study drug administration

Outcome Measure

Part C: Incidence of laboratory abnormalities as a measure of safety and tolerability of combination ARV-471 + palbociclib

Measure Description

Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing

Time Frame

First study drug dose through a minimum of 30 calendar Days After Last study drug administration

Primary Outcome Measures table for Clinical Trial
Secondary Outcome Measures:
Outcome Measure

Part A: Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC).

Measure Description

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.

Time Frame

At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471

Outcome Measure

Part A: Assessment of pharmacokinetic parameter maximum concentration (Cmax).

Measure Description

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.

Time Frame

At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471

Outcome Measure

Part A: Assessment of pharmacokinetic parameter minimum concentration (Cmin).

Measure Description

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.

Time Frame

At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471

Outcome Measure

Part A: Assessment of pharmacokinetic parameter time to maximum concentration (Tmax).

Measure Description

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.

Time Frame

At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471

Outcome Measure

Part A: Assessment of anti-tumor activity of ARV-471

Measure Description

Anti-tumor activity of ARV-471 will be assessed by evaluating overall response rate per RECIST 1.1.

Time Frame

through study completion, up to approximately 2 years

Outcome Measure

Part A: Assessment of anti-tumor activity of ARV-471

Measure Description

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.

Time Frame

through study completion, up to approximately 2 years

Outcome Measure

Part A: Assessment of anti-tumor activity of ARV-471

Measure Description

Anti-tumor activity of ARV-471 will be assessed by evaluating disease control rate (complete response, partial response, stable disease).

Time Frame

through study completion, up to approximately 2 years

Outcome Measure

Part A: Assessment of anti-tumor activity of ARV-471

Measure Description

Anti-tumor activity of ARV-471 will be assessed by evaluating progression free survival.

Time Frame

through study completion, up to approximately 2 years

Outcome Measure

Part A: Assessment of anti-tumor activity of ARV-471

Measure Description

Anti-tumor activity of ARV-471 will be assessed by evaluating duration of response.

Time Frame

through study completion, up to approximately 2 years

Outcome Measure

Part B: Assessment of anti-tumor activity of ARV-471

Measure Description

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.

Time Frame

through study completion, up to approximately 2 years

Outcome Measure

Part B: Assessment of anti-tumor activity of ARV-471

Measure Description

Anti-tumor activity of ARV-471 will be assessed by evaluating duration of response.

Time Frame

through study completion, up to approximately 2 years

Outcome Measure

Part B: Assessment of anti-tumor activity of ARV-471

Measure Description

Anti-tumor activity of ARV-471 will be assessed by evaluating progression-free survival.

Time Frame

through study completion, up to approximately 2 years

Outcome Measure

Part B: Assessment of anti-tumor activity of ARV-471

Measure Description

Anti-tumor activity of ARV-471 will be assessed by evaluating overall survival.

Time Frame

through study completion, up to approximately 2 years

Outcome Measure

Part B: Evaluation of Plasma Concentrations of ARV-471

Measure Description

To characterize the pre-dose 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]

Outcome Measure

Part B: Evaluation of Safety and Tolerability

Measure Description

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.

Time Frame

First study drug dose through a minimum of 30 calendar Days After Last study drug administration

Outcome Measure

Part B: Evaluation of Safety and Tolerability

Measure Description

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.

Time Frame

First study drug dose through a minimum of 30 calendar Days After Last study drug administration

Outcome Measure

Part C:Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC)

Measure Description

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.

Time Frame

At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products

Outcome Measure

Part C: Assessment of pharmacokinetic parameter maximum concentration (Cmax).

Measure Description

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

Time Frame

At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products

Outcome Measure

Part C: Assessment of pharmacokinetic parameter minimum concentration (Cmin).

Measure Description

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.

Time Frame

At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products

Outcome Measure

Part C: Assessment of pharmacokinetic parameter time to maximum concentration (Tmax)

Measure Description

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.

Time Frame

At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products

Outcome Measure

Part C: Assessment of anti-tumor activity of ARV-471 in combination with palbociclib

Measure Description

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.

Time Frame

through study completion, up to approximately 2 years

Outcome Measure

Part C: Assessment of anti-tumor activity of ARV-471 in combination with palbociclib

Measure Description

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.

Time Frame

through study completion, up to approximately 2 years

Outcome Measure

Part C: Assessment of anti-tumor activity of ARV-471 in combination with palbociclib

Measure Description

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.

Time Frame

through study completion, up to approximately 2 years

Secondary Outcome Measures table for Clinical Trial
Number of participants

217

Collaborators and investigators

Sponsor: Arvinas Estrogen Receptor, Inc.

Collaborator: Pfizer

This information is current as of May 6th 2024.

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When calling, please reference this study number:

More Information Close NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier. NCT04072952