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Completed

NCT Number: NCT04072952

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

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.

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Clinical Trial Site, Palo Alto, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 immunohistochemistry (IHC) testing and pharmacodynamics (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.

Treatment and study plan

ARV-471

Drug

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

ARV-471 in combination with palbociclib (IBRANCE®)

Drug

Part C: Daily oral dosages of ARV-471 for 28 days in combination with palbociclib (IBRANCE®) for 21 days

Primary outcomes

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

Secondary outcomes

  1. Part A: Assessment of pharmacokinetic (PK) 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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).

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  21. 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.

  22. 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.

  23. 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.

Sponsors and collaborators

Lead sponsor

Arvinas Estrogen Receptor, Inc.

Industry

Collaborators

  • Pfizer

Registry information

Official study title

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

Acronym: mBC

Important dates

Study start
2019
Primary completion
2024
Study completion
2026
First posted
Aug 28, 2019
Registry last updated
Apr 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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