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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04072952
Recruitment Status : Recruiting
First Posted : August 28, 2019
Last Update Posted : May 18, 2022
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Arvinas Inc. ( Arvinas Estrogen Receptor, Inc. )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: ARV-471 Drug: ARV-471 in combination with palbociclib (IBRANCE®) Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 215 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Subsequent dose level is determined by the Cohort Review Committee after the initial starting dose cohort and each subsequent dose cohort completes the first 28 days of treatment

Dose escalation followed by expansion at a RP2D including a combination cohort with palbociclib (IBRANCE®)

Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : August 5, 2019
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Palbociclib

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




Primary Outcome Measures :
  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 Outcome Measures :
  1. 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.

  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 dose of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses.

  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 dose of ARV-471 PK parameters will be assessed when applicable after a single dose and after multiple doses.

  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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04072952


Contacts
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Contact: Arvinas Estrogen Receptor, Inc. 475-345-3366 clinicaltrialsARV-471@arvinas.com

Locations
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United States, California
Clinical Trial Site Recruiting
Palo Alto, California, United States, 94304
Clinical Trial Site Recruiting
San Francisco, California, United States, 94158
Clinical Trial Site Recruiting
Santa Monica, California, United States, 90404
United States, Connecticut
Clinical Trial Site Recruiting
Norwalk, Connecticut, United States, 06856
United States, Florida
Clinical Trial Site Recruiting
Fort Myers, Florida, United States, 33901
Clinical Trial Site Recruiting
Tampa, Florida, United States, 33612
United States, Illinois
Clinical Trial Site Recruiting
Chicago, Illinois, United States, 60637
United States, Massachusetts
Clinical Trial Site Recruiting
Boston, Massachusetts, United States, 02114
Clinical Trial Site Recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
Clinical Trial Site Recruiting
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Clinical Trial Site Recruiting
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Clinical Trial Site Recruiting
East Brunswick, New Jersey, United States, 08816
United States, New York
Clinical Trial Site Recruiting
Bronx, New York, United States, 10461
United States, North Carolina
Clinical Trial Site Recruiting
Charlotte, North Carolina, United States, 28204
United States, Tennessee
Clinical Trial Site Recruiting
Knoxville, Tennessee, United States, 37909
Clinical Trial Site Recruiting
Nashville, Tennessee, United States, 37203
United States, Washington
Clinical Trial Site Recruiting
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Arvinas Estrogen Receptor, Inc.
Pfizer
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Responsible Party: Arvinas Estrogen Receptor, Inc.
ClinicalTrials.gov Identifier: NCT04072952    
Other Study ID Numbers: ARV-471-mBC-101
First Posted: August 28, 2019    Key Record Dates
Last Update Posted: May 18, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Arvinas Inc. ( Arvinas Estrogen Receptor, Inc. ):
Breast Cancer
Metastatic Breast Cancer
Malignant Neoplasm of the Breast
mBC
ER+/HER2-
Locally Advanced Breast Cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Palbociclib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action