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

NCT04072952 | Completed Phase 1 FDA Drug

• 2 other identifiers: ARV-471-mBC-101C4891019
• Study Type: interventional
• Target: 217
• Locations: 1 country
• Sites: 16

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.

Conditions

Breast Cancer

Keywords

Breast Cancer; Metastatic Breast Cancer; Malignant Neoplasm of the Breast; mBC; ER+/HER2-; Locally Advanced Breast Cancer; ARV-471; Vepdegestrant; Palbociclib; Ibrance

Outcome Measures

Primary Outcomes (7)

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

  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

  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

  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

  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

  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

  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

  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 Outcomes (23)

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

  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).

  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).

  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).

  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

  through study completion, up to approximately 2 years

Study Arms (2)

ARV-471

EXPERIMENTAL

Parts A and B: ARV-471 administered once daily (QD) or twice daily (BID) for 28 day cycles.

Drug: ARV-471

ARV-471 and palbociclib (IBRANCE®)

EXPERIMENTAL

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®)

Interventions

ARV-471 DRUG

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

ARV-471

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

ARV-471 and palbociclib (IBRANCE®)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Arvinas Estrogen Receptor, Inc.: lead
• Pfizer: collaborator

Study Sites (16)

Clinical Trial Site

Palo Alto, California, 94304, United States

Location

Clinical Trial Site

San Francisco, California, 94158, United States

Location

Clinical Trial Site

Santa Monica, California, 90404, United States

Location

Clinical Trial Site

Norwalk, Connecticut, 06856, United States

Location

Clinical Trial Site

Fort Myers, Florida, 33901, United States

Location

Clinical Trial Site

Tampa, Florida, 33612, United States

Location

Clinical Trial Site

Chicago, Illinois, 60637, United States

Location

Clinical Trial Site

Boston, Massachusetts, 02114, United States

Location

Clinical Trial Site

Boston, Massachusetts, 02215, United States

Location

Clinical Trial Site

Ann Arbor, Michigan, 48109, United States

Location

Clinical Trial Site

St Louis, Missouri, 63110, United States

Location

Clinical Trial Site

East Brunswick, New Jersey, 08816, United States

Location

Clinical Trial Site

The Bronx, New York, 10461, United States

Location

Clinical Trial Site

Charlotte, North Carolina, 28204, United States

Location

Clinical Trial Site

Nashville, Tennessee, 37203, United States

Location

Clinical Trial Site

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 Recommended Phase 2 Dose (RP2D) including a combination cohort with palbociclib (IBRANCE®)

Study Record Dates

• First Submitted: August 27, 2019
• First Posted: August 28, 2019
• Study Start: August 5, 2019
• Primary Completion: September 13, 2024
• Study Completion: March 5, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)