The AVIATOR Study: Trastuzumab and Vinorelbine With Avelumab OR Avelumab & Utomilumab in Advanced HER2+ Breast Cancer

NCT03414658 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: 17-455TBCRC045
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 17

Brief Summary

This research study is studying a combination of drugs as a possible treatment for breast cancer. The drugs involved in this study are:

• Group A: Trastuzumab (Herceptin) + Vinorelbine (Navelbine)
• Group B: Trastuzumab + Vinorelbine + Avelumab
• Group C: Trastuzumab + Vinorelbine + Avelumab + Utomilumab (PF-05082566)

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Progression Free Survival is defined from the time from randomization to the first occurrence of disease progression as determined by the investigator using RECIST 1.1 or death from any cause, whichever occurs first.

  2 years

Secondary Outcomes (3)

• Objective Response Rate

  2 years

• Duration of Response

  3 years

• Overall Survival

  5 years

Study Arms (3)

NH: Trastuzumab + Vinorelbine

EXPERIMENTAL

* Trastuzumab is administered intravenously twice per cycle * Vinorelbine is administered intravenously 3 times per cycle

Drug: Vinorelbine; Drug: Trastuzumab

NHA: Trastuzumab + Vinorelbine + Avelumab

EXPERIMENTAL

* Trastuzumab is administered intravenously twice per cycle * Vinorelbine is administered intravenously 3 times per cycle * Avelumab is administered intravenously twice per cycle * Antihistamine and with acetaminophen is mandatory 30 to 60 minutes prior to each dose of avelumab

Drug: Vinorelbine; Drug: Trastuzumab; Drug: Avelumab

NHAU: Trastuzumab + Vinorelbine + Avelumab + Utomilumab

EXPERIMENTAL

* Trastuzumab is administered intravenously twice per cycle * Vinorelbine is administered intravenously 3 times per cycle * Avelumab is administered intravenously twice per cycle * Antihistamine and with acetaminophen is mandatory 30 to 60 minutes prior to each dose of avelumab * Utomilumab is administered intravenously once per cycle

Drug: Vinorelbine; Drug: Trastuzumab; Drug: Avelumab; Drug: Utomilumab

Interventions

Vinorelbine DRUG

work by interfering with cell division, which leaves the tumor unable to grow and spread

NH: Trastuzumab + Vinorelbine; NHA: Trastuzumab + Vinorelbine + Avelumab; NHAU: Trastuzumab + Vinorelbine + Avelumab + Utomilumab

Trastuzumab DRUG

trastuzumab induces an antibody-dependent cell-mediated cytotoxicity against tumor cells that overexpress HER2.

NH: Trastuzumab + Vinorelbine; NHA: Trastuzumab + Vinorelbine + Avelumab; NHAU: Trastuzumab + Vinorelbine + Avelumab + Utomilumab

Avelumab DRUG

monoclonal antibody directed against the human immunosuppressive ligand programmed death-ligand 1 (PD-L1) protein

NHA: Trastuzumab + Vinorelbine + Avelumab; NHAU: Trastuzumab + Vinorelbine + Avelumab + Utomilumab

Utomilumab DRUG

Utomilumab is an antibody designed to stimulate the body's immune system to fight cancer cells

NHAU: Trastuzumab + Vinorelbine + Avelumab + Utomilumab

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years or older
• Histologically confirmed breast adenocarcinoma that is unresectable loco-regionally advanced or metastatic
• HER2-positive (immunohistochemistry score 3+) or ERBB2- amplification (Ratio ERBB2/centromeres ≥ 2.0 or mean gene copy number ≥ 6) on primary tumor or of metastatic or unresectable loco-regional biopsy.
• Measurable disease per RECIST v1.1 (see Section 11)
• Patients must have previous treatment with ado-trastuzumab emtansine (Kadcyla, T-DM1) in any setting. Patients must have previously received trastuzumab and pertuzumab in the metastatic setting or within 12 months of neoadjuvant/adjuvant treatment.
• Patient must have progressed on their most recent line of therapy. Progression must have been demonstrated by radiological or clinical assessment.
• Left ventricular ejection fraction (LVEF) ≥ 50%
• Willingness and availability to submit FFPE tissue for central confirmation of HER2 positivity and central assessment of PD-L1 status. This can be from archival tissue from unresectable loco-regional or metastatic disease obtained ≤ 1 year prior to enrollment or new tissue material from a recently obtained surgical or diagnostic biopsy. Tissue obtained for the biopsy must not have been previously irradiated. If a patient does not have any available archival tissue ≤ 1 year old and the treating investigator does not feel that it would be safe to perform a fresh biopsy, the requirement for a fresh biopsy may be waived after discussion with the Principal Investigator.
• Written informed consent for screening and trial participation procedures including biological material transfer and handling.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Hematopoietic status:
• Absolute neutrophil count ≥ 1.0 × 109/L,
• Platelet count ≥ 100 × 109/L,
• Hemoglobin ≥ 9 g/dL
• Hepatic status:

You may not qualify if:

• Prior therapy with any anti-PD-1, anti-PD-L1, L2, anti-4-1BB (CD137), or anti-CTLA4 therapy
• Known Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
• Positive for Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA \[qualitative\]).
• History of interstitial lung disease
• Active central nervous system metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (patients with history of CNS metastases or spinal cord compression are eligible if they are clinically stable for at least 4 weeks before first dose of investigational product and do not require high-dose steroid treatment).
• History of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association functional classification ≥3), angina, myocardial infarction or ventricular arrhythmia.
• Previous severe hypersensitivity reaction to treatment with another monoclonal antibody.
• Active infection requiring systemic therapy.
• Chronic systemic therapy with immunosuppressive agents including corticosteroids.
• Active autoimmune disease or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the trial. Patients with hypothyroidism stable on hormone replacement or Sjögren's syndrome will not be excluded from the trial.
• Concurrent disease or condition that would make the patient inappropriate for trial participation or any serious medical disorder that would interfere with the patient's safety.
• No uncontrolled hypertension (≥180/110), unstable diabetes mellitus, dyspnea at rest, or chronic therapy with oxygen.
• Chemotherapy, radiotherapy, and/or biological cancer therapy within 3 weeks prior to the first trial dose or has not recovered to CTCAE v.4 grade 1 or better from adverse events (except alopecia).
• Unresolved or unstable, serious adverse events from prior administration of another investigational drug.
• Live vaccines within 30 days prior to the first dose of trial therapy and during trial treatment.

Sponsors & Collaborators

• Adrienne G. Waks: lead
• Pfizer: collaborator
• Breast Cancer Research Foundation: collaborator
• Johns Hopkins University: collaborator

Study Sites (17)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

University of California San Francisco

San Francisco, California, 94158, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

University of Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7305, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Washington Fred Hutchinson Cancer Care

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Vinorelbine; Trastuzumab; avelumab; utomilumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Adrienne G. Waks, MD
• Organization: Dana-Farber Cancer Institute

Adrienne_Waks@dfci.harvard.edu

617-632-3800

Study Officials

• Adrienne Waks, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 10, 2017
• First Posted: January 30, 2018
• Study Start: June 21, 2018
• Primary Completion: May 1, 2023
• Study Completion (Estimated): May 31, 2026
• Last Updated: July 2, 2025
• Results First Posted: April 18, 2024

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)