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

  • End date
    May 31, 2025
  • participants needed
  • sponsor
    Adrienne G. Waks
Updated on 4 October 2022
measurable disease
tumor cells
primary tumor
breast adenocarcinoma
her2/neu-positive breast cancer


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)


This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug combination to learn whether the drug combination works in treating a specific disease. "Investigational" means that drug combination is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved Utomilumab as a treatment for any disease.

The FDA (the U.S. Food and Drug Administration) has approved Avelumab as a treatment for other diseases.

The FDA (the U.S. Food and Drug Administration) has approved trastuzumab as a treatment option for this disease.

The FDA (the U.S. Food and Drug Administration) has approved vinorelbine as a treatment for other diseases and is commonly used as a treatment option for this disease.

The immune system is the body's natural defense against disease. The immune system sends a type of cells called T cells throughout the body to detect and fight infections and diseases-including cancers. One way the immune system controls the activity of T cells is through the PD-1 (programmed cell death protein-1) pathway. However, some cancer cells hide from T-cell attack by taking control of the PD-1 pathway and this stops T cells from attacking cancer cells. Avelumab is a type of drug, known as an antibody which is designed to block the PD-1 pathway and helps the immune system in detecting and fighting cancer cells. An antibody is a protein produced by the body's immune system when it detects harmful substances. Previous studies show that the administration of antibodies which block the PD-1 pathway can lead to tumor destruction.

Utomilumab is an antibody designed to stimulate the body's immune system to fight cancer cells. Previous studies have shown that the administration of this type of antibody may help to prevent tumors from growing.

In the laboratory, adding avelumab and Utomilumab to trastuzumab appears to improve effectiveness. It is not known whether this is true in humans.

In this research study, the investigators are evaluating the activity of 3 different combinations: (a)trastuzumab and vinorelbine combined, (b) trastuzumab, vinorelbine and avelumab combined, and (c) trastuzumab, vinorelbine, avelumab and utomilumab combined in participants with metastatic HER2- positive breast cancer.

Condition Breast Cancer
Treatment Trastuzumab, Avelumab, Utomilumab, Vinorelbine
Clinical Study IdentifierNCT03414658
SponsorAdrienne G. Waks
Last Modified on4 October 2022


Yes No Not Sure

Inclusion Criteria

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
Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN). In the case of known Gilbert's syndrome, a higher serum total bilirubin (< 2 × ULN) is allowed
AST and ALT ≤ 2.5 × ULN; if the patient has liver metastases, ALT and AST must be ≤ 5 × ULN
Renal status
Creatinine ≤ 1.5 ×ULN or creatinine clearance > 60 ml/min
Proteinuria < 1 g/day
International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN unless
If female of childbearing potential, must have a negative pregnancy test within 7 days of initiating treatment. Childbearing potential is defined by: those who have not been surgically sterilized and/or have had a menstrual period in the past year
patient is receiving anticoagulant therapy as long as PT or PTT is within
Participants of childbearing potential (as defined above) must be willing to use effective contraception during treatment and up to 7 months after stop of trial treatment. Acceptable methods of contraception are intrauterine devices, bilateral tubal occlusion, vasectomized, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not allowed
therapeutic range of intended use of anticoagulant
Must not be breastfeeding/lactating

Exclusion Criteria

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)
Previous severe hypersensitivity reaction to treatment with another monoclonal antibody
Active infection requiring systemic therapy
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
Chronic systemic therapy with immunosuppressive agents including corticosteroids
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
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
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
No uncontrolled hypertension (≥180/110), unstable diabetes mellitus, dyspnea at rest, or chronic therapy with oxygen
Live vaccines within 30 days prior to the first dose of trial therapy and during trial treatment
Clear my responses

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Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

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