4-1BB Agonist Monoclonal Antibody PF-05082566 With Trastuzumab Emtansine or Trastuzumab in Treating Patients With Advanced HER2-Positive Breast Cancer

Not Recruiting

Trial ID: NCT03364348


This trial studies the best dose and side effects of utomilumab (4-1BB agonist monoclonal antibody PF-05082566) with trastuzumab emtansine or trastuzumab in treating patients with HER2-positive breast cancer that has spread to other places in the body. Monoclonal antibodies, such as utomilumab, trastuzumab emtansine, and trastuzumab may interfere with the ability of tumor cells to grow and spread.

Official Title

A Phase 1B Dose Escalation Trial of Human Anti 4 1BB Agonistic Antibody Utomilumab (PF 05082566) in Combination With Ado Trastuzumab Emtansine or Trastuzumab in Patients With HER2 Postive Advanced Breast Cancer



   - History of biopsy proven HER2 overexpressing breast cancer and radiographic evidence
   of metastatic disease, or locally recurrent unresectable disease. The HER2 status can
   be determined either by immunohistochemistry (IHC) [IHC score, 3+] or by fluorescence
   in situ hybridization (FISH) [as defined by HER2/CEP 17 ratio ≥ 2.0, or HER2 copy
   number ≥ 6], or as otherwise defined by 2018 ASCO/CAP guidelines.

   - Cohort 1 subjects must have received trastuzumab and a taxane separately or in
   combination (those who previously received ado-trastuzumab emtansine may accrue to
   Cohort 2).

   - Subjects in Cohort 2 must have received at least 1 prior therapy including
   ado-trastuzumab emtansine.

   - Subjects who discontinued prior trastuzumab or ado trastuzumab emtansine due to
   progressive or refractory disease are eligible for enrollment

   - Available tumor samples. For eligibility, if no unstained slides remain, stained
   pathology slides may be reviewed at the treating institution. However, a tumor sample
   is required for research evaluations per the following (any of Item 1; 2; or 3, in
   order of preference).

   - A FFPE tumor tissue block from a de novo fresh tumor biopsy obtained during screening
   will be requested, though not mandated.

   - A recently obtained archival FFPE tumor tissue block (or 10 to 15 unstained slides)
   from a primary or metastatic tumor resection or biopsy if the following criteria are

   - The biopsy or resection was performed within 1 year of enrollment OR

   - The subject has not received any intervening systemic anti cancer treatment from the
   time the tissue was obtained and enrolled onto the current study. OR

   - Any archival FFPE tumor tissue block (or unstained slides) from primary tumor
   resection specimen (if not provided per above). The archival sample may have been
   collected at any time prior to the current study, regardless of any intervening
   therapy. If an FFPE tissue block cannot be provided, a minimum of 10 unstained slides
   (15 preferable) will be acceptable.

   - Subjects must have evaluable OR measurable disease, as defined by RECIST v1.1.

   - Performance status 0 to 1 (by Eastern Cooperative Oncology Group [ECOG] scale).

   - Laboratory parameters (must satisfy all): Absolute neutrophil count (ANC) ≥ 1.5 ×
   109/L (≥ 1500/µL) Platelet count ≥ 100 × 109/L (≥ 100,000 /µL) Hemoglobin ≥ 9.0 g/dL;
   subjects on therapeutic anticoagulation are eligible if there is no bleeding and they
   are on a stable dose of anticoagulation therapy (eg, on Coumadin with an INR of 2 to
   3) for at least 7 days before registration (prior to the start of therapy, or stable
   heparin or Factor Xa inhibitor dose) Serum creatinine ≤ 1.5 × the ULN or calculated
   creatinine clearance (by Cockcroft Gault formula) ≥ 60 mL/min Aspartate
   aminotransferase (AST) ≤ 2.5 × ULN Alanine aminotransferase (ALT) ≤ 2.5 × ULN
   Bilirubin ≤ 1.5 × ULN

   - Subjects must not be pregnant or breastfeeding. A pregnancy test will be obtained if
   the subject is a woman of child bearing potential, defined as a sexually mature woman
   who has not undergone a hysterectomy or and/or bilateral oophorectomy or who has not
   been naturally postmenopausal for at least 24 consecutive months (ie, who has had
   menses at any time in the preceding 24 consecutive months) with 2 pregnancy tests, one
   at screening, and another immediately preceding the initiation of treatment.

   - Subjects must have signed an informed consent document stating that they understand
   the investigational nature of the proposed treatment

   - Left ventricular ejection fraction determined by echocardiogram or multiple gated
   acquisition scan (MUGA) (cardiac scan) must be 50% or higher.


   - Previously discontinued either trastuzumab or ado trastuzumab emtansine due to

   - Received any other investigational agents within 30 days of registration.

   - Central nervous system (CNS) metastases, unless previously treated by either radiation
   therapy and/or surgical resection, clinically stable for at least 60 days and on a
   stable corticosteroid dose of ≤ 4 mg/day decadron (or equivalent steroid regimen) for
   at least 1 month. Subjects with a history of CNS metastases that are both treated and
   stably controlled are eligible if all of the following apply:

   - Therapy has been administered (surgery and/or radiation therapy);

   - There is no additional treatment planned for brain metastases;

   - The subject is clinically stable;

   - The subject is on a stable corticosteroid dose of ≤ 4 mg/day decadron (or equivalent
   steroid regimen) for at least 1 month.

   - Prior malignancy (other than in situ cervical cancer, or basal cell or squamous cell
   carcinoma of the skin), unless treated with curative intent and without evidence of
   disease for 3 years or longer

   - Administration of other prior anticancer therapies within 4 weeks of enrollment,
   except ongoing administration of a bisphosphonate drug or denosumab as treatment for
   bone metastasis

   - Toxicities related to prior anticancer treatment (except alopecia) that have not
   resolved to ≤ Grade 1 according to common terminology criteria for adverse events
   (CTCAE v5) before registration or prior to start of therapy

   - Currently receiving systemic antibiotic, antiviral, or antifungal therapy for the
   treatment of an active infection

   - Systemic corticosteroid therapy at doses of greater than prednisone 5 mg daily (or
   dose-equivalent chronic steroid regimen) for therapeutic and not adrenal replacement
   indications (maintenance steroid use for adrenal insufficiency is permitted). Acute
   emergency administration, topical applications, inhaled sprays, eye drops or local
   injections of corticosteroids are allowed.

   - History of bleeding diathesis

   - Any co morbid medical condition deemed by the treating or principal investigator to
   possibly put the subject at significant risk for toxicity.

   - Subject has known sensitivity to any of the products to be administered during dosing

   - Subject has any kind of disorder that compromises the ability of the subject to give
   written informed consent and/or to comply with study procedures

   - Uncontrolled intercurrent illness including, but not limited to, symptomatic
   congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
   illness/social situations that would limit compliance with study requirements

   - History of venous thromboembolism within prior 6 months.

   - Subject with reproductive potential who will not agree to use, during the study and
   for 60 days after the last dose of utomilumab or 6 months for ado trastuzumab
   emtansine or trastuzumab 2 highly effective method of contraceptive such as:

   - Implants

   - Injectables

   - Intrauterine devices (IUDs) such as copper T or Levonorgestrel releasing intrauterine
   system (LNG IUS)

   - Sexual abstinence

   - Vasectomized partner

   - Condom or occlusive cap (diaphragm or cervical/vault cap) supplemented with the use of
   a spermicide during treatment


drug: Utomilumab

drug: Trastuzumab

drug: Ado-Trastuzumab Emtansine

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sinyoung Park

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