Agatolimod and Trastuzumab in Treating Patients With Locally Advanced or Metastatic Breast Cancer


Bhuvaneswari Ramaswamy

Status and phase

Phase 2


Breast Cancer


Other: Correlative Studies
Drug: Trastuzumab
Drug: PF03512676

Study type


Funder types



NCI-2011-03157 (Registry Identifier)

Details and patient eligibility


RATIONALE: Biological therapies, such as agatolimod, may stimulate the immune system in different ways and stop tumor cells from growing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving agatolimod together with trastuzumab may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving agatolimod together with trastuzumab works in treating patients with locally advanced or metastatic breast cancer.

Full description

OBJECTIVES: Primary To evaluate the progression-free survival of patients with HER2-overexpressing locally advanced or metastatic breast cancer treated with trastuzumab (Herceptin®) and agatolimod sodium. Secondary To determine if agatolimod sodium augments antibody-mediated cytoxicity (ADCC) against trastuzumab-coated target cells by evaluating the ability of patient immune-effector cells to conduct ADCC and produce interferon gamma. OUTLINE: This is a multicenter study. Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Patients also receive agatolimod sodium subcutaneously on days 15 and 22 of course 1 and on days 1, 8, 15, and 22 of all subsequent courses. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for correlative laboratory studies. Samples are analyzed for antibody-mediated cytotoxicity (ADCC) by chromium-release assay; IFN-γ production and quantification by flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR); and levels of cytokines (IFN-γ and TNF-α) by ELISA. After completion of study therapy, patients are followed periodically.


6 patients




18+ years old


No Healthy Volunteers

Inclusion and exclusion criteria


  • Histologically or cytologically confirmed breast cancer

    • Locally advanced or metastatic disease
  • HER2-overexpressing tumor, defined as 3+ overexpression by IHC and/or HER2 amplified by FISH

  • Non-measurable disease allowed

  • Achieved partial response, complete response, or stable disease (i.e., no disease progression for ≥ 12 weeks) while on trastuzumab (Herceptin®) and chemotherapy, hormonal therapy alone, or trastuzumab alone

    • Last dose of trastuzumab must have been administered within the past 16 weeks
  • No unstable brain metastases

    • Patients with brain metastases are eligible provided they have been stable for ≥ 1 month after surgery or radiotherapy/radiosurgery AND off corticosteroids and anticonvulsants for ≥ 4 weeks
  • Hormone receptor status unspecified


  • ECOG(Eastern Cooperative Oncology Group)performance status (PS) 0-2 (Karnofsky PS 70-100%)
  • Absolute neutrophil count ≥ 1,500/mm³
  • Hemoglobin > 8 g/dL (transfusion/epoetin alfa allowed)
  • Platelet count ≥ 100,000/mm³
  • Total bilirubin < 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN (≤ 5.0 times ULN if known liver metastases)
  • Creatinine < 2 mg/mL
  • Ejection fraction ≥ 50% by echocardiogram or MUGA
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception before, during, and for ≥ 3 months after completion of study treatment
  • No ongoing or active infection requiring oral or IV antibiotics
  • No known autoimmune disorders or antibody-mediated disorders
  • No known HIV positivity
  • No known history of hepatitis B or C (active and/or previously treated)
  • No other malignancies within the past 5 years except nonmelanoma skin cancer or cervical cancer in situ
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs


  • See Disease Characteristics
  • More than 12 weeks since prior chloroquine
  • More than 4 weeks since prior growth factors
  • More than 4 weeks since prior systemic corticosteroids
  • More than 4 weeks since prior chemotherapy, radiotherapy, or monoclonal antibody therapy (except trastuzumab)
  • No prior agatolimod sodium
  • No prior allogeneic stem cell transplantation
  • No prior continuous treatment with single-agent trastuzumab for > 6 months
  • No more than 3 prior chemotherapy regimens for metastatic breast cancer
  • Any number of prior hormonal therapies allowed
  • No other concurrent investigational agents or monoclonal antibodies
  • No other concurrent anticancer agents or therapies
  • Concurrent bisphosphonates for skeletal metastasis allowed

Trial design

Primary purpose




Interventional model

Single Group Assignment


None (Open label)

6 participants in 1 patient group

Arm I: Treatment (PF03512676 in combination with Trastuzumab)
Experimental group
12 weekly treatments. Week 1-12 patients will receive Trastuzumab 2mg/kg IV(intervenous infusion). Patients who have not been treated wih Trastuzumab within 4 weeks will receive a loading dose of 4 mg/kg on week 1 and PF-03512676-0.16 mg/kg subcutaneous injection.Correlative studies will be drawn on week 1, 2, 6, 12 and 18.
Drug: PF03512676
Drug: Trastuzumab
Other: Correlative Studies

Trial contacts and locations



Data sourced from

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