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A Phase II Study of Anti-CD3 x Anti-HER2/Neu Armed Activated T Cells After Second Line Chemotherapy in Women With HER2/Neu (0, 1+ or 2+) Metastatic Breast Cancers

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

A Phase II Study of Anti-CD3 x Anti-HER2/Neu Armed Activated T Cells After Second Line Chemotherapy in Women With HER2/Neu (0, 1+ or 2+) Metastatic Breast Cancers


- To determine whether treatment with anti-CD3 x anti-HER2/neu bispecific antibody-armed
activated T-cells (ATC) after second-line chemotherapy and lymphodepletion using
cyclophosphamide improves median progression-free survival (PFS) by 3 months beyond the
median PFS of 6 months reported in published trials in women with HER2/neu-negative
metastatic breast cancer.

- To confirm the toxicity profile of anti-CD3 x anti-HER2/neu bispecific antibody-armed
ATC given after second-line chemotherapy and lymphodepletion using cyclophosphamide in
these patients.

- To measure functional and phenotypic changes in immune cell populations in blood and
tumor samples (if accessible) as a consequence of immunotherapy (i.e., cytokine
responses, phenotypic markers of differentiation, and antitumor cytotoxicity).

- To develop correlates between systemic or tumor site immune responses and clinical

OUTLINE: Patients receive second-line chemotherapy for 4 courses or 4 months. Beginning 4
weeks after completion of chemotherapy, patients receive 1 dose of lymphodepleting
chemotherapy comprising cyclophosphamide IV on day -7. Beginning on day 0, patients receive
an infusion of anti-CD3 x anti-HER2/neu bispecific antibody-armed activated T-cells (ATC) IV
over 30-60 minutes once a week for 3 weeks. Patients then receive a boost of anti-CD3 x
anti-HER2/neu bispecific antibody-armed ATC at 12 weeks after the 3rd ATC infusion.

Blood and tumor tissue samples may be collected periodically for biomarker and other

After completion of study therapy, patients are followed up periodically for ≥ 2 years.

Inclusion Criteria


- Histologically or cytologically confirmed metastatic breast cancer

- All histological types allowed

- Recurrent disease after first-line chemotherapy in the metastatic setting, as defined
by 1 of the following:

- No objective response after administration of ≥ 4 courses of first-line

- Progression while receiving first-line chemotherapy without experiencing any
transient improvement

- Brief objective response to first-line chemotherapy with subsequent progression
while receiving the same therapy or within 12 months after the last dose of

- Patients who just started second line chemotherapy within 1 month allowed provided
there is no documented progressive disease on the second line chemotherapy

- HER2/neu-negative disease, defined as 0-2+ by IHC and/or FISH ratio (HER2 gene
signals to chromosome 17 signals) ≤ 2.2

- No HER2 overexpression by IHC or overamplification by FISH, as defined by any of
the following:

- 3+ IHC (uniform, intense membrane staining of > 30% of invasive tumor

- FISH result of > 6 HER2 gene copies per nucleus

- FISH ratio > 2.2

- Measurable or evaluable metastatic disease as documented by radiograph, CT scan,
PET/CT scan, MRI, bone scan, or physical exam

- At least 1 bidimensionally measurable lesion (that has not been irradiated) with
a minimum size in at least one diameter of ≥ 20 mm for liver lesions and ≥ 10 mm
for lung, skin, and lymph node metastases

- Biopsy of recurrent site(s) is not required

- No clinical evidence of active CNS metastases

- Patients with treated brain metastases (i.e., those who have received definitive
radiotherapy, chemotherapy, and/or surgical resection) are eligible

- Hormone receptor status not specified


- Menopausal status not specified

- Karnofsky performance status 70-100%

- Life expectancy ≥ 3 months

- Granulocytes ≥ 1,000/mm³

- Platelet count ≥ 50,000/mm³

- Hemoglobin ≥ 8 g/dL

- BUN ≤ 1.5 times normal

- Serum creatinine < 1.8 mg/dL

- Creatinine clearance ≥ 60 mL/min

- Bilirubin < 1.5 times normal

- ALT and AST < 5 times upper limit of normal (ULN)

- Alkaline phosphatase < 5 times ULN

- LVEF ≥ 45% at rest by MUGA or ECHO

- FEV_1, DLCO, and FVC ≥ 50% of predicted

- Negative pregnancy test

- No HIV positivity

- No myocardial infarction within the past year

- No current coronary symptoms requiring medications and/or evidence of depressed left
ventricular function (LVEF < 45% by MUGA or ECHO)

- No clinical evidence of congestive heart failure requiring medical management
(irrespective of MUGA/ECHO results)

- Patients whose systolic BP is consistently ≥ 140 mm Hg or diastolic BP is
consistently ≥ 80 mm Hg are eligible provided their BP is controlled by
antihypertensive medications for ≥ 7 days before the first activated T-cell infusion

- No other malignancy within the past 5 years except for basal cell skin carcinoma and
carcinoma in situ of the cervix

- No serious medical or psychiatric illness that would preclude informed consent or
intensive treatment


- See Disease Characteristics

- No more than 3 prior chemotherapy regimen for metastatic disease

- Prior taxanes, anthracyclines, or any other chemotherapy allowed

- No hormonal therapy within 2 weeks before leukapheresis

- No radiotherapy to the axial skeleton within 4 weeks before leukapheresis

- No concurrent steroids except those administered for adrenal failure, septic shock,
or pulmonary toxicity or hormones administered for nondisease-related conditions
(e.g., insulin for diabetes)

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Outcome Description:

30 evaluable patients will be accrued in this study. There will be a two-stage phase II design, 19 patients will be accrued in the first stage. During the 1st stage, if there are 4 or fewer progression-free patients at the 1 year follow-up, then the trial will conclude early for lack of efficacy. Otherwise, 11 add'l patients will be accrued for the 2nd stage.

Outcome Time Frame:

At one year follow up

Safety Issue:


Principal Investigator

Lawrence Lum, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Barbara Ann Karmanos Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

February 2011

Completion Date:

Related Keywords:

  • Breast Cancer
  • HER2-negative breast cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • Breast Neoplasms



Barbara Ann Karmanos Cancer Institute Detroit, Michigan  48201