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A Phase I Study of Anti-CD3 x Cetuximab-Armed Activated T Cells, Low Dose IL-2, and GM-CSF for EGFR-Positive, Advanced Non-Small Cell Lung Cancer

Phase 1
18 Years
Open (Enrolling)
Lung Cancer

Thank you

Trial Information

A Phase I Study of Anti-CD3 x Cetuximab-Armed Activated T Cells, Low Dose IL-2, and GM-CSF for EGFR-Positive, Advanced Non-Small Cell Lung Cancer



- Determine the safety and maximum tolerated dose of EGFRBi-armed autologous activated
T-cells (ATC) when administered in combination with low-dose aldesleukin and
sargramostim (GM-CSF) in patients with recurrent, refractory, or extensive (metastatic)
non-small cell lung cancer (NSCLC).


- Assess clinical outcome based on tumor responses, overall survival, and
progression-free survival.

- Monitor changes in sera concentrations of the tumor marker in association with
EGFRBi-armed ATC administration throughout the study and at time points thereafter in
patients with elevated levels of carcinoembryonic antigen (CEA) prior to beginning the

- Monitor patient sera for human anti-mouse antibodies (HAMA).

- Evaluate immune response, which may reflect immune augmentation in response to
EGFRBi-armed ATC infusions, in peripheral blood mononuclear cell (PBMC) samples as well
as purified immune cell populations.

- Investigate proliferation in response to ex vivo stimulation with NSCLC
tumor-associated antigens, sera cytokine profiles (Th1 vs Th2), cytotoxicity of patient
PBMC, and interferon gamma ELISPOTS as a surrogate marker for assessing generation of
EGFR-specific cytotoxic T-lymphocytes (CTL).

OUTLINE: Peripheral blood mononuclear cells (PBMCs) are collected by 1 or 2 leukaphereses
for the generation of activated T cells (ATCs). The PBMCs are activated with OKT3 (anti-CD3)
and expanded in aldesleukin for up to 14 days. The ATCs are then armed with EGFRBi.

Patients receive EGFRBi-armed autologous ATCs IV over 30-60 minutes twice weekly for 4 weeks
(a total of 8 infusions) in the absence of disease progression or unacceptable toxicity.
Patients also receive low-dose aldesleukin subcutaneously (SC) once daily and sargramostim
(GM-CSF) SC twice weekly beginning 3 days before the first ATC infusion and continuing for 1
week after the last ATC infusion.

After completion of study therapy, patients are followed periodically.

Inclusion Criteria


- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

- Recurrent, refractory, or metastatic disease after ≥ 1 prior first-line regimen
(chemotherapy or radiotherapy)

- Documented EGFR-positive disease (any expression level) by immunohistochemistry (IHC)
(may be based on archival sample)

- Measurable or evaluable disease by radiograph, CT scan, MRI, and/or physical exam

- Appropriate slides of the primary lesion must be available for review of IHC staining
assessment by a central pathology team

- No clinical evidence of active brain metastases

- Patients with brain metastases are eligible provide they have received
definitive radiotherapy or chemotherapy and/or have undergone surgical resection
for brain metastases

- No prior hematological malignancy


- Karnofsky performance status (PS) 60-100% OR ECOG PS 0-2

- Life expectancy ≥ 3 months

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Granulocytes ≥ 1,000/mm^3

- Platelet count ≥ 50,000/mm^3

- Hemoglobin ≥ 8 g/dL

- BUN ≤ 2.0 times normal

- Serum creatinine ≤ 2.0 mg/dL

- Bilirubin ≤ 1.5 times normal

- SGOT ≤ 1.5 times normal (with or without liver metastases)

- Hepatitis B surface antigen and HIV negative

- LVEF ≥ 45 % at rest (by MUGA)

- No evidence of depressed left ventricular function

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

- No other malignancy, except for the following:

- History of curatively treated in situ squamous cell carcinoma or basal cell
carcinoma of the skin

- History of other curatively treated malignancy (except those with a hematologic
origin) for which the patient has remained in complete remission > 5 years after
completing therapy (as documented by history, physical exams, tumor markers, and
radiology scanning)

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

- No recent myocardial infarction (within the past year)

- No current angina/coronary symptoms requiring medications

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

- No systolic blood pressure (BP) ≥ 130 mm Hg or diastolic BP ≥ 80 mm Hg

- Patients with elevated BP must have it controlled by anti-hypertensive
medications for at least 7 days prior to the first infusion


- See Disease Characteristics

- More than 4 weeks since prior chemotherapy or radiotherapy

- At least 4 weeks since prior cetuximab or small molecule EGFR-inhibitors including,
but not limited to, gefitinib or erlotinib hydrochloride

- No concurrent radiotherapy

- No concurrent steroids except for treatment of adrenal failure, septic shock, or
pulmonary toxicity or hormones for non-disease-related conditions (e.g., insulin for

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Outcome Time Frame:

4 weeks

Safety Issue:


Principal Investigator

Abby Maizel, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Roger Williams Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

November 2007

Completion Date:

December 2013

Related Keywords:

  • Lung Cancer
  • recurrent non-small cell lung cancer
  • stage IV non-small cell lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Roger Williams Medical Center Providence, Rhode Island  02908-4735