A Phase I Study of Anti-CD3 x Cetuximab-Armed Activated T Cells, Low Dose IL-2, and GM-CSF for EGFR-Positive, Advanced Solid Tumors
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) advanced solid tumors.
Assess clinical outcome based on tumor responses, overall survival, and progression-free
Monitor changes in sera concentrations of the tumor-associated biomarkers respective of the
primary neoplasm (i.e. carcinoembryonic antigen(CEA); prostate specific antigen (PSA);
Her2/neu (HER2); etc.) in association with EGFRBi-armed ATC administration throughout the
study and at time points thereafter.
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 tumor-specific 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
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.
NOTE: For the purpose of determining safety and maximum tolerated dose of EGFRBi-armed ATC,
patients enrolled at each dose level from this study will be combined with patients enrolled
at each dose level in RWH 349-32 (NCT00569296): 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 (NSCLC) to count toward each dose level cohort. A total of three
patients enrolled form either of the two trials will be treated at each dose level, but at
least one NSCLC patient representative from protocol 349-32 will be enrolled and evaluated
at each dose level.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of EGFRBi-armed autologous activated T-cells
5 week regimen with 2 month follow up
Abby Maizel, MD,PhD
Roger William Medical Center
United States: Food and Drug Administration
|Roger Willaims Medical Center||Providence, Rhode Island 02908|