Trial of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) in patients with EGFR-expressing recurrent/metastatic non-small cell lung cancer (NSCLC) and solid tumors.

Abstract

e13124 Background: Patients (pts) with advanced NSCLC and solid tumors have a poor prognosis and novel approaches to improve targeting and cytotoxicity directed at these cancers are needed. Anti-CD3 activated T cells (ATC) can be expanded and armed with anti-CD3 x anti-EGFR bispecific antibody (EGFRBi). Methods: In a phase I trial using ATC armed with EGFRBi, 6 pts (NSCLC = 5 pts, pancreatic cancer =1 pt) were treated with 8 infusions (twice/week) for 4 weeks with 5, 10 billion armed ATC/dose to determine the maximum tolerated dose (3 pts each). T cells from leukopheresis were activated and expanded with anti-CD3/IL-2 for 14 days, harvested, armed with EGFRBi and cryopreserved. IL-2 (3 x 105 IU/m2/daily) and GM-CSF (250 µg/m2 twice/week) was given beginning 3 days prior to the 1st infusion and ending++ 3, performance status (PS 0= 2 pts, PS 1= 4 pts). Results: Restaging scans revealed stable disease in 2 pts and progression in 4 pts. One pt with NSCLC at each dose level had stable disease (23 mths, 11 mths). ATC infusions were well tolerated and noticeable toxicities included chills (grade 2= 1 pt, grade 3= 1 pt); headache (grade 1= 2 pts, grade 2= 2 pts), dizziness (grade 2= 1 pt), nausea (grade 1= 2 pts). Accrual continues for dose levels at 20, 40 billion armed ATC per dose. No major toxicities with IL-2 were observed; bone pain resulted in dose reductions for GM-CSF in 2 pts. Conclusions: Infusions of EGFRBi armed ATC can be safely accomplished in patients with advanced NSCLC and solid tumors; accrual continues.