Phase I study of the humanized anti-epidermal growth factor receptor (EGFR) antibody EMD 72000 (matuzumab) in combination with cisplatin, 5-fluorouracil and leucovorin (PFL) in patients (pts) with advanced esophago-gastric (EG) adenocarcinoma

Abstract

3156 Background: EG cancer is diagnosed in more than 60% of patients (pts) in a locally advanced or metastatic stage. In this situation treatment options are limited; therefore exploration of a new therapeutic regimen is warranted. EGFR is expressed in a high proportion of gastric cancers associated with poor prognosis. Matuzumab, a humanized monoclonal anti-EGFR IgG1 antibody, inhibits ligand-mediated receptor signalling and has demonstrated antitumor activity in solid tumors. In a phase I study we evaluated the safety, tolerability, and pharmacokinetics of matuzumab in combination with standard chemotherapy in pts with advanced EG adenocarcinoma. Methods: Weekly doses of matuzumab (400 mg or 800 mg) were administered in addition to PFL (cisplatin [50 mg/m2] days 1, 15, 29, and leucovorin [500 mg/m2] and 5-fluorouracil [2000 mg/m2] days 1, 8, 15, 22, 29, 36) on a 7-week cycle up to a maximum of 3 cycles. Tumor response was assessed by endoscopy and CT/MRI in the last week of each cycle. Blood samples were drawn weekly for pharmacokinetic analysis during the first cycle. Results: 9/10 (90%) screened pts were EGFR-positive. 5 male/4 female pts with a median age of 49 years (range 41–64), median performance status 100, and 1 pt stage III, 8 pts stage IV received either 400 mg (n = 7) or 800 mg (n = 2) matuzumab weekly plus PFL. No drug-related serious adverse events occurred. Desquamation of the skin (grade 3) in 1 pt (800 mg) was the only grade 3/4 drug-related event. Skin toxicities grade 1/2 were observed in 6/7 (85%) and 1/2 (50%) pts in the 400-mg and 800-mg groups, respectively. Best overall response of 8 evaluable pts: 4 PR, 1 SD, 1 PD with 400 mg and 2 PR with 800 mg. PK data will be presented. Conclusions: Preliminary results indicate that the combination of weekly matuzumab and PFL might be well tolerated in the first-line treatment of advanced EG adenocarcinoma. Further data will need to be generated to confirm definite antitumor activity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck KGaA Merck KGaA Darmstadt, Ortho-Biotech Ortho-Biotech