A PHASE I STUDY OF RACOTUMOMAB IN NEUROBLASTOMA AND OTHER REFRACTORY MALIGNANCIES

WALTER CACCIAVILLANO, CLAUDIA SAMPOR, MARCELO GUTHMANN, MARIANO GABRI, EDUARDO LAGOMARSINO, MARÍA TG DE DÁVILA, GRACIELA GALAR, RODOLFO VERNA, LEONARDO FAINBOIM, DANIEL ALONSO, GUILLERMO CHANTADA.

Congreso; 2014 SIOP Annual Meeting; 2014

SIOP (Soicedad Internacional de Oncologia Pediatrica)

PURPOSE: Since we previously reported the expression of the ganglioside N-glycolyl GM3 (NGcGM3) in neuroblastoma and other neuroectodermic tumors, we aimed to evaluate the immunological response, toxicity and maximum tolerated dose of the anti-idiotype vaccine targeting N-glycolylated gangliosides including NGcGM3 (racotumomab, formerly known 1E10), as a candidate for immunotherapy. MATERIAL AND METHODS: A Phase I study enrolling children with relapsed or resistant neuroblastoma and other neuroectodermic tumors was carried out. Dose was escalated into 3 levels (0.15 ? 0.25 ? 0.4 mg) of racotumomab administered intradermally. Each drug level included 3 patients receiving racotumomab for a total of 3 doses, every 14 days; with clinical and laboratory evaluations at 30 and 60 days after the last dose was administered. A confirmation cohort of 3 additional patients was added to the higher dose level. Antibody response was assessed upon study entry and at 4-week intervals. RESULTS: 14 patients were enrolled (10 with neuroblastoma, 1 with retinoblastoma, 1 with Wilms tumor and 2 with brainstem tumor). 3 patients were included in each dose-level and 4 in the confirmation cohort. One patient died of tumor progression before completing the 3 applications. The remaining patients completed the applications scheduled. Racotumomab was well tolerated. The most common local side effects included grade 1 erythema, induration, and local mild pain at the injection site. Racotumomab elicited an antibody IgM and/or IgG response directed to NGcGM3 in a booster- and dose-dependent manner in 9 patients and antibodies against racotumomab in 11 patients. The maximum tolerated dose was not reached and no dose-limiting toxicity was seen, so the upper dose level of 0.4 mg will be considered for further clinical trials. No antitumor activity was evident in any enrolled patient. CONCLUSIONS: Racotumomab vaccination showed a favorable toxicity profile up to a dose of 0.4 mg, and most patients elicited an immune response. Its activity as immunotherapy for neuroblastoma will be tested in further clinical trials.