A phase I study of the anti-idiotype vaccine racotumomab in neuroblastoma and

CACCIAVILLANO W(1), SAMPOR C(1), VENIER C(2), GABRI MR(3), DE DÁVILA MT(1),; GALLUZZO ML(1), GUTHMANN MD(4), FAINBOIM L(2), ALONSO DF(3), CHANTADA GL(1).

Pediatric Blood and Cancer

Wiley

Año: 2015

1545-5017

BACKGROUND: Pediatric neuroectodermal malignancies express N-glycolylatedgangliosides including N-glycolyl GM3 (NeuGcGM3) as targets for immunotherapy.PROCEDURE: We evaluated the toxicity and maximum tolerated dose and immunologicalresponse of racotumomab, an anti-idiotype vaccine targeting NeuGcGM3 through aPhase I study enrolling children with relapsed or resistant tumors expressingNeuGcGM3.MATERIALS AND METHODS: Drug dose was escalated to three levels (0.15-0.25-0.4 mg)of racotumomab administered intradermally. Each drug level included threepatients receiving a total of three doses, every 14 days. A confirmation cohortwas added to the highest dose level. Antibody response was assessed upon studyentry and at 4-week intervals for at least three immunological determinations foreach patient.RESULTS: Fourteen patients were enrolled (10 with neuroblastoma, one withretinoblastoma, one with Wilms' tumor, and two with brainstem glioma). Threepatients completed the three drug levels and three were enrolled in theconfirmation cohort. One patient died of tumor progression before completing the three applications. Racotumomab was well tolerated. The only side effect observedwas grade 1-2 toxicity at the injection site. Racotumomab elicited an IgM and/or IgG antibody response directed against NGcGM3 in nine patients and IgM againstracotumomab in 11 of 13 evaluable patients. The maximum tolerated dose was notreached and no dose-limiting toxicity was seen.CONCLUSIONS: Racotumomab vaccination has a favorable toxicity profile up to adose of 0.4 mg, and most patients elicited an immune response. Its activity asimmunotherapy for neuroectodermal malignancies will be tested in further clinicaltrials.