Immune Response and Safety of Anti‐NeuGcGM3 Anti‐Idiotype Vaccine Racotumomab in Patients With High‐Risk Neuroblastoma: An Open‐Label, Single‐Arm, Multicenter Phase 2 Study in Argentina

ABSTRACT Background Racotumomab is a murine anti‐idiotype monoclonal antibody targeting N‐glycolylated (NeuGc) glycoconjugates like NeuGcGM3 ganglioside, expressed in nearly 85% of neuroblastoma tumors. Aims To report the immune response, safety, and clinical outcomes in subjects with high‐risk neuroblastoma (HR‐NB) treated with racotumomab in a Phase 2 study (NCT02998983). Methods Subjects were assigned to two strata. Stratum 1 included those in first or second very good partial remission (VGPR) or complete remission (CR) after first‐ or second‐line conventional treatments for HR‐NB. Stratum 2 included those in partial remission (PR) or stable disease (SD) after first‐ or second‐line treatment. Racotumomab was administered as five biweekly doses followed by 10 monthly doses (1 year total). Serum anti‐vaccine and anti‐NeuGc glycoconjugates antibody titers were quantified by enzyme‐linked immunosorbent assay, and antibody‐dependent cell‐mediated cytotoxicity (ADCC) was assessed using a luminescence‐based assay. Adverse events were graded per CTCAE v4.0. Results Thirty‐nine patients met eligibility criteria, with 35 (89.7%) having Stage M disease at diagnosis. Twelve (30.8%) had N‐myc amplification, 27 (69.2%) prior ASCT, and two (5.1%) prior anti‐GD2 immunotherapy. Twenty‐six were assigned to Stratum 1 (median age: 5.5 years) and 13 to Stratum 2 (median age: 6.3 years). Immune responses included human anti‐mouse antibodies in 37 (97%), NeuGc glycoconjugate‐specific IgM/IgG in 16 (42%), and ADCC in eight (21%) at 3 and/or 6 months. No serious treatment‐related adverse events occurred. In patients treated in VGPR/CR (Stratum 1), the 3‐year progression‐free survival was 0.48 (95% confidence interval CI: 0.28–0.66). Subjects with IgM responses had improved progression‐free survival ( p = 0.046). Conclusions Racotumomab elicited immune responses without serious related adverse events in HR‐NB patients.