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.
In a 39-patient, open-label, single-arm phase 2 study of high-risk neuroblastoma, racotumomab induced anti-mouse and NeuGc-directed immune responses, including ADCC in a minority of patients, with no serious treatment-related adverse events and an exploratory association between IgM response and progression-free survival.
Open original publication →What the AI sees
In a 39-patient, open-label, single-arm phase 2 study of high-risk neuroblastoma, racotumomab induced anti-mouse and NeuGc-directed immune responses, including ADCC in a minority of patients, with no serious treatment-related adverse events and an exploratory association between IgM response and progression-free survival.
Research significance
The study provides evidence that racotumomab can elicit NeuGc glycoconjugate-directed antibodies and occasional ADCC in children with high-risk neuroblastoma; it supports, but does not establish, the hypothesis that vaccine-induced immunity against tumor-associated NeuGcGM3 could help control residual disease, particularly in immunologic responders.
Source 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.