To determine the MTD of Seneca Valley Virus (NTX‐010) in children with relapsed/refractory solid tumors. Patients (≥3–≤21 years) with neuroblastoma, rhabdomyosarcoma, or rare tumors with neuroendocrine features were eligible.

Part A (single dose of NTX‐010) enrolled 13 patients at three dose levels (1 × 10⁹ viral particles (vp)/kg [n = 6], 1 × 10¹⁰ vp/kg [n = 3], 1 × 10¹¹ vp/kg [n = 4]). Diagnoses included neuroblastoma (n = 9), rhabdomyosarcoma (n = 2), carcinoid tumor (n = 1), and adrenocorticocarcinoma (n = 1). Part B added cyclophosphamide (CTX) (oral CTX (25 mg/m²/day) days 1–14 and IV CTX (750 mg/m²) days 8 and 29) to two doses of NTX‐010 (1 × 10¹¹ vp/kg, days 8 and 29). Nine patients enrolled to Part B. Diagnoses included neuroblastoma (n = 3), rhabdomyosarcoma (n = 1), Wilms tumor (n = 3), and adrenocorticocarcinoma (n = 2).

Twelve patients on Part A were evaluable for toxicity. There was a single DLT (grade 3 pain) at dose level 1. Additional grade ≥3 related adverse events (AEs) included leukopenia (n = 1), neutropenia (n = 3), lymphopenia (n = 3), and tumor pain (n = 1). No DLTs occurred on part B. Other grade ≥3 related AEs on Part B included: Leukopenia (n = 3), nausea (n = 1), emesis (n = 1), anemia (n = 1), neutropenia (n = 4), platelets (n = 1), alanine aminotransferase (n = 1), and lymphopenia (n = 2). All patients cleared NTX‐010 from blood and stool by 3 weeks with 17/18 patients developing neutralizing antibodies.

NTX‐010 is feasible and tolerable at the dose levels tested in pediatric patients with relapsed/refractory solid tumors either alone or in combination with cyclophosphamide. However, despite the addition of cyclophosphamide, neutralizing antibodies appeared to limit applicability. Pediatr Blood Cancer 2015;62:743–750. © 2014 Wiley Periodicals, Inc.