Safety and Feasibility of AloCelyvir Combined with Autologous IL‑7/15/21‑Expanded TILs in Children/Young Adults with High‑Risk Relapsed/Refractory Neuroblastoma

The primary objective is to determine the safety and tolerability of the sequential administration of AloCelyvir and autologous tumor‑infiltrating lymphocytes in patients with high‑risk relapsed/refractory neuroblastoma, providing essential data for risk assessment in this vulnerable population. Secondary objectives include:

• Evaluation of pharmacodynamic effects of the combined cellular therapy.
• Characterization of the safety profile through incidence and severity grading of adverse events according to NCI CTCAE version 5.0.
• Collection of preliminary efficacy endpoints, specifically objective response rate, clinical benefit rate, progression‑free survival, and overall survival.

The trial enrolled pediatric patients diagnosed with high‑risk relapsed/refractory neuroblastoma for whom no curative therapy is available. Eligible participants were aged from 1 month to 21 years, of either sex, and required a minimum weight of 3 kg. Inclusion required measurable disease by imaging or bone‑marrow assessment, ability to undergo an excisional biopsy for tumor‑infiltrating lymphocyte collection, life expectancy greater than 14 weeks, and adequate organ function. Female participants of childbearing potential needed a recent negative pregnancy test and adherence to contraceptive requirements; sexually active males were required to use condoms for the study duration and one year thereafter. All subjects were considered vulnerable due to their age. The sponsor did not provide the total number of participants enrolled.

The trial is a phase 1, single‑arm, open‑label feasibility study evaluating sequential administration of AloCelyvir followed by autologous tumor‑infiltrating T lymphocytes expanded with interleukin‑7, interleukin‑15 and interleukin‑21 in children and young adults with high‑risk relapsed/refractory neuroblastoma. After written informed consent, participants undergo a screening visit to confirm eligibility, obtain baseline imaging, laboratory assessments, and an excisional tumor biopsy for TIL manufacturing. Eligible subjects receive an intravenous infusion of AloCelyvir, followed 7–14 days later by an intravenous bolus of the expanded TIL product, each administered in a dedicated treatment visit with safety monitoring. Follow‑up visits are scheduled at weeks 2, 4, 8, 12 and then every 3 months up to 12 months, comprising physical examination, vital signs, laboratory tests, and imaging per International Neuroblastoma Response Criteria to assess response and adverse events. Participant involvement extends from screening through the end‑of‑study visit at month 12, encompassing approximately 14‑16 weeks of active treatment plus 12 months of follow‑up. Early termination may occur if a dose‑limiting toxicity is identified, if disease progression precludes further therapy, if the patient withdraws consent, or if organ function falls below protocol‑defined thresholds.

The investigational product identified as autologous tumor-infiltrating T lymphocytes, ex vivo expanded with interleukin-7, interleukin-15 and interleukin-21 is supplied as a cell suspension for injection and is administered by intravenous bolus injection/IV infusion. The preparation is derived from the patient’s own tumor tissue, expanded ex vivo in the presence of interleukin‑7, interleukin‑15 and interleukin‑21, and delivered as a single or multiple intravenous infusion according to the study‑specified schedule.

The second investigational product, allogeneic bone marrow‑derived mesenchymal stem cells transduced with icovir‑5, ex vivo expanded (commercially designated AloCelyvir), is also provided as a cell suspension for injection and administered by intravenous bolus injection/IV infusion. The allogeneic mesenchymal stem cells are genetically modified with the oncolytic virus icovir‑5, expanded under GMP conditions, and infused intravenously in accordance with the protocol‑defined dosing timeline.

Both cellular therapies are given sequentially, with AloCelyvir administered first followed by the autologous TIL product. Administration occurs in a clinical setting under close observation. Compliance monitoring includes documentation of infusion start and end times, cell viable counts, and any infusion‑related adverse events, as recorded in the trial case report forms.

Efficacy will be evaluated using objective tumor response assessments, including response rate (complete and partial responses) and clinical benefit rate (complete response, partial response, minor response, and stable disease). Additional efficacy measures comprise progression‑free survival and overall survival. These parameters will be derived from serial imaging and clinical evaluations performed according to the trial schedule, and data will be analyzed with appropriate statistical methods to estimate response proportions and survival outcomes.