First-In-Human Trial of Encapsulated Cells Constitutively Expressing Localized IL-2 in Patients with High-Grade Serous Ovarian Carcinoma

PURPOSE: Platinum-resistant high-grade serous ovarian carcinomas (HGSOC) are associated with poor therapeutic outcomes. While HGSOC frequently metastasizes to the intraperitoneal (IP) cavity, the success of IP cytokine therapies, such as IL-2, has been hampered by local toxicity and administration difficulties. AVB-001 is a novel IL-2 delivery system consisting of encapsulated, allogeneic cells engineered for constitutive human IL-2 expression. PATIENTS AND METHODS: This is a phase I dose-escalation trial of AVB-001 for the treatment of HGSOC (NCT05538624). A single dose of AVB-001 was administered IP laparoscopically, enabling hIL-2 doses from 0.6 to 3.6 μg hIL-2/kg/day. Safety was evaluated using NCI CTCAE v5.0. Efficacy was assessed via RECIST v1.1 and iRECIST criteria. RESULTS: The trial enrolled 14 patients across four dose levels. Three patients (21.4%) experienced grade 3 treatment-related adverse events (TRAEs); no grade 4-5 TRAEs were reported. There was one DLT. There was one unconfirmed partial response, but no confirmed responses (ORR 0%). Stable disease was observed in seven patients, with a median duration of 2.57 months (range 2.03-4.23). The clinical benefit rate was 14.3% (n=2). Pharmacokinetics demonstrated dose-dependent increases in serum IL-2, peaking at 1 day post-implantation. Immunological analyses revealed sustained CD8+ and CD4+ T-cell proliferation without corresponding proliferation in regulatory T cells. Dose-dependent CTLA-4 receptor upregulation was observed on CD8+ and CD4+ T cells, whereas PD-1 and TIM-3, remained unchanged. CONCLUSIONS: In patients with HGSOC, AVB-001 is safe and effectively activates cytotoxic T cells, supporting further investigation of this locoregional immunotherapy.