First-In-Human Trial of Encapsulated Cells Constitutively Expressing Localized IL2 in Patients with High-Grade Serous Ovarian Carcinoma.

PURPOSE: Platinum-resistant high-grade serous ovarian carcinomas (HGSOC) are associated with poor therapeutic outcomes. Although HGSOC frequently metastasizes to the intraperitoneal (IP) cavity, the success of IP cytokine therapies, such as IL2, has been hampered by local toxicity and administration difficulties. AVB-001 is a novel IL2 delivery system consisting of encapsulated, allogeneic cells engineered for constitutive human IL2 (hIL2) 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 by IP laparoscopy, enabling hIL2 doses from 0.6 to 3.6 μg hIL2/kg/day. Safety was evaluated using NCI Common Terminology Criteria for Adverse Events v5.0. Efficacy was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immunotherapy RECIST criteria.

RESULTS

The trial enrolled 14 patients across four dose levels. Three (21.4%) patients experienced grade 3 treatment-related adverse events (TRAE); no grade 4 to 5 TRAEs were reported. There was one dose-limiting toxicity. There was one unconfirmed partial response but no confirmed responses (overall response rate 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 IL2, peaking at 1 day after implantation. Immunologic 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.