First-In-Human Trial of Encapsulated Cell-Based Protein Producers for Localized IL-2 in Patients with High-Grade Serous Ovarian Carcinoma
Clark, H. D.; Aghlara-Fotovat, S.; Schladenhauffen, J.; Debonis, J.; Amador-Molina, J. C.; Nash, A.; Jain, M.; Newman, R.; Jansen, L.; Andreas, K.; Rangel, K.; Sims, T. T.; Fellman, B.; Ullman, C. D.; Yeku, O.; Bregar, A. J.; Blakely, A. M.; Mathews, C.; Igoshin, O. A.; Haymaker, C.; Oberholzer, J.; Rios, P.; Lopez, D.; Nasir, H.; Joshi, I.; Chakrabarti, R.; Veiseh, O.; Jazaeri, A. A.; Westin, S. N.
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BackgroundPlatinum-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. MethodsThis 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 g hIL-2/kg/day. Safety was evaluated using NCI CTCAE v5.0. Efficacy was assessed via RECIST v1.1 criteria. FindingsThe 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 unconfirmed partial response lasting 29 days (ORR 7.1%). Stable disease was observed in seven patients, with a median duration of 2.57 months (range 2.03-4.23). 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. ConclusionIn patients with HGSOC, AVB-001 is safe and effectively activates cytotoxic T cells, supporting further investigation of this locoregional immunotherapy. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/25339137v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@b201fdorg.highwire.dtl.DTLVardef@a0a82corg.highwire.dtl.DTLVardef@18106faorg.highwire.dtl.DTLVardef@1f14568_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG
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