Preliminary safety, antitumor activity, and pharmacodynamics of intratumoral ABO2011 (IL-12 mRNA) in patients with advanced solid tumors.

• DOI: 10.1200/jco.2024.42.16_suppl.e14583
• Publication Date: 2024-06-04T19:40:32Z
• Authors: Ning Li; Ning Li; Yong Wang; Ningyi Cui; Xin Wang; Yu Tang; Yuting Chu; Qingwei Meng; Rui Lin; Yan Wu; Bo Ying
• Keywords: Pharmacodynamics; Solid tumor

e14583 Background: Interleukin (IL)-12 is a potent immunomodulatory cytokine demonstrating robust antitumor activity in multiple preclinical studies and immune-stimulating potential humans. However, systemic delivery of IL-12 can result life-threatening toxicity therefore has shown limited efficacy at doses that be safely administered. ABO2011 human mRNA encapsulated lipid nanoparticle been developed to more effective less toxic through the use novel technology intratumoral injection. Methods: This phase I trial enrolled adults with advanced solid tumors who failed available standard treatments (NCT05392699). The was designed primarily evaluate safety single-dose cohorts multiple-dose using “3+3” dose escalation approach. Patients (pts) would receive either single dose, QW 3 overall, every weeks (Q3W) or followed by Q3W. Results: As 09 December 2023, total 20 pts were received least one 4 μg for times, 12 times Q3W, 24 Q3W 48 Seventeen (85%) experienced treatment-related adverse events (TRAEs), all grade 1 2, including pyrexia (35%), pain (25%), gamma-glutamyl transferase increased (25%). There no dose-limiting toxicities SAEs reported TRAEs leading treatment discontinuation. Of 17 evaluable per RECISIT v1.1, 5 maintained stable disease, progression free survivals achieved 6.0 months, 5.6 months 4.1 colorectal cancer (6 th line), non-small cell lung (5 line) pancreatic (4 respectively. Peripheral blood IFN-γ levels peaked hours after dosing, respectively, indicating expression subsequent induction administration. Dose-dependent elevation CXCL9, CXCL10, CXCL11 peripheral observed, consistent activation downstream pathway IFN-γ. CD8 T cells infiltration PD-L1 tumor microenvironment (TME) day 7, further RNA sequencing analysis revealed increase activated antigen processing presentation study treatment, suggesting regulation TME supporting combination PD-1(L1) inhibitor. Conclusions: Intratumoral safe well-tolerated tumors. pharmacodynamic changes as expected. Promising preliminary activities agent profiles support investigation immune checkpoint Clinical information: NCT05392699 .