S-4 / Cellectis - LARVOL DELTA

Pharmacodynamic characterization of PRS-344/S095012, a PD-L1x4-1BB antibody-Anticalin fusion protein (Mabcalin), in a dose escalation study in patients with advanced solid tumors (AACR 2025) - P1/2 | "A cohort of 12 patients at the 36mg dose level was pre-treated with Obinutuzumab (OBI) to mitigate anti-drug antibody (ADAs) formation. Plasma and PBMCs were collected pre-dose (Cycle 1 Day 1), and on-treatment (during cycle 1) to measure cytokine levels, Soluble 4-1BB (s4-1BB) as a surrogate for target engagement, and immune cell activation by flow cytometry... S095012 elicited a robust, dose-dependent enhancement of immune cell activation, which was further amplified by OBI pre-treatment, increasing the incidence of irAEs. A target with more specific tumor expression than PD-L1 might be better suited for selective 4-1BB agonism to minimize immune toxicities related to systemic immune cell activation."

Clinical • IO biomarker • Metastases • PK/PD data • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL10 • TNFA