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TransCon IL-2 β/γ + paclitaxel is an investigational combination regimen consisting of onvapegleukin alfa (TransCon IL-2 β/γ), a long-acting prodrug of a receptor-biased interleukin-2 (IL-2) variant, and the microtubule-stabilizing chemotherapeutic agent paclitaxel. Developed by Ascendis Pharma, onvapegleukin alfa is designed using their proprietary TransCon (transient conjugation) technology, where a modified IL-2 cytokine is transiently linked to a polyethylene glycol (PEG) carrier. This modification blocks binding to the high-affinity IL-2 receptor alpha (IL-2Rα) subunit, thereby selectively activating the intermediate-affinity beta/gamma (IL-2Rβ/γ) receptor. This selectivity promotes the expansion of cytotoxic CD8+ T cells and natural killer (NK) cells while avoiding the activation of immunosuppressive regulatory T cells (Tregs) and minimizing toxicities like vascular leak syndrome. Paclitaxel works by binding to tubulin, inhibiting microtubule disassembly, and arresting cell division. The combination was evaluated in the Phase 1/2 IL-Believe trial for patients with platinum-resistant ovarian cancer (PROC) and other advanced solid tumors. In May 2026, Ascendis Pharma announced its decision to discontinue internal development of onvapegleukin alfa in oncology to focus on its rare endocrinology portfolio.
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