On November 4, 2025 iLeukon Therapeutics, Inc., a San Diego-based clinical-stage biotechnology company developing next-generation mRNA-based immunotherapies, reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application and a phase II protocol evaluating ILKN421H in combination with pembrolizumab for first line and post-IO treatment of patients with advanced NSCLC.
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ILKN421H is a novel LNP-formulated mRNA therapy encoding a non-alpha HSA–IL-2v fusion protein for the treatment of cancer. Administered intravenously every three weeks, ILKN421H achieves efficient and preferential mRNA expression in lymphoid organs with an extended half-life of IL-2v approximately 20 hours. Its non-alpha IL-2v design selectively expands stem-like CD8 T and NK cells, while the mRNA platform overcomes cytokine-sink limitations seen with protein-based IL-2 therapies—offering the potential for greater efficacy with reduced systemic toxicity.
In a first-in-human, open-label Phase I study (NCT05978102), ILKN421H demonstrated antitumor activity and a favorable safety profile, with no cases of vascular-leak syndrome or hypotension. In this trial evaluating ILKN421H as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors, ILKN421H was well tolerated, with no dose-limiting toxicities and no maximum tolerated dose reached among the 45 enrolled patients. Combination therapy with pembrolizumab, in first-line NSCLC, achieved a confirmed objective response rate (ORR) of 80% (n=16/20) regardless of PD-L1 expression, with median progression-free survival (PFS) not yet reached and projected to exceed 12 months. The summary of this Phase I study was selected as an oral presentation at the upcoming SITC (Free SITC Whitepaper) Annual Meeting, and the results will be presented on November 8, 2025.
"Next-generation IL-2 agents have been a major focus of the immuno-oncology field for the past decade," said Haining Huang, Chief Executive Officer of iLeukon Therapeutics. "ILKN421H expands cytotoxic lymphocytes—CD8 T cells and NK cells—by up to five- and twenty-five-folds respectively, the first IL-2 based treatment that achieved this level of immune promotion safely. We believe ILKN421H can enhance the efficacy of checkpoint inhibitors, such as pembrolizumab, and may also support future modalities including TIL and in vivo CAR-T therapies. With FDA clearance to proceed to phase II, we look forward to advancing ILKN421H globally to meet the significant unmet needs and to improve the outcomes for patients with NSCLC and potentially other types of cancers in the future."
(Press release, iLeukon Therapeutics, NOV 4, 2025, View Source [SID1234659397])