iLeukon Receives FDA Clearance for Phase II Trial of mRNA-Based IL-2 Therapy ILKN421H in Advanced NSCLC
核心洞察
iLeukon Therapeutics (搜索) received FDA clearance for a Phase II trial evaluating ILKN421H (搜索), a novel mRNA-based IL-2 variant, in combination with pembrolizumab for advanced non-small cell lung cancer treatment.
The therapy demonstrated an 80% confirmed objective response rate in 20 first-line NSCLC patients regardless of PD-L1 (搜索) expression levels in Phase I trials.
ILKN421H (搜索) selectively expanded stem-like CD8 T cells up to 5-fold and NK cells up to 25-fold while maintaining a favorable safety profile with no vascular-leak syndrome or hypotension cases.
iLeukon Therapeutics (搜索) announced that the U.S. Food and Drug Administration has cleared its Investigational New Drug application for a Phase II trial evaluating ILKN421H (搜索) in combination with pembrolizumab for first-line and post-immunotherapy treatment of patients with advanced non-small cell lung cancer. The San Diego-based clinical-stage biotechnology company is developing next-generation mRNA-based immunotherapies targeting cancer treatment.
Novel mRNA-Based IL-2 Variant Shows Promise
ILKN421H (搜索) represents a novel lipid nanoparticle-formulated mRNA therapy encoding a non-alpha HSA–IL-2v fusion protein designed for cancer treatment. Administered intravenously every three weeks, the therapy achieves efficient and preferential mRNA expression in lymphoid organs with an extended half-life of IL-2v approximately 20 hours. The 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.
Impressive Phase I Results Drive Regulatory Advancement
In a first-in-human, open-label Phase I study (NCT05978102), ILKN421H (搜索) demonstrated significant antitumor activity and a favorable safety profile. The trial evaluated ILKN421H as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors, with 45 enrolled patients showing no dose-limiting toxicities and no maximum tolerated dose reached.
The combination therapy with pembrolizumab achieved a confirmed objective response rate of 80% (n=16/20) in first-line NSCLC patients regardless of PD-L1 (搜索) expression. Median progression-free survival has not yet been reached and is projected to exceed 12 months. Notably, no cases of vascular-leak syndrome or hypotension were observed during the trial.
Significant Immune Cell Expansion
ILKN421H (搜索) selectively expanded stem-like CD8 T cells up to 5-fold and NK cells up to 25-fold in patients with advanced solid tumors. According to Haining Huang, Chief Executive Officer of iLeukon Therapeutics (搜索), "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."
Future Clinical Development
The FDA-cleared Phase II trial will further evaluate ILKN421H (搜索) in combination with pembrolizumab for both first-line and post-immunotherapy treatment of NSCLC. Huang noted that the company believes ILKN421H can enhance the efficacy of checkpoint inhibitors and may also support future modalities including tumor-infiltrating lymphocyte and in vivo CAR-T therapies.
The summary of the Phase I study was selected as an oral presentation at the upcoming Society for Immunotherapy of Cancer Annual Meeting, with results scheduled for presentation on November 8, 2025. iLeukon Therapeutics (搜索), founded in 2020, develops first-in-class IL-2-based mRNA therapies for cancer immunotherapy, with a pipeline that includes ILKN421H (搜索) in combination with checkpoint inhibitors and in vivo CAR-T approaches for solid tumors and B-cell lymphomas.