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iLeukon Therapeutics Presents Phase I Data for ILKN421H at SITC 2025

On November 11, 2025, iLeukon Therapeutics, a biotechnology firm based in San Diego, shared groundbreaking findings from their ongoing first-in-human Phase I clinical trial of ILKN421H. This phase of the trial was showcased during a Late-Breaking Clinical Oral Session at the esteemed Society for Immunotherapy of Cancer (SITC) Annual Meeting held in National Harbor, Maryland.

What is ILKN421H?

ILKN421H is an innovative mRNA-based therapeutic designed to treat advanced solid tumors. The agent utilizes a lipid-nanoparticle (LNP) formulation that encodes a non-alpha human serum albumin-interleukin 2 variant (IL-2v). This study involves evaluating the therapeutic as a standalone treatment and in conjunction with pembrolizumab for patients suffering from various types of advanced solid tumors, with a primary focus on newcomers battling non-small cell lung cancer (NSCLC).

Key Findings from the Phase I Trial

The data presented revealed that ILKN421H is engineered for potency and offers significant pharmacological advantages ensuring immune activation while maintaining a favorable safety profile. Researchers noted the following benefits:

1. Stem-like CD8+ T Cell Amplification: ILKN421H promotes the selective expansion of PD1- stem-like CD8⁺ T cells, which are essential for self-renewal and long-lasting immune responses against tumors.

2. Targeted Distribution: The mRNA delivered by ILKN421H predominantly accumulates in lymphoid tissues (such as spleen and lymph nodes) while minimizing systemic exposure. This biodistribution enhances immune activity while limiting unintended effects on other organs.

3. Cytokine-sink Bypassing: Unlike traditional protein-based IL-2 therapies, ILKN421H's sustained mRNA delivery circumvents rapid degradation, promoting effective CD8+ T and NK cell proliferation. Remarkably, this is achieved with only one-hundredth the systemic exposure of IL-2v seen in conventional protein therapies.

4. Safety and Tolerability: Across a cohort of 45 patients with advanced solid tumors, ILKN421H was well tolerated. Notably, there were no occurrences of dose-limiting toxicities (DLTs) or serious adverse events in more than one patient. While there were some Grade 3 adverse events observed, including anemia and fever, they were well within acceptable ranges.

Clinical Efficacy

In terms of effectiveness, the trial included 20 patients suffering from Stage I non-small cell lung cancer (NSCLC). The combination of ILKN421H with pembrolizumab demonstrated an impressive objective response rate (ORR) of 80%, with detailed analysis revealing an ORR of 87% in PD-L1-positive patients and 60% in their PD-L1-negative counterparts. Median progression-free survival is anticipated to surpass 12 months.

In the post-immunotherapy segment of NSCLC patients, the combination exhibited an ORR of 33.3%, showcasing both a partial response and durable stable disease among participants.

Next Steps: Phase II Development

Following these promising results, the FDA has granted iLeukon clearance to move forward with a Phase II study designed to further explore ILKN421H in combination with pembrolizumab for ongoing treatment of both first-line and post-immunotherapy patients.

Dr. Haining Huang, CEO of iLeukon Therapeutics, emphasized the significance of these findings, stating, "The results not only validate the novel design of ILKN421H but also underscore its potential to offer substantial clinical benefits for cancer patients. We are excited to progress this pivotal program into advanced development phases."

Conclusion

The insights gained from these Phase I trial results signal the evolution of IL-2 therapy by integrating mRNA technology with a focus on selective immune activation. As iLeukon Therapeutics embarks on its Phase II trials, the potential for ILKN421H to reshape the landscape of cancer treatment continues to capture global attention.