iLeukon Secures FDA Clearance for Phase II mRNA Cancer Trial

iLeukon Receives FDA Clearance for ILKN421H

On November 4, 2025, iLeukon Therapeutics, a San Diego-based biotechnology firm, announced that the U.S. Food and Drug Administration (FDA) has granted clearance for its Investigational New Drug (IND) application. This approval permits the company to initiate a Phase II clinical trial of ILKN421H, an innovative mRNA-based therapy designed for patients suffering from advanced non-small cell lung cancer (NSCLC). The Phase II study will assess the efficacy of ILKN421H in combination with pembrolizumab, a checkpoint inhibitor commonly used in cancer treatment.

What is ILKN421H?

ILKN421H is a unique therapy formulated using lipid nanoparticles (LNP) and encodes a non-alpha HSA–IL-2v fusion protein. This mRNA therapy is administered through intravenous injection every three weeks, achieving targeted expression in lymphoid organs. Notably, ILKN421H has demonstrated an extended half-life of approximately 20 hours, allowing for sustained activation of immune responses. The non-alpha design facilitates the selective expansion of crucial immune cells, namely CD8 T and NK (natural killer) cells, which are vital in combating tumors.

In initial studies, ILKN421H has shown the ability to increase the number of these immune cells by as much as five-fold for CD8 T cells and twenty-five-fold for NK cells. This expands the therapeutic potential for cancer patients who often face limitations with conventional treatments.

Safety and Efficacy of ILKN421H

The First-in-Human Phase I trial (NCT05978102) evaluated ILKN421H both as a standalone treatment and in conjunction with pembrolizumab. Results indicated a favorable safety profile, with no instances of significant side effects such as vascular-leak syndrome or hypotension. This trial enrolled 45 participants with advanced solid tumors, and the combination therapy reported an impressive objective response rate (ORR) of 80% among 20 patients with NSCLC, regardless of their PD-L1 expression levels.

Moreover, the therapy exhibited promising progression-free survival rates, although the exact duration has yet to be fully established, with projections indicating it could exceed 12 months. The findings from this Phase I study are set to be presented at the upcoming Society for Immunotherapy of Cancer (SITC) Annual Meeting on November 8, 2025.

Comments from Leadership

Haining Huang, the CEO of iLeukon Therapeutics, expressed enthusiasm regarding the clearance, underscoring ILKN421H's role as a potential breakthrough in immune-oncology. He stated, "Next-generation IL-2 agents have been a major focus of the immuno-oncology field for the past decade." Huang emphasized that ILKN421H’s ability to enhance the activity of CD8 T cells and NK cells safety marks it as a significant advancement in cancer treatment.

The company believes that combining ILKN421H with checkpoint inhibitors like pembrolizumab could lead to enhanced therapeutic outcomes, addressing a critical gap in NSCLC and potentially other cancer indications in the future.

Future Directions

Having secured FDA clearance for the Phase II trial, iLeukon Therapeutics is poised to take significant steps towards meeting urgent medical needs in cancer treatment. With ongoing research, the company aims to enhance the efficacy of its therapies further and explore applications in conjunction with additional modalities such as TIL (tumor-infiltrating lymphocytes) and in vivo CAR-T (chimeric antigen receptor T-cell therapy) approaches.

As the landscape of cancer treatment continues to evolve, iLeukon strives to be at the forefront, innovating and pushing the boundaries of current treatment paradigms to offer improved outcomes for patients battling formidable challenges posed by advanced cancers.