LAG-3 Inhibitor's Role in Cancer Immunotherapy

LAG-3 (Lymphocyte Activation Gene-3) has emerged as a pivotal target in cancer immunotherapy, opening new avenues in the effort to leverage the immune system to fight cancer. Discovered in 1990, LAG-3 is a crucial cell surface molecule involved in regulating T cell function and has been recognized as a key immune checkpoint. In March 2022, Bristol Myers Squibb received approval for Opdualag™ (a combination of nivolumab and relatlimab-rmbw), the world's first LAG-3 inhibitor therapy. This treatment is designed for adult and pediatric patients aged 12 and older with unresectable or metastatic melanoma. Neeraj Chawla, Research Head at Kuick Research, predicts that the global market for LAG-3 drugs will surpass $3 billion by 2029, with more drugs expected to enter the market by the end of the decade.

From a clinical perspective, LAG-3 has gained considerable attention as a potential target for cancer immunotherapy. It has been found to work in synergy with other immune checkpoints like PD-1 and CTLA-4, enhancing tumor immune evasion. This has led to the development of LAG-3 inhibitors, such as monoclonal antibodies that block LAG-3 and restore T cell function. Many of these inhibitors are currently in clinical trials, both as standalone treatments and in combination with other immune checkpoint inhibitors. Preliminary results from these trials have shown promising safety and efficacy across various cancer types, including melanoma, non-small cell lung cancer, and renal cell carcinoma.

Commercially, the market for LAG-3 inhibitors is set for significant growth. The success of approved therapies has led to a doubling of sales, surpassing half a billion dollars in 2023. This success highlights the pharmaceutical sector's potential for future growth. Additionally, combination therapies involving LAG-3 inhibitors present significant commercial opportunities, potentially offering better clinical outcomes compared to monotherapies.

Numerous clinical trials are ongoing to further understand the role of LAG-3 in cancer treatment. For example, ABL Bio, a South Korean biotech company, has initiated a first-in-human phase 1 study of ABL501. This open-label, multicenter trial aims to evaluate the safety, tolerability, maximum tolerated dose, recommended phase 2 dose, pharmacokinetics, immunogenicity, preliminary anti-tumor activity, and pharmacodynamic effects of ABL501 in patients with progressive, locally advanced (unresectable) or metastatic solid tumors. The study began in October 2021 and is expected to be completed by December 2024.

In addition to clinical trials, several preclinical candidates targeting LAG-3 have been developed. Y Biologics, for instance, has created a novel mono-specific LAG-3 therapy, YBL-011, which is currently in the preclinical stage for treating solid tumors. The global interest in LAG-3 therapies is also influencing the immunotherapy market, as multinational pharmaceutical companies seek collaborations with local firms to leverage advanced research capabilities. These international collaborations not only enhance technological exchange but also open new investment and growth opportunities.

In June 2024, Immutep, an Australian company, announced a clinical trial collaboration and supply agreement with Merck. This partnership aims to evaluate the combination of eftilagimod alfa (efti) with the anti-PD-1 therapy Keytruda (pembrolizumab) and chemotherapy for the first-line treatment of metastatic non-small cell lung cancer in a pivotal Phase III trial.

In summary, targeting LAG-3 in cancer therapy offers a promising approach to enhancing anti-tumor immune responses and overcoming resistance to existing immunotherapies. Ongoing clinical trials and substantial commercial interest highlight the potential impact of LAG-3 inhibitors in the evolving landscape of cancer treatment. However, continued research and clinical validation are essential to fully realize their therapeutic potential.