Immune checkpoint blockade is a new therapeutic paradigm that has led to durable anti-tumor effects in patients with metastatic melanoma, non-small cell lung cancer, and other tumor types. Despite this remarkable success, determining which patients will respond to cancer immunotherapy remains an elusive goal. Combining cancer exome sequencing with a newly developed, state-of-the-art bioinformatic platform, Drs. Jedd Wolchok and Timothy Chan have identified the genetic basis for clinical response to immune checkpoint inhibition. They have developed a neoepitope signature that predicts clinical benefit from the anti-CTLA4 drug Yervoy (ipilimumab) for melanoma. Additionally, they have identified a distinct molecular signature that correlates with clinical benefit from the anti-PD1 drug Keytruda (pembrolizumab) for non-small cell lung cancer. These findings provide a strong rationale for examining the tumor’s genetic landscape in patients for whom immune checkpoint inhibitors are being considered for therapy.
- Increase efficacy of treatment by identifying patients who might benefit from checkpoint inhibitors
- Optimize clinical trial design by stratifying patients, thereby reducing clinical trial costs
- Expand the market by identifying patients with cancers not currently treated with checkpoint inhibitors
- Identify the appropriate checkpoint inhibitor for therapy based on patient’s mutational profile
The market for immune checkpoint inhibitors is predicted to grow from $1 billion in 2013 to over $7 billion in 2020. Revenue from sales of Yervoy was $1.3 billion in 2014. Currently approved drugs in this class cost between $120,000 and $150,000 per patient, but only a fraction of these patients experience durable clinical responses. Identifying those who will benefit from immune checkpoint inhibitors will broaden the pool of potential patients and result in significant cost savings for patients and payors.
- Snyder A et al. (2014) Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma. The New England Journal of Medicine 371: 2189-2199 (PubMed link)
- Rizvi NA et al. (2015) Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science 348: 124-128 (PubMed link)
PCT and Provisional applications pending
- Jedd D. Wolchok, MD, PhD, Chief, Melanoma and Immunotherapeutics Service; Lloyd J. Old Chair for Clinical Investigation, Memorial Sloan Kettering
- Timothy A. Chan, MD, PhD, Laboratory Head, Human Oncology & Pathogenesis Program, Memorial Hospital Research Laboratories, Memorial Sloan Kettering