Tomivosertib (also known as eFT508) is a novel, potent and highly selective oral small molecule inhibitor of mitogen-activated protein kinase interacting kinases 1 and 2, or collectively, MNK1/2. MNK1/2 play a crucial role in the development of many tumors, including by controlling in a coordinated manner the expression of multiple factors that attenuate an immune response.
The interaction between a patient’s tumor and immune system has been described as a cyclical process referred to as the cancer immunity cycle. Our studies have shown that tomivosertib acts on multiple points in the cancer immunity cycle simultaneously, underscoring its therapeutic potential in combination with existing checkpoint inhibitor treatments. Our preclinical and clinical studies suggest combining tomivosertib with a checkpoint inhibitor can overcome mechanisms of resistance to checkpoint inhibitors, resulting in prolonged sensitivity to checkpoint inhibitors and longer progression free survival (PFS). In addition, our preclinical data demonstrate that tomivosertib as a single agent promotes antitumor immunity that persists after stopping drug treatment.
We recently initiated the KICKSTART study, a randomized, double blind, placebo controlled Phase 2b study in patients with first line metastatic non-small cell lung cancer (NSCLC) with PD-L1 expression ≥ 50%, combining tomivosertib with pembrolizumab. KICKSTART will include two cohorts; patients who are treatment naïve and patients who have experienced an initial RECIST progression on pembrolizumab monotherapy. Both cohorts will be randomized 1:1 to tomivosertib + pembrolizumab or placebo + pembrolizumab. Previously we completed a 39 patient Phase 2a trial with tomivosertib in combination with checkpoint inhibitors. Tomivosertib is also being studied in combination with paclitaxel to treat patients with metastatic breast cancer in a Phase 2a trial in Canada fully funded by Stand Up to Cancer (SU2C) Canada.