Over the past several years, a class of drugs called checkpoint inhibitors (primarily anti-PD-(L)1 therapies), have emerged as an important new therapeutic area modality for the treatment of cancer. While checkpoint inhibitor treatment is very effective for some patients for a variety of cancers, these agents are generally not curative – including for people with non-small cell lung cancer (NSCLC). The majority of patients ultimately progress on their checkpoint inhibitor therapy.
There are approximately 70,000 U.S. patients with metastatic NSCLC who have PD-L1 expression ≥1%. The large majority of these patients are eligible to enroll in KICKSTART, a double-blind, randomized, placebo-controlled Phase 2b trial of tomivosertib combined with pembrolizumab in patients with metastatic NSCLC. We are enrolling two separate groups of patients in KICKSTART: The first group, with low PD-L1 expression, will receive pembrolizumab combined with platinum chemotherapy as their frontline treatment and will receive a combination of tomivosertib or placebo plus pembrolizumab after completing their platinum treatment without disease progression in the maintenance setting. The second group, with high PD-L1 expression, will receive tomivosertib or placebo plus pembrolizumab as their frontline treatment.
We are also investigating our second product candidate, zotatifin, in KRAS-mutant NSCLC as a single agent in non-G12C patients and in combination with a G12C KRAS inhibitor for patients who are G12C-positive. Activating KRAS mutations occur in approximately 25% of patients with NSCLC, an area in which there is a significant need to improve treatment outcome.