FDA Grants Breakthrough Therapy Designation to Olomorasib
FDA Grants Breakthrough Therapy Designation to Olomorasib With Pembrolizumab for NSCLC
Olomorasib, combined with pembrolizumab, targets KRAS G12C-mutant NSCLC, addressing unmet needs in first-line treatment with high PD-L1 expression. NSCLC accounts for 80%-85% of lung cancer cases, with KRAS G12C mutations present in about 13% of patients.
The FDA has granted breakthrough therapy designation to olomorasib (Eli Lilly and Company) in combination with pembrolizumab (Keytruda; Merck), an anti-PD-1 therapy, for the first-line treatment of patients with unresectable advanced or metastatic non–small cell lung cancer (NSCLC) with a KRAS G12C mutation and PD-L1 expression greater than 50%.
Olomorasib’s Role in NSCLC Treatment
NSCLC is the most common type of lung cancer, accounting for approximately 80% to 85% of all lung cancer cases. This form of cancer causes normal cells in the lungs to become abnormal cells and multiply. While NSCLC grows slowly compared to small cell lung cancer (SCLC), it can spread to other parts of the body before symptoms develop. Symptoms of NSCLC include chest pain, chronic cough, coughing up blood, hoarseness, loss of appetite, shortness of breath, tiredness, and wheezing. If in the metastatic stage, NSCLC commonly spreads to the adrenal glands, bones, brain, liver, lymph nodes, and skin.
KRAS is the most common oncogene across all tumor types, as KRAS G12C mutations occur in about 13% of patients with NSCLC. As an investigational, oral, potent, and highly selective second-generation inhibitor of the KRAS G12C protein, olomorasib could offer further treatment for individuals with NSCLC, potentially offering greater than 90% target occupancy, which could lead to safer combinations with less toxicity.
Currently, olomorasib is being investigated as a combination treatment with pembrolizumab, with or without chemotherapy, for first-line treatment of advanced NSCLC; in combination with immunotherapy for the treatment of resected and unresectable NSCLC; and as a monotherapy and in combination in other advanced solid tumors.
Clinical Trial Results Supporting Designation for Olomorasib
The breakthrough therapy designation is based on data from the open-label, multicenter, phase 1/2 LOXO-RAS-20001 clinical trial (NCT04956640) and the dose optimization portion of the randomized, double-blind, placebo-controlled, global, phase 3 SUNRAY-01 clinical trial (NCT06890598).
