New Data from Phase 1/2 Study of Olomorasib in KRAS G12C-Mutant Solid Tumors at 2024 ASCO Meeting

Eli Lilly and Company has presented updated findings from their ongoing Phase 1/2 trial evaluating the drug olomorasib. This investigational, oral, second-generation inhibitor targets the KRAS G12C protein, a common mutation in various solid tumors, including non-small cell lung cancer (NSCLC). The data was revealed at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

Olomorasib has shown significant monotherapy activity in a range of KRAS G12C-mutant advanced solid tumors. These tumors include NSCLC, colorectal cancer (CRC), and pancreatic cancer, among others. The study involved 184 patients, with 42 NSCLC patients who had not previously received a KRAS G12C inhibitor, and 41 who had. Among the other patients, 32 had CRC, 24 had pancreatic cancer, and 45 had other types of solid tumors. These patients had undergone a median of three prior lines of therapy.

The efficacy of olomorasib as a monotherapy was evident, with an overall response rate (ORR) of 35% in non-CRC solid tumors and a median progression-free survival (PFS) of 7.1 months for KRAS G12C inhibitor-naive non-CRC tumors. For NSCLC patients previously treated with a KRAS G12C inhibitor, the ORR was 41%, and their median PFS was 8.1 months. Importantly, the drug demonstrated preliminary central nervous system (CNS) activity in patients with measurable brain metastases.

Adverse effects (AEs) associated with olomorasib were typically mild, with diarrhea, nausea, and fatigue being the most common. Treatment-related adverse events (TRAEs) led to the discontinuation of the drug in only 1% of cases.

Additionally, olomorasib's combination with Merck's pembrolizumab (KEYTRUDA®) was evaluated in patients with advanced NSCLC. This part of the trial included 64 patients who had received up to two prior lines of therapy. Among those treated in the first-line metastatic setting, the combination therapy achieved an ORR of 77%. The trial continues to demonstrate promising results, with median PFS not yet reached. Common TRAEs included diarrhea, increased ALT, pruritus, increased AST, and fatigue. Discontinuation rates due to TRAEs were low, with only 3% of patients stopping olomorasib and 11% discontinuing pembrolizumab.

The SUNRAY-01 global study is investigating olomorasib in combination with pembrolizumab, with or without chemotherapy, in first-line NSCLC treatment. This study aims to provide more options for patients with KRAS G12C-mutant lung cancers, where current treatments may be limited.

Olomorasib, also known as LY3537982, was designed as a potent and selective inhibitor of the KRAS G12C protein, aiming to address the limitations of existing treatments. Its pharmacokinetic properties allow for high target occupancy and potency, making it effective as both a standalone treatment and in combination with immunotherapies like pembrolizumab.

Eli Lilly's commitment to advancing cancer treatments is underscored by their ongoing trials and research into olomorasib. As the company continues to explore the full potential of this drug, they aim to improve outcomes for patients with KRAS G12C-mutant cancers, particularly those with NSCLC.

The exploration of olomorasib is part of Eli Lilly's broader mission to develop innovative therapies that address significant unmet needs in oncology and beyond. Their work on olomorasib reflects a dedication to improving patient care through scientific and clinical advancement.