Eli Lilly and Company (Lilly, NYSE: LLY) has released updated data from its ongoing Phase 1/2 clinical trial for olomorasib, showcasing significant advancements in the treatment of advanced solid tumors with KRAS G12C mutations. The data, which highlights both monotherapy and combination therapy results with Merck’s KEYTRUDA (pembrolizumab), was presented at the prestigious 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

Clinical Results

The Phase 1/2 study, known as LOXO-RAS-20001, is investigating olomorasib as a monotherapy in patients with a variety of KRAS G12C-mutant advanced solid tumors and in combination with KEYTRUDA in patients with KRAS G12C-mutant advanced non-small cell lung cancer (NSCLC). Olomorasib, an investigational oral therapy, stands out as a potent and highly selective second-generation inhibitor of the KRAS G12C protein, designed to address significant unmet needs in cancer treatment.

“Despite recent advances, there remains a significant unmet need for patients with KRAS G12C-mutant cancers,” said Timothy Burns, M.D., Ph.D., Associate Professor of Medicine at the University of Pittsburgh Medical Center Hillman Cancer Center. “These data show efficacy with olomorasib across tumor types and, importantly, tolerability that suggests it can be combined with immunotherapy, the backbone of first-line treatment for KRAS-mutant NSCLC.”

Monotherapy and Combination Therapy Insights

In the trial, olomorasib demonstrated promising efficacy as a monotherapy, achieving an objective response rate (ORR) of 35% across non-colorectal cancer (CRC) solid tumors, with a median progression-free survival (PFS) of 7.1 months. For patients with NSCLC naive to KRAS G12C inhibitors, the median PFS was an encouraging 7.9 months.

The combination of olomorasib with pembrolizumab in KRAS G12C-mutant advanced NSCLC also showed remarkable results, particularly in first-line metastatic settings where the ORR reached 77%, and the median PFS has not yet been reached, indicating sustained effectiveness.

Safety and Tolerability Profile of Olomorasib

The safety profile of olomorasib was consistent with previous studies, with most treatment-related adverse events (TRAEs) being of low grade. The most common TRAEs included diarrhea, nausea, and fatigue, with discontinuation rates due to adverse effects remaining low, underscoring the treatment’s manageability.

Future Directions and Implications

Looking forward, Eli Lilly is continuing to explore olomorasib’s potential through the SUNRAY-01 study, a global, registrational trial investigating the drug in combination with pembrolizumab-containing regimens for first-line treatment of KRAS G12C-mutant NSCLC.

“As a second-generation KRAS G12C inhibitor, olomorasib was specifically designed to offer a differentiated profile that could potentially overcome limitations of currently available treatment options,” said David Hyman, M.D., chief medical officer at Lilly. “With these updated data, we are pleased to see our thesis for olomorasib continuing to translate clinically.”

The latest results from Eli Lilly’s study represent a significant stride in cancer research, particularly for patients with KRAS G12C-mutant NSCLC, where new treatment options are critically needed. These findings not only reinforce the potential of targeted therapies in oncology but also highlight the importance of strategic collaborations in advancing cancer treatment.

  ASCO 2024, Cancer treatment, Eli Lilly, KRAS G12C inhibitor, Lilly, NSCLC therapy, olomorasib