A Study of Olomorasib (LY3537982) in Participants With Advanced Colorectal Cancer and a KRAS G12C Mutation

The main purpose of this study is to evaluate how well olomorasib is tolerated and what side effects may occur when combined with other interventions in participants with Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C-mutant, locally advanced colorectal cancer (CRC) that cannot be removed with surgery or has spread to other parts of the body. Blood tests will be performed to investigate how the body processes the study drug.

Inclusion Criteria: * Histologically or cytologically confirmed colorectal cancer (CRC) with Stage III or Stage IV disease, not suitable for curative intent radical surgery or radiation therapy. * Must have disease with evidence of KRAS G12C mutation * Have measurable disease per RECIST v1.1. * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Ability to swallow capsules. * Have adequate laboratory parameters. * Have not received treatment for their CRC that has spread to other parts of the body. * 1-2 cycles of FOLFOX prior to study enrollment will be allowed for cases where immediate treatment is clinically indicated. Exclusion Criteria: * Have active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease. * Have a clinically significant active malabsorption syndrome or other conditions likely to affect gastrointestinal absorption of the orally administered study treatments. * Have known untreated active central nervous system metastases or carcinomatous meningitis. * Have known additional malignancy that is progressing or has required treatment within the past 2 years. * Have uncontrolled, significant cardiovascular disease or cerebrovascular disease. * Have an active fungal, bacterial, or active, untreated viral infection. * Have human immunodeficiency virus (HIV) with a history of Kaposi's sarcoma or Multicentric Castleman's Disease. * Have known B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E gene mutation. * Have confirmed Microsatellite Instability-High/deficient Mismatch Repair (MSI-H/dMMR). * Individuals with known low or absent dihydropyrimidine dehydrogenase activity. * Have known positive Immunoglobulin E (IgE) antibodies against galactose-α-1,3-galactose (alpha-gal). * Have received adjuvant, neoadjuvant, concurrent chemoradiotherapy, or consolidation therapy if treatment was completed less than 6 months prior to enrollment. * Are pregnant, breastfeeding, or intend to become pregnant during the study.