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

NCT07814417 | Not Yet Recruiting Phase 2 FDA Drug

• 3 other identifiers: 27858J3M-MC-JZQN2026-526138-23-00
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Colorectal Neoplasms

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  Baseline until Disease Progression (PD) or Participant Stops Study (Estimated up to 15 Months)

• Progression-Free Survival (PFS) Per RECIST v1.1

  Baseline to the Date of First Documented Progression of Disease or Participant Stops Study (Estimated up to 21 Months)

Secondary Outcomes (5)

• Overall Survival (OS)

  Baseline through End of Study (Estimated up to 21 months)

• Duration of Response (DoR)

  Baseline up to 15 months

• Disease Control Rate (DCR)

  Baseline up to 15 months

• Time to Response (TTR)

  Baseline up to 15 months

• Pharmacokinetics (PK): Plasma Concentrations of Olomorasib (LY3537982)

  Baseline up to 2 months

Study Arms (1)

Olomorasib + Cetuximab + mFOLFOX6

EXPERIMENTAL

Olomorasib administered orally; Cetuximab, fluorouracil, leucovorin \& oxaliplatin administered intravenously (IV)

Drug: Olomorasib; Drug: Cetuximab; Drug: Oxaliplatin; Drug: Leucovorin/levofolinate calcium; Drug: 5-fluorouracil

Interventions

Olomorasib DRUG

Administered orally

Also known as: LY3537982

Olomorasib + Cetuximab + mFOLFOX6

Cetuximab DRUG

Administered IV

Olomorasib + Cetuximab + mFOLFOX6

Oxaliplatin DRUG

Administered IV

Olomorasib + Cetuximab + mFOLFOX6

Leucovorin/levofolinate calcium DRUG

Administered IV

Olomorasib + Cetuximab + mFOLFOX6

5-fluorouracil DRUG

Administered IV

Olomorasib + Cetuximab + mFOLFOX6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• cycles of FOLFOX prior to study enrollment will be allowed for cases where immediate treatment is clinically indicated.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Central Study Contacts

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

CONTACT

1-317-615-4559; LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

CONTACT

clinical_inquiry_hub@lilly.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2026
• First Posted: September 11, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: September 11, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication or approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal should be approved by an independent review panel and researchers should sign a data sharing agreement.