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

September 4, 2026 updated by: Eli Lilly and Company

A Phase 2, Open-Label Study to Evaluate the Safety and Efficacy of Olomorasib in Combination With Cetuximab and mFOLFOX6 in Participants With KRAS G12C-Mutant, Locally Advanced Unresectable or Metastatic Colorectal Cancer

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
  • Phone Number: 1-317-615-4559
  • Email: LillyTrials@Lilly.com

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Olomorasib + Cetuximab + mFOLFOX6
Olomorasib administered orally; Cetuximab, fluorouracil, leucovorin & oxaliplatin administered intravenously (IV)
Drug: Oxaliplatin
Administered IV
Drug: Cetuximab
Administered IV
Drug: 5-fluorouracil
Administered IV
Drug: Olomorasib
Administered orally
Other Names:
  • LY3537982
Drug: Leucovorin/levofolinate calcium
Administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame: Baseline until Disease Progression (PD) or Participant Stops Study (Estimated up to 15 Months)
Baseline until Disease Progression (PD) or Participant Stops Study (Estimated up to 15 Months)
Progression-Free Survival (PFS) Per RECIST v1.1
Time Frame: Baseline to the Date of First Documented Progression of Disease or Participant Stops Study (Estimated up to 21 Months)
Baseline to the Date of First Documented Progression of Disease or Participant Stops Study (Estimated up to 21 Months)

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall Survival (OS)
Time Frame: Baseline through End of Study (Estimated up to 21 months)
Baseline through End of Study (Estimated up to 21 months)
Duration of Response (DoR)
Time Frame: Baseline up to 15 months
Baseline up to 15 months
Disease Control Rate (DCR)
Time Frame: Baseline up to 15 months
Baseline up to 15 months
Time to Response (TTR)
Time Frame: Baseline up to 15 months
Baseline up to 15 months
Pharmacokinetics (PK): Plasma Concentrations of Olomorasib (LY3537982)
Time Frame: Baseline up to 2 months
Baseline up to 2 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eli Lilly and Company

Investigators

  • Study Director: 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 record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2026

Primary Completion (Estimated)

November 1, 2028

Study Completion (Estimated)

November 1, 2028

Study Registration Dates

First Submitted

September 4, 2026

First Submitted That Met QC Criteria

September 4, 2026

First Posted (Actual)

September 11, 2026

Study Record Updates

Last Update Posted (Actual)

September 11, 2026

Last Update Submitted That Met QC Criteria

September 4, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 27858
  • J3M-MC-JZQN (Other Identifier: Eli Lilly and Company)
  • 2026-526138-23-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

IPD Sharing 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.

IPD Sharing Access Criteria

A research proposal should be approved by an independent review panel and researchers should sign a data sharing agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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