A Study of LY4257496 in Participants With Cancer (OMNIRAY)

Launched by ELI LILLY AND COMPANY · Aug 5, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new medicine called LY4257496 to see if it is safe and effective for treating certain advanced cancers that have spread, including breast, colorectal (colon), prostate, and endometrial (lining of the uterus) cancers. The study focuses on patients whose tumors have a specific marker called GRPR, which helps the medicine target the cancer cells. This trial has two parts and may last up to about 9 months or until the cancer stops responding to treatment.

People who might be eligible to join are adults between 65 and 74 years old who have advanced or metastatic cancer confirmed by tests like biopsies and scans. Their cancer must show the GRPR marker, and they need to be well enough to attend regular outpatient visits for treatment and monitoring. Participants should not have had certain previous treatments like some types of radiation or specific radioactive medicines, and they must not have active infections like untreated hepatitis or HIV. During the trial, participants will receive LY4257496 alone or with other standard treatments, and the study team will closely watch for safety and how well the cancer responds. If you or a loved one fits these criteria and are interested, this study might offer a new option to help manage advanced cancer.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Must have histologically or cytologically proven diagnosis of locally advanced, unresectable, or metastatic cancer.
• * Must be assessed by computed tomography (CT)/magnetic resonance imaging (MRI) to confirm at least 1 of the following:
• • At least 1 measurable target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• • If only bone lesions are present without a soft-tissue component, a bone scan or MRI must confirm at least 2 detectable lesions considered to represent active metastases
• • Must have GRPR-positive disease, defined by investigator assessment of GRPR imaging.
• * Must have the following histologically or cytologically confirmed diagnosis:
• • Estrogen receptor (ER+)/human epidermal growth factor receptor 2 (HER2-) breast cancer
• • ER+/HER2+ breast cancer
• • Colorectal carcinoma
• • Metastatic castration-resistant prostate cancer
• • Endometrial carcinoma
• • Other GRPR-positive solid tumor
• • For participants with breast cancer diagnosis, where possible, ER and HER2 status should be assessed from the most recent tissue biopsy taken at the time of presentation with recurrent or metastatic disease.
• • To fulfill the requirement for ER+ disease by local testing, a tumor must express the ER immunohistochemistry, as defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
• • HER2 status should be determined by local testing, as defined in the relevant ASCO/CAP Guidelines.
• • Must have an Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 1.
• • Must be able to comply with outpatient treatment, laboratory monitoring, imaging, and required clinic visits for the duration of trial participation.
• Exclusion Criteria:
• • Previously received any radiopharmaceutical. For participants with metastatic castration-resistant prostate cancer (mCRPC), prior 177\^Lu-prostate-specific membrane antigen (PSMA)-617 is permitted.
• • Has a history of ongoing acute pancreatitis within 1 year of screening.
• • Previously received any prior hemi-body or whole-body radiotherapy, or prior external beam radiation therapy (EBRT) to greater than 25% of the bone marrow.
• • A bone superscan, defined as a bone scan that demonstrates markedly increased skeletal radioisotope uptake relative to soft tissues in association with absent or faint genitourinary tract activity.
• • Has evidence of ongoing and untreated urinary tract obstruction or unmanageable urinary incontinence.
• * Has known active hepatitis B virus (HBV) (screening for HBV is not required for individuals who do not have a history of HBV, unless required by local regulations). Individuals with treated/chronic HBV are eligible for the trial provided they meet the following criteria:
• • Individuals with positive hepatitis B surface antigen (HBsAg) must be on permitted suppressive antiviral therapy prior to C1D1, remain on the same antiviral treatment throughout trial, and should follow local standards for continuation of therapy after completion of trial therapy.
• • Undetectable HBV deoxyribonucleic acid (DNA) less than or equal to 28 days of C1D1.
• * Has known active hepatitis C virus (HCV) (screening for HCV is not required for individuals who do not have a history of HCV unless required by local regulations). Individuals previously treated for HCV are eligible for the trial provided they meet the following criteria:
• • Completion of curative antiviral therapy.
• • HCV viral load below the limit of quantification less than or equal to 28 days of C1D1.
• • Negative hepatitis C antibody result OR, if positive, then must be hepatitis C RNA negative.
• * Has known untreated human immunodeficiency virus (HIV) infection (screening for HIV is not required unless required by local regulations). Participants on permitted antiretroviral therapy (ART) and who have well-controlled HIV infection/disease are eligible provided they meet the following criteria:
• • Must be on a stable and permitted ART regimen without changes in drug or dose, for at least 4 weeks prior to C1D1 and have a viral load of \<400 copies per mL prior to less than or equal to 28 days of C1D1.
• • CD4+ T-cell count greater than or equal to 350 cells/uL less than or equal to 28 days of C1D1.
• • Has an active second malignancy unless in remission with life expectancy greater than 2 years.
• • Has known hypersensitivity to any component or excipient of LY4257496.