RECRUITING

A Study of LY4257496 in Participants With Cancer (OMNIRAY)

Conditions

Breast Neoplasms Colorectal Neoplasms Prostate Neoplasm Endometrial Neoplasms Neoplasm Metastasis GRPR-positive

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The main purpose of this study is to evaluate safety, tolerability, and efficacy of LY4257496 alone and as part of relevant standard of care (SOC) combination therapy in participants with Gastrin-releasing Peptide Receptor (GRPR)-positive advanced breast, colorectal, prostate, and endometrial cancer. The study will also evaluate the safety, tolerability, and efficacy of LY4257529 to identify cancer with high levels of a protein called GRPR. This is a 2-part study. Participation could last up to 36 weeks or until your tumor progresses.

Official Title

A Phase 1a/b Multicenter, Open-Label Trial to Evaluate Safety, Tolerability, and Dosimetry of LY4257496, a GRPR-Targeted Radioligand Therapy, in Adults With GRPR-Positive Advanced Solid Tumors (OMNIRAY)

Quick Facts

Study Start:2025-08-06

Study Completion:2035-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT07114601

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. Carcinosarcoma is eligible. Uterine leiomyosarcoma, adenosarcoma, or endometrial stromal sarcoma is not eligible. * 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.	* Phase 1a (Cohort A1 and A2) only: Previously received radiopharmaceutical or radioligand therapy. For participants with metastatic castration-resistant prostate cancer (mCRPC), prior ¹⁷⁷Lu-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. * Have known active hepatitis B virus (HBV) defined as positive for hepatitis B surface antigen (HBsAg) or Polymerase Chain Reaction (PCR) positive for HBV deoxyribonucleic acid (DNA) . Exception; Individuals with chronic HBV if they: * Have positive HBsAg * Are on suppressive antiviral therapy, as allowed per local regulations prior to C1D1 * Remain on the same antiviral treatment throughout study, and should follow local standards for continuation of therapy after completion of trial therapy. * Have undetectable HBV DNA \<14 days of C1D1. * Have known active hepatitis C virus (HCV) defined as positive for anti-HCV antibodies. Exception: Individuals previously treated for HCV if they: * Completed curative antiviral therapy. * Have an HCV viral load below the limit of quantification \<14 days of C1D1 and. * Are positive for anti-HCV antibodies and negative for HCV ribonucleic acid (RNA) before randomization. * Have untreated human immunodeficiency virus (HIV) infection. Exception: Individuals who have well-controlled HIV infection/disease and they: * Are on a stable and permitted antiretroviral therapy (ART) regimen without changes in drug or dose, for at least 4 weeks prior to C1D1 * Have a viral load of \<400 copies/mL\<14 days of C1D1. * Have a CD4+ T-cell count \>350 cells/mL \<14 days of C1D1. * Have not had an opportunistic infection within the past 12 months. * 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.

Inclusion Criteria

Exclusion 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. Carcinosarcoma is eligible. Uterine leiomyosarcoma, adenosarcoma, or endometrial stromal sarcoma is not eligible.
* 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.

* Phase 1a (Cohort A1 and A2) only: Previously received radiopharmaceutical or radioligand therapy. For participants with metastatic castration-resistant prostate cancer (mCRPC), prior ¹⁷⁷Lu-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.
* Have known active hepatitis B virus (HBV) defined as positive for hepatitis B surface antigen (HBsAg) or Polymerase Chain Reaction (PCR) positive for HBV deoxyribonucleic acid (DNA) . Exception; Individuals with chronic HBV if they:
* Have positive HBsAg
* Are on suppressive antiviral therapy, as allowed per local regulations prior to C1D1
* Remain on the same antiviral treatment throughout study, and should follow local standards for continuation of therapy after completion of trial therapy.
* Have undetectable HBV DNA \<14 days of C1D1.
* Have known active hepatitis C virus (HCV) defined as positive for anti-HCV antibodies. Exception: Individuals previously treated for HCV if they:
* Completed curative antiviral therapy.
* Have an HCV viral load below the limit of quantification \<14 days of C1D1 and.
* Are positive for anti-HCV antibodies and negative for HCV ribonucleic acid (RNA) before randomization.
* Have untreated human immunodeficiency virus (HIV) infection. Exception: Individuals who have well-controlled HIV infection/disease and they:
* Are on a stable and permitted antiretroviral therapy (ART) regimen without changes in drug or dose, for at least 4 weeks prior to C1D1
* Have a viral load of \<400 copies/mL\<14 days of C1D1.
* Have a CD4+ T-cell count \>350 cells/mL \<14 days of C1D1.
* Have not had an opportunistic infection within the past 12 months.
* 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.

Contacts and Locations

Study Contact

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

Principal Investigator

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)

STUDY_DIRECTOR

Eli Lilly and Company

Study Locations (Sites)

City of Hope

Duarte, California, 91010

United States

University of California, Los Angeles (UCLA)

Los Angeles, California, 90025

United States

Stanford University Medical Center

Stanford, California, 94305

United States

Biogenix Molecular, LLC

Miami, Florida, 33165

United States

Emory University School of Medicine - Winship Cancer Institute

Atlanta, Georgia, 30322

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201

United States

BAMF Health Inc.

Grand Rapids, Michigan, 49503

United States

Washington University

St Louis, Missouri, 63110

United States

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

Texas Oncology - DFW (Sammons CC)

Dallas, Texas, 75246

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Eli Lilly and Company

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), STUDY_DIRECTOR, 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 Registration Dates

Study Start Date2025-08-06

Study Completion Date2035-04

Study Record Updates

Study Start Date2025-08-06

Study Completion Date2035-04

Terms related to this study

Keywords Provided by Researchers

GRPR-positive

Additional Relevant MeSH Terms

Breast Neoplasms
Colorectal Neoplasms
Prostate Neoplasm
Endometrial Neoplasms
Neoplasm Metastasis