A Study of LY4257496 in Participants With Cancer (OMNIRAY)

Recruiting now · Phase 1

Conditions studied: Breast Neoplasms, Colorectal Neoplasms, Prostate Neoplasm, Endometrial Neoplasms, Neoplasm Metastasis, Stomach Neoplasms, Esophageal Neoplasms

In brief

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 cancer, including but not limited to breast, colorectal, prostate, endometrial, esophageal, gastroesophageal (GE) junction, and gastric 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.

Key facts

Study ID

NCT07114601

Run by

Eli Lilly and Company

People needed

421

Starts

2025-08-06

Expected to finish

2035-04-01

Last updated by the study team

2026-08-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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
• Esophageal squamous cell carcinoma
• Adenocarcinoma of the stomach, gastroesophageal junction, or esophagus
• Colorectal carcinoma
• Metastatic castration-resistant prostate cancer
• Endometrial carcinoma. Carcinosarcoma is eligible. Uterine leiomyosarcoma, adenosarcoma, or endometrial stromal sarcoma is not eligible.
• Low-grade papillary serous ovarian cancer
• Other non-Central Nervous System (CNS) primary GRPR-positive solid tumors (Cohorts A1 dose escalation and D1 dose expansion only)
• 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.

You may not qualify if…

• Phase 1a (Cohort A1 and A2) only: Previously received radiopharmaceutical or radioligand therapy. For participants with prostate cancer, prior ¹⁷⁷Lu-prostate-specific membrane antigen (PSMA) 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). 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). 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.

Where it is running

• City of Hope — Duarte, California, United States (enrolling)
• University of California, Los Angeles (UCLA) — Santa Monica, California, United States (enrolling)
• Stanford University Medical Center — Stanford, California, United States (enrolling)
• Biogenix Molecular, LLC — Miami, Florida, United States (enrolling)
• Moffitt — Tampa, Florida, United States (enrolling)
• Emory University School of Medicine - Winship Cancer Institute — Atlanta, Georgia, United States (enrolling)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)
• Barbara Ann Karmanos Cancer Institute — Detroit, Michigan, United States (enrolling)
• BAMF Health Inc. — Grand Rapids, Michigan, United States (enrolling)
• Washington University — St Louis, Missouri, United States (enrolling)
• David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center — New York, New York, United States (enrolling)
• MD Anderson Cancer Center — Houston, Texas, United States (enrolling)
• Juravinski Cancer Centre — Hamilton, Canada (enrolling)
• Sunnybrook Health Sciences Centre — Toronto, Canada (enrolling)
• Princess Margaret Hospital — Toronto, Canada (enrolling)
• National Cancer Center Hospital East — Chiba, Japan
• Kyoto University Hospital — Kyoto, Japan
• Lady Davis Institute for Medical Research Jewish General Hospital — Montreal, Canada
• Hospital Universitari Quiron Dexeus Barcelona — Barcelona, Spain
• South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez Diaz — Madrid, Spain
• Peking Union Medical College Hospital of Chinese Academy of Medical Sciences — Beijing, China
• Tianjin Cancer Hospital Airport Hospital — Tianjin, China
• Institut Curie — Paris, France
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Institut de Cancerologie de l'Ouest - site St-Herblain — Saint-Herblain, France

Full record on ClinicalTrials.gov

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