A Study of LY4257496 in Participants With Cancer (OMNIRAY)

NCT07114601 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: 27354J6C-OX-JKFA2025-522367-15-00
• Study Type: interventional
• Target: 421
• Locations: 6 countries
• Sites: 28

Brief Summary

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.

Conditions

Breast Neoplasms; Colorectal Neoplasms; Prostate Neoplasm; Endometrial Neoplasms; Neoplasm Metastasis

Keywords

GRPR-positive

Outcome Measures

Primary Outcomes (3)

• Phase 1a Dose Escalation: Maximum Tolerated Dose of LY4257496

  From Cycle 1 Day 1 (C1D1) through 28 days after the first dose of study drug. Cycle = 28 days

• Phase 1a Dose Optimization: Number of Dose Limiting Toxicities of LY4257496

  From Cycle 1 Day 1 (C1D1) through 28 days after the first dose of study drug. Cycle = 28 days

• Phase 1b Dose Expansion and Optimization: Objective Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR)

  From C1D1 through efficacy follow-up, estimated as Week 42. Cycle = 42 weeks

Secondary Outcomes (7)

• Phase 1a Dose Escalation and Optimization: ORR: Percentage of Participants with Best Response of CR or PR

  From C1D1 through efficacy follow-up, estimated as Week 42. Cycle = 42 weeks

• Phase 1a Dose Escalation: Absorbed Dose Estimates (Gray (Gy)) of LY4257496 in Normal Organs

  From C1D1 through 30 days after the last dose of study drug dose. Cycle = 30 days

• Phase 1a Dose Escalation and Optimization: Absorbed Dose Estimates (Gy) of LY4257529 in Normal Organs

  From end of injection at Screening, and at Day 30 through 1 day after injection

• Phase 1a Dose Escalation Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY4257496

  From C1D1 through 30 days after the last dose of study drug dose. Cycle = 30 days

• Phase 1a Dose Escalation and Optimization PK: Cmax of LY4257529

  From end of injection through 1 day after injection

Study Arms (5)

LY4257496 Phase 1a Dose Escalation (Cohort A1)

EXPERIMENTAL

LY4257496 administered intravenously (IV)

Drug: LY4257496; Diagnostic Test: LY4257529

LY4257496 Phase 1a Dose Optimization (Cohort A2)

EXPERIMENTAL

LY4257496 administered IV

Drug: LY4257496; Diagnostic Test: LY4257529

LY4257496 + Standard of Care Phase 1b Cohort B

EXPERIMENTAL

Tumor specific cohort will receive LY4257496 alone or with standard of care anticancer therapy(ies)

Drug: LY4257496; Drug: Standard of Care Anticancer Therapies; Diagnostic Test: LY4257529

LY4257496 Phase 1b Cohort C

EXPERIMENTAL

Tumor specific cohort will receive LY4257496

Drug: LY4257496; Diagnostic Test: LY4257529

LY4257496 Phase 1b Cohort D

EXPERIMENTAL

Tumor specific cohort will receive LY4257496

Drug: LY4257496; Diagnostic Test: LY4257529

Interventions

LY4257496 DRUG

Administered IV

LY4257496 + Standard of Care Phase 1b Cohort B; LY4257496 Phase 1a Dose Escalation (Cohort A1); LY4257496 Phase 1a Dose Optimization (Cohort A2); LY4257496 Phase 1b Cohort C; LY4257496 Phase 1b Cohort D

Standard of Care Anticancer Therapies DRUG

Fulvestrant, Imlunestrant, Aromatase Inhibitors, Capecitabine, Abemaciclib

LY4257496 + Standard of Care Phase 1b Cohort B

LY4257529 DIAGNOSTIC_TEST

Administered IV at select sites

LY4257496 + Standard of Care Phase 1b Cohort B; LY4257496 Phase 1a Dose Escalation (Cohort A1); LY4257496 Phase 1a Dose Optimization (Cohort A2); LY4257496 Phase 1b Cohort C; LY4257496 Phase 1b Cohort D

Eligibility Criteria

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

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
• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (28)

City of Hope

Duarte, California, 91010, United States

NOT YET RECRUITING

University of California, Los Angeles (UCLA)

Santa Monica, California, 90404, United States

RECRUITING

Stanford University Medical Center

Stanford, California, 94305, United States

RECRUITING

Biogenix Molecular, LLC

Miami, Florida, 33165, United States

RECRUITING

Moffitt

Tampa, Florida, 33612, United States

NOT YET RECRUITING

Emory University School of Medicine - Winship Cancer Institute

Atlanta, Georgia, 30322, United States

NOT YET RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

NOT YET RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

BAMF Health Inc.

Grand Rapids, Michigan, 49503, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

New York University (NYU) Langone Medical Center

New York, New York, 10016, United States

NOT YET RECRUITING

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

New York, New York, 10065, United States

RECRUITING

Texas Oncology - DFW (Sammons CC)

Dallas, Texas, 75246, United States

NOT YET RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

NOT YET RECRUITING

Juravinski Cancer Centre

Hamilton, L8V 5C2, Canada

NOT YET RECRUITING

Lady Davis Institute for Medical Research Jewish General Hospital

Montreal, H3T 1E2, Canada

NOT YET RECRUITING

Sunnybrook Health Sciences Centre

Toronto, M4N 3M5, Canada

NOT YET RECRUITING

Princess Margaret Hospital

Toronto, M5G 2M9, Canada

RECRUITING

Institut Curie

Paris, 75005, France

NOT YET RECRUITING

Institut de Cancerologie de l'Ouest - site St-Herblain

Saint-Herblain, 44805, France

NOT YET RECRUITING

Universitaetsklinikum Erlangen

Erlangen, 91054, Germany

NOT YET RECRUITING

Universitaetsklinikum Essen

Essen, 45147, Germany

NOT YET RECRUITING

LMU Klinikum Muenchen-Campus Grosshadern

München, 80336, Germany

NOT YET RECRUITING

Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)

München, 81675, Germany

NOT YET RECRUITING

National Cancer Center Hospital East

Chiba, 277-8577, Japan

NOT YET RECRUITING

Kyoto University Hospital

Kyoto, 606-8507, Japan

NOT YET RECRUITING

Hospital Universitari Quiron Dexeus Barcelona

Barcelona, 08028, Spain

NOT YET RECRUITING

Related Links

• A Study of LY4257496 in Participants With Cancer (OMNIRAY)

MeSH Terms

Conditions

Breast Neoplasms; Colorectal Neoplasms; Prostatic Neoplasms; Endometrial Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2025
• First Posted: August 11, 2025
• Study Start: August 6, 2025
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2035
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); US (15); CA (4); JP (2); DE (4); FR (2)