Breast NeoplasmsPhase 1OMNIRAYNCT07114601
A Study of LY4257496 in Participants With Cancer (OMNIRAY)
A Phase 1 study testing LY4257496 and LY4257529 in people with Breast Neoplasms and Colorectal Neoplasms, run by Eli Lilly and Company at 33 sites in 7 countries.
Trial 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 cancer, including but not limited to breast, colorectal, prostate… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Neoplasms, Colorectal Neoplasms, Prostate Neoplasm
- What is being tested?
- LY4257496 and LY4257529
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 421 participants
- Where
- 33 sitesin 7 countries
- Study dates
- 6 Aug 2025to Apr 2035
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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:
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- 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.
Trial locations and contacts
33 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or contact
Physicians interested in becoming principal investigators please contact contact
33 sites in 7 countries
United States16 sites, 15 recruiting
- Recruiting
Emory University School of Medicine - Winship Cancer Institute
Atlanta, Georgia, 30322
- Not yet recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
- Not yet recruiting
Texas Oncology - DFW (Sammons CC)
Dallas, Texas, 75246
- Recruiting
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
- Recruiting
City of Hope
Duarte, California, 91010
- Recruiting
BAMF Health Inc.
Grand Rapids, Michigan, 49503
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
- Active, not recruiting
Biogenix Molecular, LLC
Miami, Florida, 33165
- Not yet recruiting
New York University (NYU) Langone Medical Center
New York, New York, 10016
- Recruiting
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
New York, New York, 10065
- Not yet recruiting
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
- Recruiting
University of California, Los Angeles (UCLA)
Santa Monica, California, 90404
- Recruiting
Washington University
St Louis, Missouri, 63110
- Recruiting
Stanford University Medical Center
Stanford, California, 94305
- Recruiting
Moffitt
Tampa, Florida, 33612
Canada4 sites, 4 recruiting
- Recruiting
Juravinski Cancer Centre
Hamilton, L8V 5C2
- Not yet recruiting
Lady Davis Institute for Medical Research Jewish General Hospital
Montreal, H3T 1E2
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, M4N 3M5
- Recruiting
Princess Margaret Hospital
Toronto, M5G 2M9
Germany4 sites, 4 recruiting
- Not yet recruiting
Universitaetsklinikum Erlangen
Erlangen, 91054
- Recruiting
Universitaetsklinikum Essen
Essen, 45147
- Not yet recruiting
LMU Klinikum Muenchen-Campus Grosshadern
München, 80336
- Not yet recruiting
Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)
München, 81675
Japan3 sites, 3 recruiting
- Not yet recruiting
National Cancer Center Hospital East
Chiba, 277-8577
- Not yet recruiting
Kyoto University Hospital
Kyoto, 606-8507
- Not yet recruiting
The University of Osaka Hospital
Osaka, 565-0871
China2 sites, 2 recruiting
- Not yet recruiting
Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
Beijing, 100730
- Not yet recruiting
Tianjin Cancer Hospital Airport Hospital
Tianjin, 300060
France2 sites, 2 recruiting
- Not yet recruiting
Institut Curie
Paris, 75005
- Not yet recruiting
Institut de Cancerologie de l'Ouest - site St-Herblain
Saint-Herblain, 44805
Spain2 sites, 2 recruiting
- Not yet recruiting
Hospital Universitari Quiron Dexeus Barcelona
Barcelona, 08028
- Not yet recruiting
South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez Diaz
Madrid, 28040
About this study
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)
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.
- Conditions
- Breast Neoplasms, Colorectal Neoplasms, Prostate Neoplasm, Endometrial Neoplasms, Neoplasm Metastasis, Stomach Neoplasms
- Being tested
- LY4257496, Standard of Care Anticancer Therapies, LY4257529
- Keywords
- GRPR-positive
- Medical subject headings
- Breast Neoplasms, Colorectal Neoplasms, Prostatic Neoplasms, Endometrial Neoplasms, Neoplasm Metastasis, Stomach Neoplasms, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY4257496Drug
Administered IV
Standard of Care Anticancer TherapiesDrug
Fulvestrant, Imlunestrant, Aromatase Inhibitors, Capecitabine, Abemaciclib
LY4257529Diagnostic test
Administered IV at select sites
| Study group | Role | What they receive |
|---|---|---|
| LY4257496 Phase 1a Dose Escalation (Cohort A1) | Experimental | LY4257496 administered intravenously (IV) Receives: Drug: LY4257496; Diagnostic Test: LY4257529 |
| LY4257496 Phase 1a Dose Optimization (Cohort A2) | Experimental | LY4257496 administered IV Receives: 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) Receives: Drug: LY4257496; Drug: Standard of Care Anticancer Therapies; Diagnostic Test: LY4257529 |
| LY4257496 Phase 1b Cohort C | Experimental | Tumor specific cohort will receive LY4257496 Receives: Drug: LY4257496; Diagnostic Test: LY4257529 |
| LY4257496 Phase 1b Cohort D | Experimental | Tumor specific cohort will receive LY4257496 Receives: Drug: LY4257496; Diagnostic Test: LY4257529 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1a Dose Escalation: Maximum Tolerated Dose of LY4257496
Measured: 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
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: From end of injection through 1 day after injection
Phase 1a Dose Escalation PK: Area Under the Curve (AUC) of LY4257496
Measured: From C1D1 through 30 days after the last dose of study drug dose. Cycle = 30 days
Phase 1a Dose Escalation and Optimization PK: AUC of LY4257529
Measured: From end of injection through 1 day after injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2025
- Study start6 Aug 2025
- Primary completionApr 2030 (estimated)
- Study completionApr 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 421 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07114601
- Sponsor's protocol ID
- 27354
- Other IDs
- J6C-OX-JKFA, 2025-522367-15-00, 2025
- Acronym
- OMNIRAY
- Status last verified
- Oct 2026
- First submitted
- 30 Jul 2025
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No