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A Study of LY4257496 in Participants With Cancer (OMNIRAY)
NCT07114601 · Eli Lilly and Company
In plain English
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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)
About this study
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.
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. 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.
Exclusion Criteria:
* 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.
Study design
Enrollment target: 421 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-08-06
Estimated completion: 2035-04
Last updated: 2026-04-17
Interventions
Drug: LY4257496Drug: Standard of Care Anticancer TherapiesDiagnostic Test: LY4257529
Primary outcomes
- • 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)
Sponsor
Eli Lilly and Company · industry
Contacts & investigators
ContactTrial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or · contact · LillyTrials@Lilly.com · 1-317-615-4559
ContactPhysicians interested in becoming principal investigators please contact · contact · clinical_inquiry_hub@lilly.com
InvestigatorCall 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
All locations (28)
City of HopeNot Yet Recruiting
Duarte, California, United States
University of California, Los Angeles (UCLA)Recruiting
Santa Monica, California, United States
Stanford University Medical CenterRecruiting
Stanford, California, United States
Biogenix Molecular, LLCRecruiting
Miami, Florida, United States
MoffittNot Yet Recruiting
Tampa, Florida, United States
Emory University School of Medicine - Winship Cancer InstituteNot Yet Recruiting
Atlanta, Georgia, United States
Massachusetts General HospitalNot Yet Recruiting
Boston, Massachusetts, United States
Dana-Farber Cancer InstituteNot Yet Recruiting
Boston, Massachusetts, United States
Barbara Ann Karmanos Cancer InstituteRecruiting
Detroit, Michigan, United States
BAMF Health Inc.Recruiting
Grand Rapids, Michigan, United States
Washington UniversityRecruiting
St Louis, Missouri, United States
New York University (NYU) Langone Medical CenterNot Yet Recruiting
New York, New York, United States
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
Texas Oncology - DFW (Sammons CC)Not Yet Recruiting
Dallas, Texas, United States
MD Anderson Cancer CenterNot Yet Recruiting
Houston, Texas, United States
Juravinski Cancer CentreNot Yet Recruiting
Hamilton, Canada
Lady Davis Institute for Medical Research Jewish General HospitalNot Yet Recruiting
Montreal, Canada
Sunnybrook Health Sciences CentreNot Yet Recruiting
Toronto, Canada
Princess Margaret HospitalRecruiting
Toronto, Canada
Institut CurieNot Yet Recruiting
Paris, France
Institut de Cancerologie de l'Ouest - site St-HerblainNot Yet Recruiting
Saint-Herblain, France
Universitaetsklinikum ErlangenNot Yet Recruiting
Erlangen, Germany
Universitaetsklinikum EssenNot Yet Recruiting
Essen, Germany
LMU Klinikum Muenchen-Campus GrosshadernNot Yet Recruiting
München, Germany
Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)Not Yet Recruiting
München, Germany
National Cancer Center Hospital EastNot Yet Recruiting
Chiba, Japan
Kyoto University HospitalNot Yet Recruiting
Kyoto, Japan
Hospital Universitari Quiron Dexeus BarcelonaNot Yet Recruiting
Barcelona, Spain