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)

Cancer Categories

Breast,Gastrointestinal (GI),Genitourinary (GU),Gynecologic

Karmanos Trial ID

2025-079

NCT ID

NCT07114601

Age Group

Adult

Scope

National

Phase

Phase I

Principal Investigator

Anthony
Shields, M.D., Ph.D.
Oncology - Medical View Profile

Objective:

Phase 1a Dose Escalation and Optimization

Primary Objectives

Dose Escalation: To assess the safety and tolerability of LY4257496 monotherapy
Dose Optimization: To determine the optimal dose and schedule of LY4257496 monotherapy in ER+/HER2- BCa

Secondary Objectives

Dose Escalation and Optimization: To assess antitumor activity of LY4257496 monotherapy
Dose Escalation: To assess the biodistribution and radiation dosimetry of LY4257496
Dose Escalation: To characterize the PK properties of LY4257496

Phase 1b Dose Expansion/Optimization

Primary Objectives

Dose Expansion: To assess the antitumor activity of LY4257496
Dose Optimization: To determine the optimal dose and schedule based on safety and efficacy of LY4257496 monotherapy or in combination with SOC therapy

Secondary Objectives

Dose Expansion: To assess the safety and tolerability of LY4257496
Dose Expansion: To assess, for each Dose Expansion cohort, the antitumor activity of LY4257496

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Eligibility

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
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:

Previously received any radiopharmaceutical. For participants with metastatic castration-resistant prostate cancer (mCRPC), prior 177^Lu-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.
Has known active hepatitis B virus (HBV) (screening for HBV is not required for individuals who do not have a history of HBV, unless required by local regulations). Individuals with treated/chronic HBV are eligible for the trial provided they meet the following criteria:

Individuals with positive hepatitis B surface antigen (HBsAg) must be on permitted suppressive antiviral therapy prior to C1D1, remain on the same antiviral treatment throughout trial, and should follow local standards for continuation of therapy after completion of trial therapy.
Undetectable HBV deoxyribonucleic acid (DNA) less than or equal to 28 days of C1D1.

Has known active hepatitis C virus (HCV) (screening for HCV is not required for individuals who do not have a history of HCV unless required by local regulations). Individuals previously treated for HCV are eligible for the trial provided they meet the following criteria:

Completion of curative antiviral therapy.
HCV viral load below the limit of quantification less than or equal to 28 days of C1D1.
Negative hepatitis C antibody result OR, if positive, then must be hepatitis C RNA negative.

Has known untreated human immunodeficiency virus (HIV) infection (screening for HIV is not required unless required by local regulations). Participants on permitted antiretroviral therapy (ART) and who have well-controlled HIV infection/disease are eligible provided they meet the following criteria:

Must be on a stable and permitted ART regimen without changes in drug or dose, for at least 4 weeks prior to C1D1 and have a viral load of <400 copies per mL prior to less than or equal to 28 days of C1D1.
CD4+ T-cell count greater than or equal to 350 cells/uL less than or equal to 28 days of C1D1.

Has an active second malignancy unless in remission with life expectancy greater than 2 years.

Locations

Karmanos Cancer Institute - Detroit Headquarters

4100 John R
Detroit, MI 48201
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Phone: 1-800-527-6266

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 1-800-527-6266

Applicable Disease Site

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