Recruiting
Phase 1

LY4257496

Sponsor:

Eli Lilly and Company

Code:

NCT07114601

Conditions

Breast Neoplasms

Colorectal Neoplasms

Prostate Neoplasm

Endometrial Neoplasms

Neoplasm Metastasis

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

LY4257496

Standard of Care Anticancer Therapies

LY4257529

Study Details

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 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

Study ID

NCT07114601

Start date

Aug 6, 2025

Status verified date

Sep, 2026

Completion date

Apr, 2035

Anticipated

Primary completion date

Apr, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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
  • 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.

Exclusion Criteria:

  • 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.

Study Design

Enrollment

421 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: LY4257496 Phase 1a Dose Escalation (Cohort A1)

LY4257496 administered intravenously (IV)

experimental: LY4257496 Phase 1a Dose Optimization (Cohort A2)

LY4257496 administered IV

experimental: LY4257496 + Standard of Care Phase 1b Cohort B

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

experimental: LY4257496 Phase 1b Cohort C

Tumor specific cohort will receive LY4257496

experimental: LY4257496 Phase 1b Cohort D

Tumor specific cohort will receive LY4257496

Interventions

LY4257496

Administered IV

Standard of Care Anticancer Therapies

Fulvestrant, Imlunestrant, Aromatase Inhibitors, Capecitabine, Abemaciclib

LY4257529

Administered IV at select sites

Primary outcome measure

  • Phase 1a Dose Escalation: Maximum Tolerated Dose of LY4257496 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: From C1D1 through efficacy follow-up, estimated as Week 42. Cycle = 42 weeks ]

Central Contacts and Locations

Central contacts

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

1-317-615-4559LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

clinical_inquiry_hub@lilly.com

Locations

City of Hope

Recruiting

Duarte, California, United States, 91010

University of California, Los Angeles (UCLA)

Recruiting

Santa Monica, California, United States, 90404

Stanford University Medical Center

Recruiting

Stanford, California, United States, 94305

Moffitt

Recruiting

Tampa, Florida, United States, 33612

Emory University School of Medicine - Winship Cancer Institute

Recruiting

Atlanta, Georgia, United States, 30322

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Barbara Ann Karmanos Cancer Institute

Recruiting

Detroit, Michigan, United States, 48201

BAMF Health Inc.

Recruiting

Grand Rapids, Michigan, United States, 49503

Washington University

Recruiting

St Louis, Missouri, United States, 63110

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

Recruiting

New York, New York, United States, 10065

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Juravinski Cancer Centre

Recruiting

Hamilton, Canada, L8V 5C2

Sunnybrook Health Sciences Centre

Recruiting

Toronto, Canada, M4N 3M5

Princess Margaret Hospital

Recruiting

Toronto, Canada, M5G 2M9

More Information

Sponsor

Eli Lilly and Company

Last update posted

Sep 22, 2026

Last verified

Sep, 2026

Keywords

  • GRPR-positive

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-26. This information was provided to ClinicalTrials.gov by Eli Lilly and Company on 2026-09-22. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.