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PIPELINE > TRIAL OVERVIEW

Trial Information
Molecule Overview
Gastrin-Releasing Peptide Receptor Radioligand
LY4257496
Phase
1
Recruiting
Recruiting Info
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 Tumorsa
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Key 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 positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer
    • ER+/HER2 positive (HER2+) breast cancer
    • Colorectal carcinoma
    • Metastatic castration-resistant prostate cancer (mCRPC)
    • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤1
  • Must be able to comply with outpatient treatment, laboratory monitoring, imaging, and required clinic visits for the duration of trial participation
Key Exclusion Criteria
  • Phase 1a (Cohort A1 and A2) only: Previously received radiopharmaceutical or radioligand therapy. For participants with mCRPC, prior ¹⁷⁷Lu-prostate-specific membrane antigen (PSMA)-617 is permitted
  • Has a history of or ongoing acute pancreatitis within 1 year of screening
  • Received any prior hemi-body or whole-body radiotherapy, or prior external beam radiation therapy (EBRT) to >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 >2 years
  • Has known hypersensitivity to any component or excipient of LY4257496
a
This clinical trial is being conducted globally.
b
Participants enrolled in a dose level will receive the same dose every 6 weeks for a total of 4 or 6 cycles. After the first four cycles, two additional cycles may be permitted (up to 6 cycles in total).
c
Administered intravenously.
d
Includes fulvestrant or imlunestrant.
e
Administered orally.
f
Includes investigator’s choice of aromatase inhibitors, fulvestrant, or imlunestrant.
For information on trial enrollment, locations, and more, call 1-877-285-4559.
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