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.
Must have histologically or cytologically proven diagnosis of locally advanced, unresectable, or metastatic cancer.
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.
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.