LY4257496 / Eli Lilly - LARVOL DELTA

OMNIRAY: A phase I study of the novel GRPR theranostic pair, LY4257529 (diagnostic) and LY4257496 (therapy), in patients with GRPR+ metastatic breast cancer and other advanced solid tumors (Trial in Progress) (ESMO-BC 2026) - P1 | "Dose expansion will enroll pts with ER+, HER2- MBC in multiple cohorts: B1 will receive LY4257496 alone, B2 LY4257496 plus ET, B3 LY4257496 plus capecitabine, and B4 LY4257496 plus ET and abemaciclib. Key objectives: Evaluate safety, antitumor activity, optimal dose, PK, biodistribution and dosimetry of LY4257496, and determine optimal LY4257529 dose and imaging timepoint. Table Table: 532TiP ETa, fulvestrant or imlunestrant; ETb, investigators' choice of aromatase inhibitor, fulvestrant, or imlunestrant; CRC, colorectal cancer"

Clinical • First-in-human • Metastases • P1 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • GRP-10 • HER-2

Characterization of LY4257496, a novel GRPR antagonist radiolabeled with lutetium-177 (AACR 2026) - P1 | "Efficacy was additive when 20MBq (Q14DX2) LY4257496 dose was given in combination with standard-of-care (SoC) therapies including imlunestrant, fulvestrant, and abemaciclib resulting in 40, 32, and 38% tumor regression, respectively at end of treatment (day 28). A competitive binding assay revealed that LY4257496 specifically bound to GRPR in human, mouse, and rat at comparable nanomolar potency of 8.5, 7.2, and 10.6 nM respectively. In biodistribution analyses, LY4257496 exhibited favorable pharmacokinetics with rapid tumor targeting and prolonged retention (% ID/g 22.6 at 1h, 11.6 at 24h), fast clearance from normal organs (all tissues below 3.5 % ID/g at 24h), and > 50% renal excretion. LY4257496 was well tolerated at 10, 20 and 30MBq (Q14DX2), and efficacy was dose dependent in T47D xenografts (26, 72, and 72 % TGI, respectively)."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • GRP-10 • HER-2 • PIK3CA

A Study of LY4257496 in Participants With Cancer (OMNIRAY) (clinicaltrials.gov) - P1 | N=421 | Recruiting | Sponsor: Eli Lilly and Company

Trial initiation date • Breast Cancer • Castration-Resistant Prostate Cancer • Colorectal Cancer • Endometrial Cancer • HER2 Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • ER • HER-2

J6C-OX-JKFA: A Study of LY4257496 in Participants With Cancer (OMNIRAY) (clinicaltrialsregister.eu) - P1 | N=53 | Not yet recruiting | Sponsor: Eli Lilly & Co.

New P1 trial • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Oncology • Prostate Cancer • Solid Tumor

A phase 1 study of LY4257496, a novel GRPR-targeted radioligand therapy, in patients with GRPR-positive metastatic ER+ breast cancer and other advanced solid tumors - OMNIRAY (Trial in Progress) (SABCS 2025) - "Dose expansion will enroll pts with ER+, HER2- MBC treated with LY4257496 monotherapy (cohort B1) and in combination with ET (cohort B2), capecitabine (cohort B3), or ET + abemaciclib (cohort B4)...Key exclusions include prior radiopharmaceutical (except 177Lu-PSMA-617 for mCRPC), recent pancreatitis, and untreated central nervous system metastases.Key study objectives: Evaluate safety, antitumor activity, optimal dose, PK, and biodistribution and dosimetry of LY4257496. Table ETa, fulvestrant or imlunestrant; ETb, investigators' choice of aromatase inhibitor, fulvestrant, or imlunestrant1Stoykow C, et al. Theranostics 2016, 6:1641-50"

Clinical • Metastases • P1 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • GRP-10 • HER-2

A Study of LY4257496 in Participants With Cancer (OMNIRAY) (clinicaltrials.gov) - P1 | N=421 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of LY4257496 in Participants With Cancer (OMNIRAY) (clinicaltrials.gov) - P1 | N=421 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Oncology • Prostate Cancer • Solid Tumor