LY-4066434 / Eli Lilly - LARVOL DELTA

LY4050784, a selective inhibitor of SMARCA2, demonstrates synergistic activity in combinations with pembrolizumab or KRAS inhibitors (AACR 2025) - P1 | "LY4050784 demonstrated robust activity in vitro and in vivo when combined with standard lung cancer chemotherapies (paclitaxel, cisplatin, and pemetrexed)...Finally, we explored the activity of LY4050784 in combination with both mutant-selective KRAS G12C and G12D inhibitors (olomorasib and LY3962673, respectively) and the isoform-selective pan-KRAS inhibitor LY4066434...These results demonstrate that LY4050784 exhibits robust antitumor activity in combination with chemotherapy, pembrolizumab, and multiple KRAS inhibitors in preclinical models of SMARCA4-mutant cancers. Investigation of these combinations clinically is warranted"

IO biomarker • Colon Cancer • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS • SMARCA2 • SMARCA4

LY4066434, an oral small molecule pan-KRAS inhibitor, demonstrates robust anti-tumor activity in KRAS-mutant models, including in the CNS (AACR 2025) - P1 | "LY4066434 when combined with cetuximab showed enhanced antitumor activity in PDX models of NSCLC, pancreatic, and colorectal cancers with various KRAS mutations. Oct 11-15, 2023. Boston, MA."

Brain Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • HRAS • KRAS • NRAS

Lilly announces details of presentations at 2025 American Association for Cancer Research (AACR) Annual Meeting (PRNewswire) - "In an oral presentation, Lilly, in collaboration with Foghorn Therapeutics, will present new preclinical data for LY4050784, a selective inhibitor of SMARCA2, in combination with chemotherapy, pembrolizumab, and KRAS inhibitors in preclinical models of SMARCA4 mutant cancers. Preclinical data for LY4066434, a pan-KRAS inhibitor that is highly selective over HRAS and NRAS, will also be presented."

Preclinical • Solid Tumor

A Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors (clinicaltrials.gov) - P1 | N=750 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

A Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors (clinicaltrials.gov) - P1 | N=750 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Loxo@Lilly Unveils Three New Oncology Programs at 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (PRNewswire) - "Loxo@Lilly...announced that preclinical data for agents targeting KRAS G12D, multiple oncogenic KRAS mutations and Nectin-4, will be presented at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics...These programs are among the next slate of new oncology agents planned to enter clinical trials for Loxo@Lilly in 2024. The poster presentations will include preclinical characterization data for a highly potent inhibitor of KRAS G12D that is selective against wild-type KRAS, a highly potent and isoform-selective pan-KRAS inhibitor with activity against a broad spectrum of the most common activating KRAS mutations and high selectivity over wild-type HRAS and NRAS, and a fully human monoclonal anti-Nectin-4 antibody conjugated to a topoisomerase I (TOPO 1) inhibitor."

New trial • Preclinical • Oncology