BAY 1125976 / Bayer - LARVOL DELTA

Ba/F3 AKT engineering cell lines, a powerful platform for novel drug discovery (EORTC-NCI-AACR 2024) - "The failures of AKT inhibitors LY2780301 and Bayer's BAY1125976 demonstrate that there are significant challenges and complexities in developing AKT pathway inhibitors. Currently, the most advanced AKT inhibitor in the world is capivasertib from AstraZeneca , capivasertib is primarily used in HR+ breast cancer and triple-negative breast cancer.Our team has generated 23 Ba/F3-AKT engineered cell lines, which are useful models for in vitro and in vivo drug discovery, including nearly all clinically significant mutations, such as the common AKT1/2-E17K mutations and the rare L52R, Q79K, and D323H mutations.The Ba/F3-AKT engineered cell line can be used to develop and evaluate next-generation AKT inhibitors, as well as to explore newly acquired AKT resistance mutations."

Preclinical • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AKT2 • PIK3CA • PTEN

Ba/F3 AKT engineering cell lines, a useful platform for novel drug discovery (AACR 2024) - "The failures of AKT inhibitors LY2780301 and Bayer's BAY1125976 demonstrate the significant challenges and complexities in developing inhibitors of the AKT pathway. Currently, the most advanced AKT inhibitor globally is AstraZeneca's capivasertib, which is primarily indicated for HR+ breast cancer and triple-negative breast cancer. Our group has generated 21 Ba/F3-AKT engineering cell lines, as useful models for novel drug discovery in vitro and in vivo, almost all clinically significant mutations were included, such as common mutations AKT1/2-E17K as well as rare mutations L52R, Q79K, D323H, and others. The Ba/F3-AKT engineering cell lines can be useful for developing and evaluating next-generation AKT inhibitors and exploring newly acquired resistance mutations in AKT."

Preclinical • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AKT2 • PIK3CA • PTEN

Phase I dose-escalation study of the allosteric AKT inhibitor BAY 1125976 in advanced solid cancer (AACR 2019) - P1; "Tolerable doses of BAY 1125976 resulted in inhibition of AKT1/2 signaling in platelet rich plasma samples. A notable CBR of 27.9% was achieved at the R2D of BAY 1125976; however PR was seen in only 1 patient with HR+ MBC. Clinical benefit did not correlate with presence of AKT mutations."

BRCA Biomarker • P1 data • Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Phase 1 Dose Escalation Study of the Allosteric AKT Inhibitor BAY 1125976 in Advanced Solid Cancer-Lack of Association between Activating AKT Mutation and AKT Inhibition-Derived Efficacy. (PubMed, Cancers (Basel)) - P1; "BAY 1125976 was well tolerated and inhibited AKT1/2 signaling but did not lead to radiologic or clinical tumor responses. Thus, the refinement of a selection of biomarkers for AKT inhibitors is needed to improve their monotherapy activity."

Clinical • Journal • P1 data