DS-7423 / Daiichi Sankyo - LARVOL DELTA

A call for global harmonization of phase I oncology trials: Results from two parallel, first-in-human phase I studies of DS-7423, an oral PI3K/mTOR dual inhibitor in advanced solid tumors conducted in the United States and Japan. (ASCO 2017) - P1; "Despite differences in BW, BMI, and ethnicity, DS-7423 showed no difference in PK, PD, toxicity or efficacy between populations. We found near identical RP2D in phase I oncology studies and approved doses in pivotal studies. This supports increased international collaboration in the conduct of phase I oncology trials."

Clinical • P1 data • Biliary Cancer • Biosimilar • Immunology • Non Small Cell Lung Cancer • Sarcoma

HER2 mediates PSMA/mGluR1-driven resistance to the DS-7423 dual PI3K/mTOR inhibitor in PTEN wild-type prostate cancer models. (PubMed, Mol Cancer Ther) - "Concomitant targeting of PI3K/mTOR with either HER2 or mGluR1 inhibitors results in decreased cell survival and tumor growth in xenograft studies. Our results suggest a novel therapeutic possibility for PTEN wild-type-PI3K/AKT mutant prostate cancer patients based in the combination of PI3K/mTOR blockade with HER2 or mGluR1 inhibitors."

Journal • Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • ERBB3 • HER-2 • PTEN

Anti-tumor activity of dual inhibition of phosphatidylinositol 3-kinase and MDM2 against clear cell ovarian carcinoma. (PubMed, Gynecol Oncol) - "A combination therapy targeting the PI3K pathway and MDM2 might be a promising therapeutic strategy in CCOC."

Journal • PARP Biomarker