RG7775 / Roche - LARVOL DELTA

A phase I study of the MDM2 antagonist RO6839921, a pegylated intravenous prodrug of idasanutlin, in patients with AML (EORTC-NCI-AACR 2017) - "RO6839921 shows a PK profile similar to idasanutlin. The MTD of 250 mg AP qd x 5 days has a manageable safety profile in R/R AML at ~25% of the idasanutlin dose identified for development in this population. Single-agent antileukemic activity is observed in 42% pts overall, including 4 of 8 pts (50%) at the MTD."

Biomarker • Clinical • Next-Generation Sequencing • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Phase 1 study of the MDM2 antagonist RO6839921 in patients with acute myeloid leukemia. (PubMed, Invest New Drugs) - P1; "There was not sufficient differentiation or improvement in the biologic or safety profile compared with oral idasanutlin to support continued development of RO6839921. NCT02098967."

Clinical • Journal • P1 data • C18orf8 • GDF15 • TP53

A phase 1 study of the MDM2 antagonist RO6839921, a pegylated prodrug of idasanutlin, in patients with advanced solid tumors. (PubMed, Invest New Drugs) - P1; "Conclusions RO6839921 showed reduced pharmacokinetic exposure variability and a safety profile comparable with that of oral idasanutlin. Although this study indicated that RO6839921 could be administered to patients, the results did not provide sufficient differentiation or improvement in the biologic or safety profile compared with oral idasanutlin to support continued development."

Clinical • Journal • P1 data • C18orf8 • GDF15

Preclinical evaluation of the first intravenous small molecule MDM2 antagonist alone and in combination with temozolomide in neuroblastoma. (PubMed, Int J Cancer) - "Overall, RO6839921 had a favourable pharmacokinetic profile consistent with intermittent dosing and was well tolerated alone and in combination. These preclinical studies support the further development of idasanutlin in combination with temozolomide in neuroblastoma in early phase clinical trials."

Combination therapy • Journal • Preclinical