Pharmacodynamics and Biomarker Assessments
tumor
DISEASE PROGRESSION, TUMOR
Archival tumor tissue (not older than 6 months prior to screening) or fresh tumor biopsy was required to characterize Notch alteration status by targeted genomic sequencing and/or NICD1 expression (via IHC) among the confirmatory cohort at baseline. Repeat biopsy on cycle 2 day 15 and at disease progression was optional. Serial whole blood samples (and/or bone marrow samples and saliva among patients with T-ALL/T-LBL) were obtained on day 1 of cycles 1–6 to evaluate the dynamics of Notch gene expression. Peripheral blood was collected with PaxGene tubes and frozen at −20°C until processing. RNA was extracted (Qiagen RNeasy Micro kit) from peripheral whole blood and analyzed by Nanostring with percent change in expression levels reported with respect to baseline normalized values.