Molecular Therapeutics Theme 3 Accomplishments

Theme 3: Validate clinical effectiveness of new agents and new protocols in interventional treatment trials

Scientific Accomplishments

In preclinical triple-negative breast cancer (TNBC) models, Drs. Boerner, Polin and Heilbrun, working with Dr. LoRusso, found that poly (ADP-ribose) polymerase (PARP) inhibitors such as veliparib (ABT-888) enhanced the activity of the topoisomerase 1 inhibitor irinotecan (CPT-11). Based on these results, a Phase I clinical trial was performed to examine the tolerability of combined veliparib/ironotecan in advanced solid tumor patients. Following the dose-escalation phase, an expansion cohort was opened to perform further biomarker and genomic correlative studies in two specific TNBC populations with the combined veliparib/irinotecan.

• Lead researchers - Drs. Boerner, Polin and Heilbrun.
• Collaborative researcher - Dr. Li

Dr. Gadgeelwas a Principal Investigators on a phase I/II study evaluating CH5424802 (alectinib), a second generation ALK (anaplastic lymphoma kinase) inhibitor in patients with ALK positive NSCLC (non-small cell lung cancer) whose disease had progressed following treatment with the first generation ALK inhibitor crizotinib. Based on the results of the phase II trial, the drug has received ‘breakthrough designation’ by the US FDA.

• Lead researchers - Dr. Gadgeel