TAX-TORC: A phase I trial of the combination of AZD2014 (dual mTORC1/mTORC2 inhibitor) and weekly paclitaxel in patients with solid tumors.

2607 Background: AZD2014 (A) is a dual mTORC1/mTORC2 inhibitor and a previous phase I study determined the maximal tolerated dose (MTD) of A to be 50 mg BD 7/7. We have shown high p-P70S6K levels in cancer cells derived from ascites is associated with resistance to subsequent chemotherapy in ovarian cancer. Additive apoptosis was seen when A was added to paclitaxel (P) in preclinical models. We thus set up a multicentre phase I trial to evaluate this combination. Methods: The aims of the study were to determine the MTD, profile safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of the combination of A+P. Dose escalation was performed using a 3+3 design. Patients (pts) with advanced cancers received 6 doses of weekly P (80 mg/m2) and escalating doses of A, BD 3/7, starting on the same day as P in 49-day cycles. Results: 12 pts have been evaluated so far at a fixed dose of P (80 mg/m2) and escalating doses of A; 25 mg (n=3), 50 mg (n=6) and 75 mg (n=3). Two pts had dos...