MLN9708, an investigational proteasome inhibitor, in patients (pts) with relapsed/refractory lymphoma: Emerging data from a phase I dose-escalation study.

8064 Background: MLN9708 is a reversible, orally bioavailable, specific 20S proteasome inhibitor. This study (NCT00893464) studied the safety and determined the MTD of IV MLN9708 in pts with relapsed/refractory lymphoma, and characterized pharmacokinetics (PK) and pharmacodynamics (PD). Methods: Pts aged ≥18 yrs who had failed ≥2 chemotherapeutic regimens received IV MLN9708 on days 1, 8, and 15 of 28-day cycles until disease progression or unacceptable toxicity. One pt was enrolled at the 0.125 mg/m2 starting dose; dose doubling proceeded with 1 pt at each dose up to 1.0 mg/m2. Dose escalation occurred in ≤40% increments using a standard 3+3 scheme based on DLT occurrence in cycle 1. Blood samples were collected at multiple time points after dosing on days 1 and 15 of cycle 1 for PK/PD analyses. Results: At data cut-off (Dec 1 2011), 21 pts had been enrolled and treated: 1 each at 0.125, 0.25, 0.5 and 1 mg/m2, 4 at 1.4 mg/m2, 7 at 1.76 mg/m2, and 6 at 2.34 mg/m2. Median age was 57 yrs (range 23–78); 57% ...