Safety Trial Supports Weekly Dosing of Oral 20S Proteasome Inhibitor in Multiple Myeloma Patients

An ongoing phase I study of patients who have experienced relapsed and/or refractory multiple myeloma has found that this population was largely able to tolerate a new oral 20S proteasome inhibitor after receiving other prior treatments.

An abstract on MLN9708 was presented this week at the 2013 Annual Meeting of the American Society of Clinical Oncology in Chicago that reported the safety, activity, and pharmacokinetics of the agent in a phase I trial.

Researchers led by Shaji Kumar, MD, at the Mayo Clinic in Rochester, Minnesota, are investigating MLN9708, a medication that had decreased tumor activity in in vivo models of multiple myeloma. MLN0708 was administered weekly to a group of 60 patients, including 33 males. Study participants ranged from 40 to79 years, with a median age of 64. Patients received MLN9708 at a dose of 0.24-3.95 mg/m² (dose-escalation phase, 32 patients), and at the maximum-tolerated dose of 2.97 mg/m² in relapsed/refectory, bortezomib-relapsed, proteasome inhibitor-relapsed patients, and patients who received prior carfilzomib therapy (expansion cohort, 31 patients).

Median time from multiple myeloma diagnosis was 4.9 years, with a range of 1.5 to 18.8 years. Median number of prior regimens was six, with a range of two to 18; 76% of patients were refractory to their last therapy.

At the last data cut-off on November 29, 2012, the patients had received a median of two cycles (1 to 11 cycles), and five patients remained on treatment.

Adverse effects (AEs) of grade 3 or less were seen in 83% of patients. In 52% of patients, there were common drug-related AEs of grade 3 or less, including thrombocytopenia (33%), diarrhea, neutropenia (17%), decreased appetite, fatigue, and lymphopenia (8%). Six patients had drug-related parenteral nutrition. Five patients stopped therapy due to AEs, and one patient died on study due to an unrelated AE.

Weekly oral MLN9708 was generally well-tolerated and showed activity in this heavily pretreated population who had prior exposure to immunomodulatory drugs and bortezomib.

________________________________________

Kumar S, Bensinger W, Zimmerman TM, et al. Weekly MLN9708, an investigational oral proteasome inhibitor, in relapsed/refractory multiple myeloma: results from a phase I study after full enrollment. J Clin Oncol. 2013;(suppl; abstr 8514).