Takeda studies MLN9708 as multiple myeloma treatment

Takeda has analysed the safety, tolerability and maximum tolerated dose of MLN9708, which is being tested as a treatment for multiple myeoma (MM).

The ongoing study reviewed MLN9708 in 60 MM patients who had received two or more therapies beforehand, with primary objectives including the safety, tolerability and MTD of MLN9708 when taken once a week.

Of patients who had received a median of four therapies, 85 per cent, 97 per cent, 53 per cent and 15 per cent had obtained prior VELCADE (bortezomib), lenalidomide, thailidomide and carflzomib/marizomib respectively.

Some 72 per cent of patients were refractory to their last therapy, with the MTD being determined at 2.97mg on a weekly dosing schedule, but three patients were affected by dose limiting toxicities, while one patient at 3.95mg was affected by grade 3 nausea, vomiting and diarrhea and one patient was hit by grade 3 erythema multiforme rash.

One patient at 2.97mg experienced grade 3 nausea, vomiting and diarrhea, with all three of them continuing the study at a lower dose.

Among 50 evaluable patients, an overall response rate of 18 per cent was found, including one very good partial response and eight partial responses.

Throughout all cohorts, the most common drug-related adverse events of any grade were thrombocytopenia (43 percent), diarrhea and nausea (38 percent), fatigue (37 percent), vomiting (35 percent), decreased appetite (25 percent) neutropenia (22 percent) and peripheral neuropathy (20 percent).

MLN9708 is an investigational oral, proteasome inhibitor, which is being assessed in multiple myeloma and other malignancies. It is also the first oral proteasome inhibitor to reach the clinical trial phase.

Three Phase 3 trials are now ongoing. TOURMALINE-MM1 is investigating MLN9708 in combination with lenalidomide and dexamethasone in relapsed and/or refractory MM, while TOURMALINE-MM2 is looking at MLN9708 when mixed with lenalidomide and dexamethasone in patients with newly diagnosed MM.

The third trial, TOURMALINE-AL1, is focussing on MLN9708 plus dexamethasone in people who have relapsed or refractory light chain amyloidosis.

Posted by Fiona Griffiths