Targeting Aurora A gene could halt rhabdoid tumor growth in children

October 04, 2017

Phase 1 Dose-Escalation Study of Investigational Agent MLN9708, An Oral Proteasome Inhibitor, in Patients with Relapsed or Refractory Multiple MyelomaThe interim data from this ongoing study were collected from 35 relapsed/refractory multiple myeloma patients, all of whom had received at least two prior therapies, which must have included VELCADE, lenalidomide or thalidomide, and corticosteroids.

Of the 26 patients in the dose-escalation cohorts, 15 were refractory to VELCADE; of the 15 patients in the expansion cohorts, seven were refractory to VELCADE. The results, presented by Paul Richardson, M.D., Dana Farber Cancer Institute, Boston, Mass., showed:

Maximum tolerated dose was established as 2.0 mg/m2 Dose-limiting toxicities (DLT) of grade 3 rash and grade 4 thrombocytopenia were seen at 2.23 mg/m2 The preliminary tumor response data showed two partial responses, one at 1.2 mg/m2 and the second at 2.23 mg/m2. The patient at 1.2 mg/m2 remains on treatment at cycle 12; the patient 2.23 mg/m2 has received 10 cycles and remains on-study 17 patients had stable disease Response evaluation is ongoing The most common adverse events of any grade reported in more than 20 percent of patients were fatigue, diarrhea, upper respiratory infection, nausea, thrombocytopenia, cough, dyspnea, pyrexia and vomiting The most common grade 3/4 adverse events were thrombocytopenia (23 percent), neutropenia (8 percent) and non-cardiac chest pain (8 percent) No drug-related grade 2 or higher peripheral neuropathy was reported

Adults with relapsed/refractory MM after at least two prior therapies, which must have included bortezomib, thalidomide/lenalidomide, and corticosteroids, received oral MLN9708 on Days 1, 4, 8 and 11 every 21 days. Starting dose was 0.24 mg/m2, escalated using a 3+3 scheme based on dose-limiting toxicities in cycle 1. Toxicity was graded by NCI-CTCAE v3. Response was assessed by modified EBMT criteria.

Source: Millennium: The Takeda Oncology Company