Takeda: Phase 2 Data On Maintenance With Single-Agent Investigational Ixazomib

(RTTNews) - Takeda Pharmaceutical Co Ltd (TKPHF, TKPYY) on Sunday announced results from an open-label, Phase 2 study evaluating the safety and efficacy of oral, single-agent ixazomib (MLN9708) as maintenance therapy in patients with multiple myeloma (MM) who had received ixazomib, lenalidomide and dexamethasone as induction therapy.

The data from this trial demonstrate the potential feasibility of single-agent ixazomib maintenance therapy following 12 cycles of ixazomib-lenalidomide-dexamethasone, with deepening responses and an acceptable tolerability profile. These data were presented today at the 56th American Society of Hematology (ASH) annual meeting in San Francisco, CA.

"These findings suggest that treatment with single-agent ixazomib, an investigational oral proteasome inhibitor, in the maintenance setting has the potential to extend depth of response for patients following induction therapy," said Shaji Kumar, MD, Mayo Clinic, Rochester, NY.

The primary objective of the Phase 2 component of the study was the percent of patients achieving a very good partial response (VGPR) or better (defined as complete response (CR) + VGPR).

Fifty patients were enrolled in the Phase 2 cohort and received ixazomib, lenalidomide and dexamethasone as induction therapy for up to twelve 28-day cycles. Transplant-eligible patients could discontinue from the study for autologous stem cell transplant (ASCT) after six cycles. For those patients continuing on to receive ixazomib maintenance, treatment could continue until disease progression or unacceptable toxicity.

All patients who received ixazomib maintenance therapy had responded to induction therapy. During induction, 29 patients discontinued study treatment, primarily to undergo autologous stem cell transplant (ASCT). Other reasons included AEs, patient withdrawal, disease progression, and unsatisfactory response, among other factors.

Twenty-one patients completed induction and progressed to the maintenance phase of the study, during which they received single-agent ixazomib for a median of 19 treatment cycles, with a median treatment duration of 29 months.

Best overall confirmed/unconfirmed study response rates and additional results for patients who underwent any maintenance therapy were reported as follows:

- CR or better was reached in 52 percent of patients and VGPR or better was reached in 71 percent of patients

- forty-eight percent of patients improved their response during maintenance , including two VGPR to near-CR, five VGPR to CR, one VGPR to sCR, and two CR to sCR.

- median PFS of patients entering maintenance has not been reached

- fifty-two percent of patients remained on ixazomib maintenance after data cut-off

- median time to first response (=PR) was 0.99 months (range 0.92-5.78) and median time to best response was 7.46 months (range 1.02-24.74). Mean ixazomib relative dose intensity was 95 percent and 89.5 percent in the induction and maintenance phases, respectively.

- all patients who received ixazomib maintenance were alive after follow-up of 25.1-33.9 months from study entry.

During the maintenance phase of the study with single-agent ixazomib, there were no discontinuations due to AEs and no on-study deaths. Drug-related grade 3 adverse events (AEs) were reported in 14 percent of patients during ixazomib maintenance therapy, and included one each hypokalemia, thrombocytopenia, and cataract as reported by the investigator. No grade 4 drug-related AEs were reported during maintenance.

Serious AEs were reported in 19 percent of patients during maintenance, including grade 3 acute myocardial infarction, grade 3 pneumonia, grade 3 orthostatic hypotension, and grade 2 ventricular extrasystoles; all were considered not related to treatment. Only two patients required an ixazomib dose reduction due to AEs (neuralgia, peripheral neuropathy).

All grade drug-related adverse events during maintenance included diarrhea, nausea, pain in extremity, anemia, skin and SC tissue disorders, headache, hypokalemia, and thrombocytopenia.