Ninlaro Prolongs Progression-free Survival in Multiple Myeloma Patients Not Given ASCT, Phase 3 Trial Shows

First-line maintenance therapy with Ninlaro (ixazomib) prolongs the time without disease progression in adults with multiple myeloma not treated with an autologous stem cell transplant, meeting its primary goal, data from a Phase 3 trial show.

Ninlaro is an oral proteasome inhibitor marketed by Takeda. Proteasome inhibitors block the activity of a cellular complex that breaks down unnecessary or faulty proteins, called proteasome. By interfering with proteasome activity, these therapies are intended to prevent cancer cells from destroying this toxic buildup of proteins, which ultimately kills cancer cells.

Ninlaro is currently the only proteasome inhibitor approved to be used in combination with Revlimid (lenalidomide) and dexamethasone in previously treated people with multiple myeloma. Revlimid is available as a maintenance therapy for multiple myeloma patients in the U.S. and Europe. However, it has only been approved for those who underwent an autologous stem cell transplant (ASCT).

In an autologous transplant, stem cells are collected, stored and then infused back into the patient after intensive therapy.

The multicenter and double-blind Phase 3 TOURMALINE-MM4 trial (NCT02312258; sponsored by Takeda) is assessing the effects of Ninlaro as a first-line maintenance therapy for people with newly diagnosed multiple myeloma who did not undergo an ASCT.

TOURMALINE-MM4 is the first industry-sponsored Phase 3 trial to explore maintenance therapies not used as an initial induction treatment but a “switch” therapy in this patient group, Takeda reported in a press release.

The study enrolled 706 patients, who were randomly assigned to either a 3 mg or 4 mg capsule of Ninlaro or a placebo, both administered orally on days 1, 8 and 15 of each 28-day cycle, for up to 26 cycles. All had completed six to 12 months of initial therapy, and achieved a partial response or better.

The trial’s primary endpoint, or goal, was to assess progression-free survival, or the time patients lived without disease worsening. Secondary goals included overall survival and safety assessments.

Results showed that treatment with Ninlaro prolonged the time patients lived without signs of disease progression compared to the placebo. No further details were available.

Ninlaro’s safety profile in the maintenance setting was also seen to be consistent with findings from previous studies analyzing the medication when administered alone. No new safety concerns were reported, according to the release.

Takeda is planning to present full TOURMALINE-MM4 data at an upcoming medical meeting.

“We are very encouraged by the results of the TOURMALINE-MM4 trial and continue our forward momentum in developing maintenance options for multiple myeloma patients. Importantly, this is the third positive Phase 3 readout from the TOURMALINE clinical trial program,” said Phil Rowlands, PhD, head of the Oncology Therapeutic Area Unit at Takeda.

“We remain committed to bringing this convenient and well-tolerated treatment option to patients,” Rowlands added.

The company is conducting three other trials within its TOURMALINE program. TOURMALINE-MM1 (NCT01564537) is investigating Ninlaro in combination with Revlimid and dexamethasone in relapsed or refractory multiple myeloma, TOURMALINE-MM2 (NCT01850524) is assessing a similar combination but in people with newly diagnosed multiple myeloma, and TOURMALINE-MM3 (NCT02181413) is testing maintenance treatment with Ninlaro in patients with newly diagnosed multiple myeloma following induction therapy and an ASCT.