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TOURMALINE-MM4 trial of ixazomib maintenance meets primary endpoint

Nov 13, 2019

TOURMALINE-MM4 is a phase III study designed to compare single-agent ixazomib maintenance to placebo in patients with newly diagnosed multiple myeloma (NDMM) who were not treated with a stem cell transplant (SCT). On the 7 thNovember 2019 it was announced that the TOURMALINE-MM4 trial had met its primary endpoint of prolonging progression-free survival (PFS) compared to placebo. 1 

TOURMALINE-MM4 ( NCT02312258) 1,2

  • Phase III, randomized, placebo-controlled, double-blind study in adult patients with NDMM who were not treated with SCT (N= 706) 1
    • Patients had received 6­–12 months of initial therapy 1
    • Patients must have achieved a partial response or better to this initial therapy 1
  • Trial arms: single-agent ixazomib versusplacebo 1
    • Ixazomib (3mg, or placebo capsule) was orally administered on Day 1, 8, and 15 of each 28-day cycle for up to 26 cycles 2
    • Dose reductions were permitted if a patient experienced an adverse event associated with the study drug (3mg, 2.3mg, 1.5mg, and discontinuation) 2
  • Primary endpoint: PFS
    • Defined as time from date of randomization to date of first documented disease progression or death from any cause, as per independent review committee evaluation 2
  • Secondary endpoints include: overall survival, time to progression, and percentage of patients converting from minimal residual disease (MRD)-positive to MRD-negative responses 2
  • This is the first phase III study to use a maintenance therapy that was not part of the initial induction therapy 1

Results 1

  • Efficacy:
    • The study met its primary endpoint of prolonging PFS compared to placebo
  • Safety:
    • The safety profile of ixazomib in the maintenance setting was consistent with that reported of single-agent use, with no new safety signals
  • The pharmaceutical company responsible for the trial are expecting to submit the full data results for presentation at an upcoming meeting 1

Context 1

There are several ongoing TOURMALINE trials investigating ixazomib as monotherapy or ixazomib in combination with other agents in different multiple myeloma (MM) patient populations. 1The TOURMALINE-MM1 study is comparing ixazomib + lenalidomide + dexamethasone (Ixa-Rd) to placebo + Rd in patients with relapsed/refractory MM, whilst the TOURMALINE-MM3 trial is comparing ixazomib to placebo as maintenance in patients with NDMM following induction and autologous SCT. The results of the TOURMALINE-MM3 study were presented at the American Society of Hematology (ASH) meeting, 2018, and are available here. 3

  1. BusinessWire. Phase 3 Trial of NINLAROTM (ixazomib) as First Line Maintenance Therapy Met Primary Endpoint in Multiple Myeloma Patients not treated with Stem Cell Transplantation.[Accessed 2019 Nov 08]
  2. A Study of Oral Ixazomib Maintenance Therapy in Participants With Newly Diagnosed Multiple Myeloma (NDMM) Not Treated With Stem Cell Transplantation (SCT).[Accessed 2019 Nov 08]
  3. Dimopoulos M.A. et al., Maintenance Therapy with the Oral Proteasome Inhibitor (PI) Ixazomib Significantly Prolongs Progression-Free Survival (PFS) Following Autologous Stem Cell Transplantation (ASCT) in Patients with Newly Diagnosed Multiple Myeloma (NDMM): Phase 3 Tourmaline-MM3 Trial; 2018 Dec 2. Oral Abstract #301: ASH 60th Annual Meeting and Exposition, San Diego, CA