General MM

TOURMALINE-MM4 trial of ixazomib maintenance meets primary endpoint

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 7th November 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 therapy1
    • Patients must have achieved a partial response or better to this initial therapy1
  • Trial arms: single-agent ixazomib versus placebo1
    • Ixazomib (3mg, or placebo capsule) was orally administered on Day 1, 8, and 15 of each 28-day cycle for up to 26 cycles2
    • 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 evaluation2
  • Secondary endpoints include: overall survival, time to progression, and percentage of patients converting from minimal residual disease (MRD)-positive to MRD-negative responses2
  • This is the first phase III study to use a maintenance therapy that was not part of the initial induction therapy1
Results1
  • 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 meeting1
Context1

There are several ongoing TOURMALINE trials investigating ixazomib as monotherapy or ixazomib in combination with other agents in different multiple myeloma (MM) patient populations.1 The 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

References
  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. https://www.businesswire.com/news/home/20191107005221/en/Phase-3-Trial-NINLAROTM-ixazomib-Line-Maintenance [Accessed 2019 Nov 08]
  2. ClinicalTrials.gov. A Study of Oral Ixazomib Maintenance Therapy in Participants With Newly Diagnosed Multiple Myeloma (NDMM) Not Treated With Stem Cell Transplantation (SCT). https://clinicaltrials.gov/ct2/show/NCT02312258 [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
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