Takeda Announces Results from Phase 3 Clinical Trial Evaluating NINLARO (ixazomib) in Newly Diagnosed Multiple Myeloma

On Sep 10, 2020

Takeda Pharmaceutical Company Limited announced results from the Phase 3 TOURMALINE-MM2 trial evaluating the addition of NINLARO (ixazomib) to lenalidomide and dexamethasone versus lenalidomide and dexamethasone plus placebo in newly diagnosed multiple myeloma patients not eligible for autologous stem cell transplant. These data will be presented at the virtual scientific meeting of the Society of Hematologic Oncology (SOHO) on Wednesday, September 9, 2020 at 6:15 p.m. CT.

The study found the addition of NINLARO to lenalidomide and dexamethasone resulted in a 13.5 month increase in median progression-free survival (PFS) (35.3 months in the NINLARO arm, compared to 21.8 months in the placebo arm; hazard ratio [HR] 0.830; p=0.073). The trial did not meet the threshold for statistical significance and the primary endpoint of PFS was not met.

“There is a specific need in newly diagnosed multiple myeloma, given there are currently no approved all-oral, proteasome inhibitor-based treatment options,” said Thierry Facon, MD, Lille University Hospital, principal investigator and lead author of TOURMALINE-MM2. “Findings from the TOURMALINE-MM2 trial are important overall for this patient population as well as across multiple subgroups including patients with high-risk cytogenetics. We hope these data will help inform future research and further progress for the multiple myeloma community.”

Other endpoints presented include complete response (CR) rate, overall survival (OS) and median time to progression (TTP). The safety profile associated with NINLARO from the trial was generally consistent with the existing prescribing information.

“We hope the findings from the TOURMALINE-MM2 trial will encourage constructive conversations and help progress future research efforts, particularly for patients who could benefit from an all-oral, proteasome inhibitor-based combination that helps preserve quality of life,” said Christopher Arendt, Head, Oncology Therapeutic Area Unit, Takeda. “As a company, we remain committed to the multiple myeloma community and look forward to sharing mature data from our ongoing Phase 3 multiple myeloma maintenance studies in the future.”

Key findings to be presented by TOURMALINE-MM2 trial investigator, Shaji Kumar, MD, Mayo Clinic, include:

In the prespecified expanded high-risk cytogenetics subgroup, median PFS was 23.8 months in the NINLARO arm versus 18.0 months in the placebo arm (HR 0.690).
The rate of CR, a key secondary endpoint in the trial, was 26% in the NINLARO arm versus 14% in the placebo arm.
After a median follow up of 57.8 months in the NINLARO arm versus 58.6 months in the placebo arm for OS, the median OS was not reached in either arm (HR 0.998).
Median TTP was longer with the NINLARO combination versus placebo, at 45.8 months in the NINLARO arm versus 26.8 months in the placebo arm (HR 0.738).
Safety data include:
- Treatment emergent adverse events (TEAEs) were experienced by 96.6% of patients receiving NINLARO plus lenalidomide and dexamethasone compared to 92.6% of patients receiving placebo plus lenalidomide and dexamethasone.
- The most common TEAEs of clinical importance in the NINLARO arm were diarrhea, rash, peripheral edema, constipation and nausea.
- Grade ≥3 TEAEs were experienced by 88.1% of patients receiving NINLARO versus 81.4% receiving placebo.
- The majority of TEAEs were managed without discontinuation, with TEAEs resulting in 35% regimen discontinuation in the NINLARO arm and 26.9% in the placebo arm.
- The rate of on-study deaths was 7.6% in the NINLARO arm and 6.3% in the placebo arm.

“Insights from studies like TOURMALINE-MM2 are important, especially to those patients who may benefit from the convenience of treatment options that can be taken at home,” said Paul Giusti, President and Chief Executive Officer, Multiple Myeloma Research Foundation (MMRF). “These critical learnings enable the community to comprehensively assess the different treatment combinations available for patients and physicians.”

NINLARO is currently approved in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy in more than 65 countries. NINLARO is not approved as a treatment for newly diagnosed multiple myeloma.