Takeda’s NINLARO fails to meet PFS primary endpoint in TOURMALINE-MM2 trial

Takeda Pharmaceutical said that the Phase 3 TOURMALINE-MM2 trial in newly diagnosed multiple myeloma patients for NINLARO (ixazomib) in addition to lenalidomide and dexamethasone failed to meet the primary endpoint of progression-free survival (PFS).

The late-stage trial assessed the combination of NINLARO (ixazomib) with lenalidomide and dexamethasone in comparison to lenalidomide and dexamethasone plus placebo in 705 patients, who are not eligible for autologous stem cell transplant.

Since 2015, NINLARO had secured approvals across various countries, including the US, in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who were subjected to at least one prior therapy. However, the oral proteasome inhibitor is yet to be approved as a treatment for newly diagnosed multiple myeloma.

The TOURMALINE-MM2 trial found that the addition of NINLARO to lenalidomide and dexamethasone delivered a 13.5 month increase in median PFS, 35.3 months in the NINLARO arm, compared to 21.8 months in the placebo arm. The clinical trial therefore did not meet the threshold for statistical significance.

Thierry Facon from Lille University Hospital, the principal investigator and lead author of the TOURMALINE-MM2 trial said: “There is a specific need in newly diagnosed multiple myeloma, given there are currently no approved all-oral, proteasome inhibitor-based treatment options.

“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.”

Takeda Pharmaceutical said that the median PFS in the prespecified expanded high-risk cytogenetics subgroup was 23.8 months in the NINLARO arm compared to 18.0 months recorded in the placebo arm.

The rate of complete response, which is a key secondary endpoint in the TOURMALINE-MM2 trial, was 26% in the NINLARO arm, while the same was 14% in the placebo arm.

As per the Japanese pharma giant, following a median follow up of 57.8 months in the NINLARO arm was recorded compared to 58.6 months in the placebo arm for overall survival. The company said that the median OS was not reached in both arms.

Takeda Pharmaceutical said that the safety profile associated with NINLARO from the late-stage trial was generally in line with the existing prescribing information.

Christopher Arendt – Takeda Pharmaceutical Oncology Therapeutic Area Unit Head said: “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.

“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.”