MedicalResearch.com Interview with:
Dr. Dixie-Lee Esseltine MD, FRCPC
Vice President, Oncology Clinical Research
MedicalResearch: What is Ixazomib?
Dr. Dixie-Lee Esseltine: Ixazomib is an investigational, oral, once-weekly proteasome inhibitor (PI) that is being investigated in multiple Phase 3 trials in multiple myeloma (MM) and systemic light-chain (AL) amyloidosis. It is the first oral proteasome inhibitor to enter Phase 3 clinical trials.
Proteasome inhibition is a mechanism underpinning an established standard of care in the treatment of multiple myeloma. However, the current biweekly parenteral administration of proteasome inhibitors may pose challenges to patients. The ability to demonstrate that an oral, once-weekly PI can extend PFS would be a remarkably important finding in the effort to address these challenges. Early studies suggest ixazomib, has activity in MM patients, both as a single agent in relapsed patients and in combination in frontline patients.
Ixazomib was granted orphan drug designation in multiple myeloma in both the U.S. and Europe in 2011, and for AL amyloidosis in both the U.S. and Europe in 2012. It was granted Breakthrough Therapy Designation for AL amyloidosis in the U.S. in 2014.
MedicalResearch: What is the design for this study?
Dr. Dixie-Lee Esseltine: The TOURMALINE MM-1 study (C16010) is a phase 3, randomized, double-blind study comparing ixazomib plus lenalidomide and dexamethasone versus placebo plus lenalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma. Patients were randomized to receive ixazomib 4.0mg days 1,8 and 15 or placebo with lenalidomide 25mg days 1-21 and dexamethasone 40mg days 1,8,15 and 22. Treatment was given every 28 days until disease progression or unacceptable toxicity. Evaluation was based on the International Myeloma Working Group (IMWG) Uniform Response Criteria.
MedicalResearch: What were the primary and secondary endpoints?
Dr. Dixie-Lee Esseltine: The primary endpoint was progression free survival (PFS). Key secondary endpoints included overall survival (OS) and OS in high risk patients with del (17) cytogenetics. Additional secondary endpoints included overall response rate (ORR), CR+VGPR response rate, duration of response (DOR), time to progression (TTP), safety, pain response rate, change in global health status, OS and progression free survival in high risk populations, PK data and association between response or resistance to ixazomib treatment and proteasome and NFKB-related genes.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Dixie-Lee Esseltine: Proteasome inhibition is a mechanism underpinning an established standard of care in the treatment of multiple myeloma; however, the current biweekly parenteral administration of proteasome inhibitors may pose challenges to patients. The ability to demonstrate that an oral, once-weekly Proteasome inhibition can extend progression free survival is a potentially important finding in the effort to address these challenges.
Taxeda Press Release:
Takeda Announces That the First Interim Analysis of the Phase 3 Study of Oral Ixazomib in Patients with Relapsed or Refractory Multiple Myeloma Met the Primary Endpoint of Improvement in Progression-Free Survival
Cambridge, Mass. and Osaka, Japan, February 10, 2015 – Takeda Pharmaceutical Company Limited (TSE:4502) today announced that the randomized, double-blind, placebo-controlled TOURMALINE-MM1 pivotal Phase 3 trial evaluating the safety and efficacy of ixazomib, the first oral proteasome inhibitor, conducted in patients with relapsed or refractory multiple myeloma (MM) achieved its primary endpoint of improving progression-free survival at the first pre-specified interim analysis. In the trial, patients treated with investigational ixazomib plus lenalidomide and dexamethasone lived without their disease worsening for a significantly longer time compared to patients who received placebo plus lenalidomide/dexamethasone.
Efficacy and safety data were reviewed by an Independent Data Monitoring Committee (IDMC). Takeda intends to submit these data to health authorities globally or marketing authorizations.
“We are very pleased with the outcome of this interim analysis of the pivotal trial, and are excited about the potential that investigational ixazomib holds for patients with multiple myeloma,” said Dixie-Lee Esseltine, MD, FRCPC, Vice President, Oncology Clinical Research, Takeda. “We thank the patients and investigators for their engagement and continued participation in this ongoing clinical evaluation of ixazomib.”
About the TOURMALINE-MM1 Study
The study (n=722) is an international, randomized, double-blind, placebo controlled clinical trial designed to compare the efficacy and safety of two treatment regimens administered until progression – ixazomib plus lenalidomide and dexamethasone versus placebo plus lenalidomide and dexamethasone – in adult patients with relapsed and/or refractory MM.2.
Subjects included in the study had a confirmed diagnosis of MM, received one to three prior therapies and meet other outlined eligibility criteria. Patients who were refractory to lenalidomide or proteasome inhibitor-based therapy were excluded.
Ixazomib (MLN9708) is an investigational oral proteasome inhibitor, which is being studied in multiple myeloma (MM), systemic light-chain (AL) amyloidosis and other malignancies. Ixazomib was granted orphan drug designation in MM in both the U.S. and Europe in 2011, and for AL amyloidosis in both the U.S. and Europe in 2012. Ixazomib received Breakthrough Therapy status by the U.S. Food and Drug Administration (FDA) for relapsed and/or refractory AL amyloidosis in 2014. It is also the first oral proteasome inhibitor to enter Phase 3 clinical trials. Four global Phase 3 trials are ongoing: TOURMALINE-MM1, investigating ixazomib vs. placebo in combination with lenalidomide and dexamethasone in relapsed and/or refractory MM; TOURMALINE-AL1, investigating ixazomib plus dexamethasone in patients with relapsed or refractory AL amyloidosis; TOURMALINE-MM2, investigating ixazomib vs. placebo in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM; and TOURMALINE-MM3, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant. For additional information on the ongoing Phase 3 studies please visit www.clinicaltrials.gov.
Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for people worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com.
MedicalResearch.com Interview with:, & Dr. Dixie-Lee Esseltine MD, FRCPC (2015). Phase 3 Study of Oral Proteasome Inhibitor For Relapsed or Refractory Multiple Myeloma MedicalResearch.com