Ninlaro Clinical Studies - Ixazomib Clinical Studies - Ninlaro


What have Ninlaro clinical trials shown?

Ninlaro® (ixazomib, Takeda Oncology) has been evaluated alone and in combination with other myeloma agents in both relapsed and/or refractory multiple myeloma and newly diagnosed disease.

Relapsed and/or Refractory Multiple Myeloma

The approval of Ninlaro was based on results from the Phase III TOURMALINE-MM1 trial, which included patients with relapsed and/or refractory multiple myeloma who had received one to three prior therapies. In this trial 722 patients received Ninlaro in combination with Revlimid® (lenalidomide, Celgene) and low-dose dexamethasone (IRd) or Revlimid-low-dose dexamethasone alone (Rd).

On average, patients receiving IRd lived significantly longer without their disease worsening compared to patients receiving Rd (20.6 months vs. 14.7 months).

  • Responses lasted longer when Ninlaro was added (20.5 months vs.15 months with Rd).
  • The overall response rate was higher with IRd compared with Rd (78% vs. 72%) and the complete response rate was also higher (12% and 7%, respectively).
  • Patients in this study continue to be followed for survival and safety outcomes.
  • IRd is listed as one of several preferred regimens for relapsed and/or refractory myeloma in current treatment guidelines.

In two Phase I trials, single-agent Ninlaro has been shown to provide clinical meaningful responses in patients with relapsed and/or refractory myeloma when given once or twice a week.

  • With weekly dosing, 27% of patients treated at the maximum tolerated dose achieved a partial response (PR). Patients in this study had received an average of 6 previous therapies and nearly three-quarters no longer responded to their last therapy.
  • Weekly dosing of Ninlaro appeared to be better tolerated than twice-weekly dosing.

In a small Phase II study in patients with relapsed myeloma, dexamethasone was shown to enhance the activity of weekly Ninlaro when added in instances where there was limited or lack of response to Ninlaro alone.

Based on the results of these early studies, Ninlaro alone or in combination with dexamethasone is listed as a preferred treatment option for relapsed and/or refractory in myeloma treatment guidelines.

Newly Diagnosed Multiple Myeloma

Ninlaro given weekly or twice-weekly has also been evaluated in combination with Revlimid-dex in Phase I/II trials in patients with newly diagnosed myeloma.

  • Results of the combination trial with weekly Ninlaro show a 92% overall response rate, with 58% of patients achieving a very good partial response rate or better, including a complete response (CR)/stringent CR rate of 27%.
    • The most common side effects were nausea, vomiting, rash, fatigue, and peripheral neuropathy.
    • Severe side effects were infrequent and the most common included rash, low white blood cell and platelet counts, gastrointestinal effects, and fatigue. There were few instances of severe peripheral neuropathy (6% of patients).
  • Following initial therapy with Ninlaro and Revlimid-dex, continuing maintenance therapy with Ninlaro alone was tolerable and improved responses and contributed to durable responses lasting over 2 years on average.
  • Preliminary results of a combination trial with Revlimid-dex and twice-weekly Ninlaro facilitated by the Multiple Myeloma Research Consortium (MMRC) also show a high overall response rate (95%), but higher rates of severe side effects and dose reductions were seen.
  • Ninlaro in combination with Revlimid-dex is listed as a treatment option for initial therapy in both transplant-eligible and -ineligible patients.

Ninlaro has also been evaluated in combination with cyclophosphamide and dexamethasone in a small Phase II trial in newly diagnosed patients who were not eligible for transplant.

  • Two doses of cyclophosphamide were evaluated (300 mg/m2 and 400 mg/m2).
  • The overall response rate in both dosing groups combined was 71%, including 9% complete responses.
  • Side effects, including serious adverse events, increased with the higher cyclophosphamide dose.

How is Ninlaro currently being studied in myeloma?

Ninlaro is being evaluated in clinical trials in the United States in relapsed and/or refractory myeloma, in newly diagnosed disease, and as maintenance therapy.

Ninlaro is being evaluated in several Phase III trials, including:

  • In combination with Revlimid-low-dose dex in an international clinical trial in patients with newly diagnosed myeloma (TOURMALINE-MM2) that has enrolled over 700 patients.
  • As maintenance therapy in patients who have achieved a partial response or better to their initial therapy and who have not undergone autologous stem cell transplantation (ASCT)
  • As maintenance therapy in patients who have achieved a partial response or better to their initial therapy and who have undergone ASCT, which has completed enrollment.

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