Phase 3 Trial Stops Testing Idasanutlin in AML Patients Undergoing Chemo

Phase 3 Trial Stops Testing Idasanutlin in AML Patients Undergoing Chemo

Roche has removed idasanutlin (RG7388), an investigational anti-cancer agent, from its Phase 3 MIRROS trial that was assessing the effectiveness of the medication when used in combination with chemotherapy in patients with relapsed or refractory acute myeloid leukemia.

The decision was made when MIRROS (NCT02545283) failed to meet its primary goal of showing the combination therapy of idasanutlin and cytarabine was superior to placebo plus cytarabine at prolonging patients’ survival in the first quarter of 2020.

As a result, the company also halted its plans to request the approval of the combination therapy for this indication, which was planned to take place this year, had the study been successful. 

Idasanutlin is an oral, selective, small-molecule antagonist of MDM2, a protein that normally binds and blocks the activity of the tumor-suppressor protein p53. By preventing MDM2 from interacting with p53, idasanutlin was expected to increase the stability of p53, which in turn would activate signaling cascades that limit the growth and eventually lead to the destruction of cancer cells.

Another Phase 1b/2 trial (NCT02670044) is currently investigating the safety, tolerability, and preliminary efficacy of idasanutlin in combination with Venclexta (venetoclax) in patients with relapsed or refractory AML who are not eligible for chemotherapy.

The trial, which is expected to enroll around 166 participants, is currently recruiting patients at several clinical sites across the U.S., Canada, France, and Italy. More information about trial contacts and recruiting sites can be found here.

Venclexta, marketed and developed by Genentech and AbbVie, has been approved by the U.S. Food and Drug Administration (FDA) to treat different types of cancer, including AML in older patients who are not eligible for standard chemotherapy.

The medication is a potent selective inhibitor of the B-cell lymphoma-2 (BCL-2) protein, which normally prevents cancer cells from being destroyed. By preventing cancer cells from over-producing this protein, Venclexta primes them for programmed cell death (apoptosis).

Because idasanutlin indirectly promotes the degradation of MCL1 — another protein that also inhibits apoptosis and is a known resistance factor to BCL-2 inhibition — there is the possibility that the combination therapy of idasanutlin and Venclexta may be more successful at treating patients with relapsed or refractory AML.

Also ongoing is a Phase 1b/2 trial (NCT03850535) evaluating the safety, efficacy, and pharmacological properties of idasanutlin when given alongside cytarabine and daunorubicin to treat newly-diagnosed AML patients.

The study is currently recruiting participants in the U.S., E.U., and Australia, and is expected to enroll around 80 patients. Top-line findings are expected in March 2021.

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