Assessing Selinexor/Ruxolitinib in JAKi Treatment-Naive Myelofibrosis

John Mascarenhas, MD, professor, medicine, Icahn School of Medicine, Mount Sinai, director, Center of Excellence for Blood Cancers and Myeloid Disorders, member, The Tisch Cancer Institute, Mount Sinai, discusses phase 3 of the SENTRY (NCT04562389) trial, a global, multicenter, phase 1/3 study evaluating the efficacy and safety of selinexor (Xpovio) when given in combination with ruxolitinib (Jakafi) in patients with JAK inhibitor treatment-naive myelofibrosis.

The study is being conducted in 2 phases. In phase 1, the open-label portion of the study, enrollment has been completed and the safety and recommended dose of selinexor plus ruxolitinib was studied. Phase 1a utilized a standard 3+3 design, and phase 1b was the dose-expansion part. Phase 3 of the trial is enrolling patients with JAK inhibitor treatment-naive myelofibrosis and randomizing them 2:1 to receive the combination therapy of selinexor with ruxolitinib or placebo with ruxolitinib.

In phase 3, the primary end points are the proportion of patients with spleen volume reduction of greater than or equal to 35% at week 24, and the proportion of patients with a total symptom score reduction of greater than or equal to 50% at week 24, as measured by the myelofibrosis symptom assessment form V4.0.

Transcription:

0:09 | The study we are talking about is a global, phase 3 study. It is a randomized, double-blind study evaluating the safety and efficacy of selinexor, which is an XPL1 inhibitor, in combination with ruxolitinib in JAK inhibitor-naive patients with myelofibrosis. We call this the SENTRY study. So it is really capitalizing on data that has already been generated, both as a single-agent in the relapsed/refractory setting, but also in combination with ruxolitinib in phase 2, demonstrating synergy of the 2 agents in terms of spleen reduction, symptom improvement, bone marrow fibrosis reduction, and a safety profile that would suggest that durability of response can be maintained.

0:54 | So this is now the natural evolution of this agent in myelofibrosis in a phase 3 study in patients who are JAK inhibitor-naive, comparing ruxolitinib, which is the standard of care, plus selinexor, the XPL1 inhibitor, vs ruxolitinib plus placebo.