Advancing Myelofibrosis Treatment: The Promise of the SENTRY Trial

The SENTRY trial represents a significant step forward in addressing the unmet needs of patients with myelofibrosis (MF), a rare and progressive blood cancer. Conducted by Karyopharm Therapeutics, this Phase 3 trial is designed to evaluate the efficacy of combining selinexor, a first-in-class XPO1 inhibitor, with the standard-of-care JAK inhibitor ruxolitinib in JAK inhibitor-naïve patients.

Why the SENTRY Trial Matters

Unmet Needs in Myelofibrosis Treatment

• Less than half of patients on approved JAK inhibitors achieve the benchmark of a 35% spleen volume reduction (SVR35), and many eventually stop responding.

• Myelofibrosis remains a challenging condition with limited treatment options for managing progressive symptoms and improving long-term outcomes.

Encouraging Phase 1 Results

Nearly 80% of patients treated with selinexor plus ruxolitinib achieved SVR35 compared to less than 50% with ruxolitinib alone.

Patients experienced an average improvement of 18.5 points in Absolute Total Symptom Score (Abs-TSS), a measure of symptom burden, compared to historical improvements of 11–14 points with JAK inhibitors alone.

Improved Trial Design

Following FDA feedback, the SENTRY trial now includes Abs-TSS as a co-primary endpoint, replacing the Total Symptom Score reduction (TSS50). Abs-TSS offers a more precise measure of cumulative symptom improvement over 24 weeks, aligning better with patient-centered outcomes.

The trial is actively enrolling  350 patients and aims to report top-line results in the second half of 2025.

What Sets Selinexor Apart

Selinexor works by inhibiting XPO1, a nuclear export protein involved in cancer cell survival. This mechanism complements the action of ruxolitinib, enhancing both symptom control and spleen volume reduction.

The combination therapy has demonstrated a favorable safety profile, with no new adverse signals in early trials.

Expert Perspectives

Dr. Raajit Rampal, Memorial Sloan Kettering Cancer Center, shares, “The doubling of SVR35 rates and the substantial improvements in Abs-TSS seen in the Phase 1 trial are meaningful and provide strong justification for the Phase 3 SENTRY trial.”

Another myelofibrosis expert weighs in on the recent clinical trial endpoint change: 

“The shift to Abs-TSS as a co-primary endpoint better represents the cumulative benefit patients experience, aligning with their treatment goals,”  says Dr. Ruben Mesa, Atrium Health Levine Cancer Institute.

Looking Ahead and Enrolling

The SENTRY trial holds promise for delivering a new standard of care for MF patients. By addressing both symptom burden and spleen size reduction with innovative combination therapy, the trial could transform outcomes and quality of life for this underserved patient population.

If you’re interested in enrolling in this clinical trial, click below to learn more: 

SENTRY Trial Enrollment

Sources: 

• Karyopharm Announces Favorable Change in Co-Primary Endpoint for Pivotal Phase 3 SENTRY Trial in Myelofibrosis - Oct 31, 2024