SENTRY (NCT04562389), a pivotal Phase 3 trial, is a randomized, double-blind, placebo-controlled trial of 60 mg selinexor in combination with ruxolitinib in frontline myelofibrosis (MF) (n=353), versus ruxolitinib monotherapy. Conducted by Karyopharm Therapeutics, Inc., in collaboration with the Menarini Group, SENTRY was designed to evaluate two co-primary endpoints: spleen volume reduction of 35% or more (SVR35) and absolute total symptom score (Abs-TSS).

The trial met the first co-primary endpoint, demonstrating that patients who were treated with the combination of selinexor plus ruxolitinib achieved a clear and statistically significant improvement in SVR35, compared to patients who received ruxolitinib alone. These results highlight that the combination arm enabled rapid, deep and sustained spleen volume reductions.

"Achievement of spleen reduction is the essential goal of myelofibrosis treatment. Importantly, the spleen reduction results seen in SENTRY were rapid, deep and durable, and associated with potential overall survival benefit for the patients receiving the combination," said Dr. Claire Harrison, Professor of Myeloproliferative Neoplasms and Deputy Chief Medical Officer at Guy's and St. Thomas' NHS Foundation Trust. "We are encouraged that these results represent a potential new therapeutic advance for our patients who are in dire need of better options."

Other key highlights include:

• Absolute Total Symptom Score (Abs-TSS): The combination arm demonstrated a comparable benefit to ruxolitinib alone, with a 9.9 point improvement in Abs-TSS at week 24, in patients who received the combination, compared to a 10.9 point improvement in patients who received ruxolitinib alone. The difference across the two arms was not statistically significant, and the combination arm did not meet this second co-primary endpoint.
• Overall Survival (OS): While these data were immature at the time of analysis, a promising early OS signal, a pre-specified secondary endpoint, was observed with the selinexor combination compared to ruxolitinib alone. The study showed a greater than 50% reduction in the risk of death for patients receiving the selinexor combination (HR 0.43).
• Spleen Volume Reduction: Consistent SVR35 benefit was observed across prespecified subgroups. Notably, at week 24, superior spleen volume reduction was achieved by the selinexor combination, regardless of the ruxolitinib dose, including by patients receiving less than 15 mg of ruxolitinib per day.
• Variant Allele Frequency (VAF) Reduction: This pre-specified exploratory endpoint, which is associated with SVR35, was observed in 32% of patients in the selinexor plus ruxolitinib arm at week 24 versus 23.9% of patients treated with ruxolitinib alone, indicating the combination's potential for disease modification.
• Safety and Tolerability: The combination demonstrated a manageable safety and tolerability profile consistent with the known profile of selinexor and ruxolitinib individually. No new safety signals were observed.

"The strength of the spleen response and the encouraging early overall survival data observed in the SENTRY study creates hope for a potential new treatment option for patients suffering from this devastating disease with dismal outcomes," said Elcin Barker Ergun, CEO of the Menarini Group. "Our dedication and commitment to bring transformational treatments to patients facing cancer is stronger than ever."

About Myelofibrosis (MF)

Myelofibrosis (MF) is a type of blood cancer that belongs to a group of diseases called Myeloproliferative Neoplasms (MPNs). These diseases are caused by the overgrowth of abnormal blood-forming cells in the bone marrow, which leads to the formation of scar tissue. This scarring makes it difficult for the body to produce healthy blood cells. The incidence of MF is rare, with only about one or two people diagnosed each year for every 100,000 individuals, and the median survival after diagnosis is six years. Additionally, for people living with MF, their quality of life can be compromised by symptoms including fatigue, an enlarged spleen, and low blood counts, all of which are caused by the disease. ^1,2,3

To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at [email protected]. All of the relevant information can be found at https://stemline.com/contact/

Please see Summary of Product Characteristics (SmPC) and European Public Assessment Report at www.ec.europa.eu.

Please refer to local prescribing information where selinexor is approved for full information. Menarini Group holds licensing rights for selinexor and currently markets it in numerous European countries and global territories. In the U.S., Karyopharm Therapeutics markets selinexor and the full prescribing information is available here.

About The Menarini Group

The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of $5.5 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini's products are available in 140 countries worldwide. For further information, please visit www.menarini.com.