Selinexor Meets PFS Primary End Point in Phase 3 Study of Advanced Unresectable Dedifferentiated Liposarcoma

Selinexor (Xpovio) achieved the primary end point of progression-free survival (PFS) in the phase 3 SEAL study (NCT02606461) and induced a statistically significant reduction of approximately 30% in the risk of disease progression or death compared with placebo as treatment of patients with advanced unresectable dedifferentiated liposarcoma, according to the topline findings, Karyopharm Therapeutics, Inc., announced in a press release.

Selinexor led to a statistically significant increase in PFS compared with matching placebo (HR, 0.70; P =.023). These positive pivotal data indicate a major advance for the treatment of patients with liposarcoma, which demonstrates substantial potential for use of this XPO1 inhibitor for the treatment of other solid tumors.

"We are delighted to share these significant top-line results from the phase 3 portion of the SEAL study, the first, late-stage clinical data for selinexor in a solid tumor indication," said Sharon Shacham, PhD, MBA, president and chief scientific officer of Karyopharm, in a statement. "The top-line results from the SEAL study are particularly encouraging as advanced dedifferentiated liposarcoma represents a very difficult to treat cancer with no established standard of care and limited treatment options available to patients. Selinexor may be particularly promising as it represents the first oral therapy to show activity in patients with previously treated liposarcoma.”

Patients in the placebo arm were able to cross over to selinexor with objective progression, and among those that received the XPO1 inhibitor, a trend towards an improved median overall survival was observed compared with those in the placebo arm who did not cross over. The safety profile for selinexor was consistent with prior findings in clinical trials, with fewer hematologic and infectious adverse events observed compared with treatment in patients with multiple myeloma or diffuse large B-cell lymphoma.

SEAL, which stands for Selinexor in Advanced Liposarcoma, is a double-blind, placebo-controlled, multicenter phase 2/3 study, which was designed to evaluate the efficacy and safety of the twice-weekly fixed dose of selinexor at 60 mg. The phase 2 portion of the study included 57 patients who were randomized 1:1 to selinexor or placebo, and the phase 3 portion included 285 patients, who were randomized 2:1 to treatment.

The findings from this analysis will be presented virtually during an oral presentation at the Connective Tissue Oncology Society Annual Meeting, which will take place on November 20, 2020.

“We look forward to presenting the detailed results at the upcoming CTOS Annual Meeting and plan to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the first quarter of 2021 requesting the approval of selinexor to treat the patient population studied in SEAL,” stated Shacham. “If approved, selinexor would represent the first oral, non-chemotherapy agent available for patients with dedifferentiated liposarcoma. The encouraging data from the SEAL study also provide additional rationale for advancing the clinical development of selinexor in other solid tumor indications, including in endometrial, glioblastoma, lung, and other cancers where Karyopharm is currently conducting clinical studies."

The agent is currently approved as treatment of patients with relapsed/refractory multiple myeloma, as well as relapsed/refractory diffuse large B-cell lymphoma. Selinexor is the only XPO1 inhibitor approved by the FDA and has been tested extensively across a variety of cancer types globally since 2012.

A supplemental NDA has been submitted and is currently under review with the FDA for the expansion of the selinexor label to include patients with multiple myeloma after at least 1 prior line of therapy. The target action date for this application is March 19, 2021.

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_{Karyopharm Announces Phase 3 SEAL Study Meets Primary Endpoint with Significant Increase in Progression-Free Survival in Patients with Unresectable Dedifferentiated Liposarcoma. News Release. Karyopharm Therapeutics, Inc. November 2, 2020. Accessed November 3, 2020. https://bit.ly/2TQ30BC}