Phase 3 SEAL Study Meets Primary End Point in Patients with Unresectable Dedifferentiated Liposarcoma

The randomized, double-blind, placebo-controlled, cross-over, phase 3 SEAL (Selinexor in Advanced Liposarcoma) study evaluating single agent, oral selinexor (Xpovio) versus matching placebo in patients with advanced unresectable dedifferentiated liposarcoma met its primary end point of a statistically significant increase in progression-free survival (HR, 0.70; P = .023), according to Karyoparhm Therapeutics.

The phase 2/3, randomized, double blind, placebo controlled, multicenter study (NCT02606461) is designed to assess the efficacy and safety of a twice weekly, 60 mg fixed dose of selinexor in patients with advanced unresectable dedifferentiated liposarcoma following at least 2 prior therapies.

The phase 2 portion of the study enrolled approximately 57 patients and randomized them 1:1 to treatment; the phase 3 portion enrolled approximately 285 patients and randomized them 2:1.

Notably, the trial allowed patients on placebo with objective progression to cross over to the selinexor treatment arm. Of those who received selinexor, there was a trend towards an improvement in the median overall survival compared to patients who started the trial on the placebo arm of the study and never crossed over to the selinexor treatment arm.

Regarding safety, the safety profile for selinexor was consistent with previous clinical studies with fewer hematologic and infectious adverse events as compared to studies of selinexor in patients with multiple myeloma and diffuse large B-cell lymphoma (DLBCL).

Detailed results from the SEAL study will be presented virtually in an oral presentation at the Connective Tissue Oncology Society (CTOS) Annual Meeting on November 20, 2020.

"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. "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.”

“We look forward to presenting the detailed results at the upcoming CTOS Annual Meeting and plan to submit a New Drug Application to the U.S. Food and Drug Administration in the first quarter of 2021 requesting the approval of [selinexor] to treat the patient population studied in SEAL,” Shacham added. “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."

Currently, selinexor is approved by the FDA as a treatment for patients with relapsed or refractory multiple myeloma and relapsed or refractory DLBCL. The agent is currently the only XPO1 inhibitor approved by the FDA and has been tested in clinical trials across a variety of cancer indications worldwide since 2012.

Karyopharm has also submitted a supplemental new drug application (sNDA) for selinexor that is currently under review by the FDA for the expansion of the agent's label to include selinexor as a treatment for patients with multiple myeloma after at least 1 prior line of therapy. Under the prescription drug user fee act (PDUFA), the FDA assigned the sNDA an action date of March 19, 2021.

Reference:

Karyopharm Announces Phase 3 SEAL Study Meets Primary Endpoint with Significant Increase in Progression-Free Survival in Patients with Unresectable Dedifferentiated Liposarcoma [news release]. Newton, Massachusetts. Published November 2, 2020. Accessed November 3, 2020. https://investors.karyopharm.com/2020-11-02-Karyopharm-Announces-Phase-3-SEAL-Study-Meets-Primary-Endpoint-with-Significant-Increase-in-Progression-Free-Survival-in-Patients-with-Unresectable-Dedifferentiated-Liposarcoma