By Lizzy Smith | Posted - Sep 15th, 2015

 

 

 

 

The STORM Study, Selinexor & The Active Clinical Trials Using This Drug

Earlier this summer, Karyopharm Therapeutics Inc. announced the initiation of the STORM study (Selinexor Treatment of Refractory Myeloma). STORM is a multi-center, single-arm Phase 2 study of selinexor (KPT-330) in heavily-pretreated patients with quad-refractory multiple myeloma. Selinexor, the company's lead, novel, oral Selective Inhibitor of Nuclear Export / SINE™ compound, will be evaluated in combination with low-dose dexamethasone in multiple myeloma patients whose disease was refractory to treatment with bortezomib (Velcade), lenalidomide (Revlimid), carfilzomib (Kyprolis) and pomalidomide (Pomalyst). The first approximately 80 patients can participate at 30 sites, primarily in the United States. About 25% of the patients will also have received treatment with an anti-CD38 monoclonal antibody such as daratumumab. Depending on the results from this initial group, the trial may be expanded to include more patients. Data from an expanded trial may support an accelerated approval of selinexor in refractory multiple myeloma. Selinexor received orphan drug designation from the U.S. FDA and the European Medicines Agency (EMA) for multiple myeloma.

"We are very encouraged by the responses and durability demonstrated to-date with selinexor in combination with low-dose dexamethasone in patients with relapsed and refractory multiple myeloma and look forward to continuing to evaluate selinexor in this patient population," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "Despite the approvals of a variety of new agents, myeloma remains a fatal disease with nearly all patients relapsing after all available therapies. Selinexor has demonstrated promising durability and early signs of potential synergy with some of the approved anti-myeloma agents. We look forward to presenting the data from STORM in the near future."

This open-label, single-arm Phase 2 study of selinexor in combination with low-dose dexamethasone will evaluate the safety and efficacy of a fixed dose of selinexor (80 mg) plus low dose dexamethasone (20 mg). Each compound will be given orally twice weekly to approximately 80 patients with multiple myeloma with quad-refractory multiple myeloma. In addition, patients will have received alkylating agents and glucocorticoids, and their myeloma must be refractory to their most recent therapy. Overall response rate (ORR) is the primary endpoint of the study and this endpoint has served as the basis for accelerated approvals in multiple myeloma for other agents. STORM was designed based on data from Karyopharm's Phase 1 study of selinexor in combination with low dose dexamethasone in relapsed/refractory multiple myeloma. As of December 1, 2014, Phase 1/2 data from ten heavily pretreated myeloma patients (median of seven prior therapies), nine of whom were evaluable for response, demonstrated a 67% ORR (partial response or better) and an 89% clinical benefit rate (minimal response or better). The overall median duration of response, measuring time from response to progression, is approximately seven months. To learn more about this study and selinexor, click here. To learn more about clinical trials using this drug, click on SparkCures finder here. All the research has been done for you! (For this drug, there are currently two trials) For more information on drug-specific trials for myeloma patients, click here. Want more info? Below is the Selinexor Fact Sheet from the drug's manufacturer. Keep reading below:   Selinexor Fact Sheet - (SINE, Selective Inhibition of Nuclear Transport) Selinexor is a novel, first in class, orally administered, Selective Inhibitor of Nuclear Export, or SINE™, therapy. SINE compounds inhibit XPO1-mediated nuclear-cytoplasmic transport by blocking XPO1 cargo binding over a defined period of time. SINE compounds work through two previously untapped areas of cancer biology: • Activate tumor suppressor proteins by retaining them in the cell nucleus, where these proteins detect cancerous DNA changes and induce cancer cell death • Reduce levels of key cancer causing proteins such as c-myc and bcl-2, reducing the growth of the cancers About Selinexor Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE™ compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is believed to lead to the selective induction of apoptosis (cell death) in cancer cells, while largely sparing normal cells. Over 900 patients have been treated with selinexor in company- and investigator-sponsored Phase 1 and Phase 2 clinical trials in advanced hematologic malignancies and solid tumors. Selinexor, has demonstrated anti-cancer activity observed across both hematologic and solid tumor malignancies. Karyopharm has initiated several registration-directed clinical trials of selinexor. The STORM trial, intended to be registration directed, is a single-arm trial of selinexor in patients with multiple myeloma that was initiated in May 2015 and is currently enrolling patients in the US. Registration directed trials include the SOPRA trial in older patients with acute myeloid leukemia, the SADAL trial in patients with diffuse large B-cell lymphoma and the SIRRT trial in patients with Richter's transformation. Karyopharm is broadly exploring selinexor in combination with chemotherapy and targeted agents in a large number of cancers based on preclinical evidence of synergy. The latest clinical trial information for selinexor is available at www.clinicaltrials.gov Selinexor has received orphan drug designation for the treatment of multiple myeloma from the U.S. Food and Drug Administration (FDA) and from the European Medicines Agency (EMA). Selienxor has also received orphan designation from the FDA and EMA for AML and DLBCL. In addition the EMA has granted orphan designation for CLL/SLL (including Richter’s transformation). Orphan designation was created to encourage the development of drugs which may provide significant benefit to patients suffering from rare diseases Selinexor in Multiple Myeloma Data on Selinexor in multiple myeloma patients enrolled from a phase I study of the safety, pharmacokinetics and pharmacodynamics of escalating doses in patients with advanced hematological malignancies were presented at the ASH annual meeting in December, 2014. In the ongoing Phase 1 clinical trial, Selinexor in combination with low-dose dexamethasone demonstrated high rates of durable responses, including a 67% overall response rate (partial response or better) and an 89% clinical benefit rate (minimal response or better) in nine evaluable patients with heavily pre-treated and refractory multiple myeloma (one patient was not evaluable for response). Six of these patients remained on study for at least 16 weeks, including two for 28 and 43 weeks, respectively, who were still on study as of December 1, 2014. The overall median duration of response (DOR), which measures time from response to progression, was approximately 7 months. • Overall response rate of 67%, was reported with one stringent complete response (sCR, 11%) and five partial responses (PR, 56%), and a clinical benefit rate of 89% in nine patients with heavily pretreated and refractory multiple myeloma treated with Selinexor in combination with low-dose dexamethasone (Sel-Dex), each dosed twice weekly at 45mg/m2 and 20mg, respectively. • The Sel-Dex combination demonstrated reduction in nausea grades and very little weight loss compared with Selinexor alone. The most common Grade 1/2 adverse events were: nausea, fatigue, anorexia and vomiting. • The Sel-Dex combination was also associated with an increase in time on study relative to Selinexor alone, with 66% of these nine evaluable patients remaining on study for at least 16 weeks, including two for 28 and 43 weeks, respectively, who remained on study as of December 1, 2014. • During the dose evaluation part of the study, the 60 mg/m2 Selinexor dose was deemed intolerable in this heavily pretreated patient population. Selinexor 45 mg/m2 is the recommended future study dose. Karyopharm has transitioned to a “fixed dose” of 80 mg based on these results. Also presented at the ASH annual meeting were data from a phase 1/2 investigator sponsored study (IST) to evaluate tolerability and efficacy of the combination of Selinexor with the proteasome inhibitor carfilzomib (Kyprolis®) and low-dose dexamethasone (Car-Dex) being conducted by the University of Chicago. In the first three treated patients, all of whom have myeloma refractory to carfilzomib and dexamethasone, Selinexor-Car-Dex induced one very good partial response (VGPR) and two partial responses (PR) with good tolerability. Dose escalation in this Phase 1 clinical study is ongoing. In a related preclinical study conducted at the University of Chicago, Selinexor combined with carfilzomib induced both autophagy and apoptosis in multiple myeloma cell lines and patient samples, suggesting synergy through a combination-based priming effect. The combination had minimal effects on normal lymphocytes. The STORM Trial The STORM trial (Selinexor Treatment of Refractory Myeloma) is a multi-center, single-arm Phase 2 study of selinexor (KPT-330) in multiple myeloma patients who are refractory to IMID and proteasome inhibitor therapies. Selinexor, will be evaluated in combination with low-dose dexamethasone in multiple myeloma patients whose disease was refractory to treatment with bortezomib (Velcade®), lenalidomide (Revlimid®), carfilzomib (Kyprolis®) and pomalidomide (Pomalyst®). The first cohort will enroll approximately 80 patients at about 30 sites, primarily in the United States, with ~25% of the patients also having received treatment with an anti-CD38 monoclonal antibody such as daratumumab. Depending on the results from this initial cohort, the trial may be expanded to include additional patients. Data from an expanded trial may support the submission of an NDA to the FDA for accelerated approval of selinexor in refractory multiple myeloma. This open-label, single-arm Phase 2 study of selinexor in combination with low-dose dexamethasone will evaluate the safety and efficacy of a fixed dose of selinexor (80 mg) plus low dose dexamethasone (20 mg). Each compound will be given orally twice weekly to approximately 80 patients refractory to IMID and proteasome therapy. In addition, patients will have received alkylating agents and glucocorticoids, and their myeloma must be refractory to their most recent therapy. Overall response rate (ORR) is the primary endpoint of the study and this endpoint has served as the basis for accelerated approvals in multiple myeloma for other agents. STORM was designed based on data from Karyopharm's Phase 1 study of selinexor in combination with low dose dexamethasone in relapsed/refractory multiple myeloma. There are currently 11 activate sites in the US: Gabrail Karmanos Vanderbilt Mayo, MN Mayo, AZ Hackensack Moffit Columbia Indiana University NYU Washington University, St Louis An additional 13 sites are in process of IRB review plus three additional sites to submit to IRB. Karyopharm Therapeutics Karyopharm Therapeutics Inc. (Nasdaq:KPTI) is a clinical-stage pharmaceutical company focused on the discovery and development of novel first-in-class drugs directed against nuclear transport targets for the treatment of cancer and other major diseases. Karyopharm's SINE™ compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). In addition to single-agent activity against a variety of different human cancers, SINE™ compounds have also shown biological activity in models of cancer, inflammation, autoimmune disease, certain viruses, and wound-healing. Karyopharm was founded by Dr. Sharon Shacham and is located in Newton, Massachusetts. For more information, please visit www.karyopharm.com. For more information, you may also view a video at the company's web site by clicking .  

 
Lizzy Smith
About the Author

Lizzy Smith - Lizzy Smith was diagnosed with myeloma in 2012 at age 44. Within days, she left her job, ended her marriage, moved, and entered treatment. "To the extent I'm able, I want to prove that despite life's biggest challenges, it is possible to survive and come out stronger than ever," she says.

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