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Karyopharm Announces Dosing of First Patients in Two New Company-Sponsored Clinical Studies in Melanoma and Myelofibrosis Pharma & Healthcare Monitor Worldwide Karyopharm Announces Dosing of First Patients in Two New Company-Sponsored Clinical Studies in Melanoma and MyelofibrosisKaryopharm Therapeutics Inc. (NASDAQ: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced dosing of the first patients in two new company-sponsored Phase 2 and 1/2 clinical studies evaluating XPOVIO (selinexor), the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound in combination with approved therapies in patients with advanced melanoma and in patients with treatment nave myelofibrosis. These company-sponsored studies follow encouraging results from preclinical research and earlier stage, investigator-sponsored clinical studies conducted by Karyopharm's scientific collaborators. "Despite recent advances in treatment options for both metastatic melanoma and myelofibrosis, far too many patients either do not respond or have short-lived responses to currently available treatment options, making the development of novel drug treatment approaches incredibly important for these diseases," said Sharon Shacham, PhD, MBA, Chief Scientific Officer of Karyopharm. "Substantial need remains for continued research into new druggable targets and identifying multiple targets and pathways that have the potential to be inhibited synergistically using combination approaches. We believe XPOVIO's oral administration, along with its novel mechanism of action, make it a promising treatment candidate for new, single and synergistic combination regimens across both hematologic and solid tumors." Summary of Newly Initiated Clinical Studies: A Phase 2 Study Evaluating XPOVIO in Combination with Keytruda (pembrolizumab) in Recurrent Advanced Melanoma This Phase 2, multicenter, open-label study (XPORT-MEL-033; NCT04768881) will evaluate the safety and efficacy of XPOVIO in combination with Keytruda and is expected to enroll approximately 40 patients with locally advanced or metastatic melanoma that is resistant to initial checkpoint inhibitor therapy. Patients will receive once-weekly oral XPOVIO (80mg) and Keytruda (400mg intravenously once every six weeks) until disease progression, toxicity or withdrawal from the study, whichever occurs first. The primary endpoint of the study is overall response rate (ORR). Secondary endpoints include safety, progression-free survival, overall survival (OS), and complete response rate, among several others. Preclinical studies have shown that XPOVIO selectively kills malignant melanoma cells and synergistically increases the antitumor activity of check point inhibitors1,2,3. Two early clinical studies, one investigating XPOVIO as a single agent4 and one investigating XPOVIO plus Keytruda5, in heavily pretreated advanced melanoma, have shown that this activity is borne out in clinical studies. A Phase 1/2 Study Evaluating XPOVIO in Combination with Jakafi (ruxolitinib) in Treatment Nave Myelofibrosis This global Phase 1/2, multicenter, open-label study (XPORT-MF-034; NCT04562389) will evaluate the safety and efficacy of XPOVIO in combination with Jakafi and is expected to enroll approximately 237 patients with treatment nave myelofibrosis. The study will be conducted in two phases: Phase 1a/1b and Phase 2. The Phase 1a dose escalation portion of the study will determine the maximum tolerated dose and the recommended Phase 2 dose (RP2D) and will evaluate safety and preliminary efficacy. The Phase 1b dose expansion portion of the study will be conducted at the determined RP2D and will further assess the safety and preliminary efficacy at this dose level. In the Phase 2 portion of the study, patients will be randomized 1:1 to receive either once weekly XPOVIO plus Jakafi (15mg or 20mg twice daily) or Jakafi (15mg or 20mg twice daily) monotherapy. The primary endpoint for the Phase 2 portion of the study is the percentage of patients who achieve spleen volume reduction of at least 35% from baseline. Secondary endpoints for the Phase 2 portion of the study include safety, percentage of patients who achieve total symptom score reduction of ?50%, OS, anemia response and ORR, among several others. This new Phase 1/2 study is supported by multiple preclinical data sets which showed that (i) nuclear cytoplasmic transport is essential for survival of JAK2V617F-mutant HEL cells in vitro, a major vulnerability and a potential therapeutic target in MF6, (ii) that XPOVIO significantly reduced white blood cells (WBCs), granulocytes and spleen GFP+ cells in in vivo models of JAK2V617F-driven myeloproliferative neoplasms, and (iii) the combination of XPOVIO and ruxolitinib in vivo showed significant reduction in WBCs, granulocytes, spleen GFP+ cells, as well as in spleen weight when compared to either agent alone7. Collectively, these data support the clinical investigation of XPOVIO combined with ruxolitinib in patients with myelofibrosis. 2021 Global Data Point. |
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