ORR up to 78%! Selinexor multiple combination therapies are bright in MM clinical

Selinexor is a pioneering, oral, selective nuclear output inhibitor (SINE) compound that binds and inhibits the functioning of the nucleo-output protein XPO1 (also known as CRM1), causing tumor suppressors to accumulate in the nucleus, which will restart and amplify their tumor inhibition function, causing selective apoptosis of cancer cells without significantly affecting normal cellsresults released this time show that selinexor different combination therapies showed strong efficacy in all types of recurrent/refractory MM patients, with a total remission rate (ORR) of 57%-78%The data released at the meeting, which were released on 1 May 2019, were evaluated in accordance with the ISOC standards, as follows:.SKd protocol: ORR 78%this group of patients who have received at least two treatments but have relapsed in the disease, are evaluating the efficacy and efficacy of selinexor (once a week or ally) combined Kyprolis (56mg/m2 or 70mg/m2, once a week) and low doses of dexamethasone (oral, 40mg or 220mg per week)The treatments previously received by the patient may include a protease inhibitor (PI), one or more immunomodulating drugs (IMiDs: Revlimid, Pomalyst) or Darzalex, all of whom have been treated with PI and IMiD, but none have received Kyprolis treatmentresults showed that of the 9 assessable patients, 7 were remission, ORR was 78%, of which 2 were completely relieved, 5 were very good patients, and 2 were stablesafety, the most common adverse events are platelet reduction, accompanied by gastrointestinal and systemic symptoms, and most patients can be treated with dose adjustment and/or standard supportive careDose-restricted toxicity (DLT) was observed in patients treated with selincer 80mg and Kypris 70mg/m2 and selincer 100mg and Kypris 56mg/m2, including stage3 and 4 platelet reduction, stage 3 pneumonia and level 3 vomitingDLT is not reported in the selincer 80mg and Kypris 56mg/m2 treatment queues, so the administration is being identified as the recommended Phase II dose (RP2d)SDd protocol: ORR 73%patients in this group who had previously received at least 3 treatments (including one PI and one IMiD) were recurrent or refractory MM patients, or MM patients who had difficulty treating both pi and one IMiD, but none of them received Darzalex treatmentThe group is evaluating oral selinexor (100 mg per week or 60 mg twice a week) combined with Darzalex (16 mg/kg, intravenous lyme once per week) and low doses of dexamethasone (oral, 40 mg once a week or 2 times a week 20 mg) for treatmenta total of 32 patients in this group, data cut-off, 2 cases before the disease follow-up withdrawal consent, 30 patients can assess the efficacy: 22 patients were remission, ORR 73%, of which 11 received very good partial relief, 11 cases of partial remissionAccording to the data published, the expected ORR based on the Darzalex (excluding selinexor) scheme was about 29% of patients with refractory MM who had not previously received Darzalex treatment, so the SDd scheme of up to 73% of the ORR data in this group provided the basis for further evaluation of the programsafety, the most common adverse events are platelet reduction, accompanied by gastrointestinal and systemic symptoms, and most patients can be treated with dose adjustment and/or standard supportive care Based on efficacy and tolerability data, the recommended Phase II dose SDd solution is: selinexor (100 mg, once a week orally) plus Darzalex (16 mg/kg, once a week) and low dose of dexamethasone (40 mg, once a week)  SPd protocol: ORR 57% this group of patients are evaluating oral selinex for MM who has previously received at least two treatments (including one PI and one IMiD) that have relapsed or is difficult to treat, or for MM patients who have had difficulty treating one PI and one IMiD Or (60mg or 80mg, once a week or 2 times a week) combined with Pomalyst (2mg, 3mg, 4mg, once daily orally) and low doses of dexamethasone (oral, once a week 40mg or 20mg per week) results showed that of the 30 MM patients who had not previously received Pomalyst treatment and had difficult treatment or recurrence of Revlimid, 17 were remission, or 57%, of which 7 received very good partial remission and 10 cases of partial remission The median progression-free lifetime (PFS) is 12.2 months Of the 10 patients in which Pomalyst and Revlimid were difficult to treat, 3 were partially remission, with a median PFS of 4.2 months For the entire group, the total mitigation rate was 50% and the median PFS was 10.4 months safety, the most common adverse events are platelet reduction, accompanied by gastrointestinal and systemic symptoms, and most patients can be treated with dose adjustment and/or standard supportive care Based on efficacy and tolerability data, the recommended Phase II dose SDd solution is: selinexor (100 mg, once a week orally) plus Darzalex (16 mg/kg, once a week) and low dose of dexamethasone (40 mg, once a week) currently, the application for a new drug for selinexor's treatment of multiple difficult MM is under fda priority review by the FDA and has been submitted for listing in the European Union In addition to MM, Karyopharm is evaluating the drug for a variety of other recurrent or incurable diseases, including diffuse large B-cell lymphoma, acute myeloid leukemia, endometrial cancer, and more Reference source: Karyopham Reports New and Updated Selinexor Combination Data from the Phase 1b/2 STOMP Study at the European Hematology Association 2019 Meeting