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Karyopharm (KPTI) To Present Updated Phase IIb STORM And Phase Ib STOMP Clinical Data At The American Society of Hematology 2016 Annual Meeting



11/3/2016 8:39:03 AM

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- Diverse Data Continue to Reinforce the Efficacy and Safety of Selinexor in Patients with Heavily Pretreated Refractory Multiple Myeloma -

- Twenty-one Abstracts Selected, Including Nine Oral Presentations -

NEWTON, Mass., Nov. 03, 2016 (GLOBE NEWSWIRE) -- Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, today announced that 21 abstracts have been selected for presentation, including 9 oral presentations, at the American Society of Hematology (ASH) 2016 annual meeting being held December 3-6, 2016 in San Diego.  Two key abstracts being presented at the meeting will feature updated data from Karyopharm’s Phase 2b STORM and Phase 1b/2 STOMP studies, which are evaluating selinexor (KPT-330), the Company’s lead, novel, oral Selective Inhibitor of Nuclear Export (SINE™) compound, for the treatment of patients with multiple myeloma (MM). Selinexor has demonstrated robust and durable responses with favorable safety profiles in both studies and these data will be updated for presentation at the meeting.

“The STORM and STOMP studies continue to demonstrate robust response rates, with selinexor showing tolerability, both as a single-agent and in combination with other widely used therapies in heavily pretreated patients with MM,” said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. “Collectively, the MM data being presented at ASH this year continue to support the efficacy and safety of oral selinexor, as well as our planned development path in MM, and we look forward to presenting even more mature data at the meeting in December.”

Updated Phase 2b STORM Clinical Data

In an oral presentation titled, “Selinexor and Low Dose Dexamethasone in Patients with Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib and Anti-CD38 Ab Refractory MM STORM Study,” Dan T. Vogl, MD, MSCE, Assistant Professor of Medicine, Perelman School of Medicine, University of Pennsylvania, will present updated clinical data from the ongoing Phase 2b STORM study, a single-arm clinical trial evaluating selinexor in combination with low-dose dexamethasone in heavily pretreated patients with quad-refractory or penta-refractory disease. Patients with quad-refractory disease have documented evidence that they have previously received two PIs (bortezomib (Velcade®) and carfilzomib (Kyprolis®)) and two IMiDs (lenalidomide (Revlimid®) and pomalidomide (Pomalyst®)), and their disease is refractory to at least one PI, at least one IMiD, and has progressed following their most recent therapy.  Patients with penta-refractory myeloma have quad-refractory disease that is also refractory to an anti-CD38 monoclonal antibody, such as daratumumab (Darzalex™) or isatuximab.

Phase 2b STORM Efficacy as of September 6, 2016
CategoryN1ORR (%)CBR (%)VGPR (%)PR (%)MR (%)SD (%)PD (%)NE (%)
Overall7816 (21%)25 (32%)4 (5%)12 (15%)9 (12%)27 (35%)9 (12%)17 (22%)
Quad24810 (21%)14 (29%)2 (4%)8 (17%)4 (8%)21 (44%)4 (8%)9 (19%)
Penta3306 (20%)11 (37%)2 (7%)4 (13%)5 (17%)6 (20%)5 (17%)8 (27%)
1One patient not included, did not have active myelomaORR=Objective Response Rate (VGPR+PR)
2The majority of these patients (40 of 48) received 6 doses per cycle CBR=Clinical Benefit Rate (VGPR+PR+MR)
3The majority of these patients (19 of 30) received 8 doses per cycleVGPR=Very Good Partial Response
 PR=Partial Response
 MR=Minor Response
 SD=Stable Disease
 PD=Progressive Disease
 NE=Non Evaluable
  

All responses were adjudicated by an Independent Review Committee (IRC).  Among the 78 evaluable patients (median seven prior treatment regimens) at September 6, 2016, the overall response rate (ORR) was 21%, and included very good partial responses (VGPR) and partial responses (PR).  Among the 48 patients in the quad-refractory group, the ORR was 21%. For comparison, in a similar quad-refractory patient population, Darzalex had an ORR of 21% and isatuximab had an ORR of 20%.  Among the 30 patients in the penta-refractory group, the ORR was 20%.  Clinical benefit rate (ORR + MR) was 32% (all patients), 29% (quad-refractory), and 37% (penta-refractory).  Median overall survival (OS) was 9.3 months for all patients, greater than 11 months (median not reached) for responders (=PR), and 5.7 months for non-responders.  Median duration of response (DOR) was approximately 5 months.  The progression free survival (PFS) in this heavily pretreated population was 2.1 months. Grade =3 cytopenias were the most common side effects and were generally not associated with clinical sequellae. There were low rates of Grade =3 non-hematologic toxicities, with no new safety signals identified.  In particular, there was one reported case of Grade =4 infection (1.3%) and there was one reported case of sepsis (1.3%).

Dr. Vogl said, “Patients with penta-refractory myeloma are no longer responding to any of our most effective myeloma agents. This is a growing population for whom we currently have no specific therapy, representing an unmet need.   To my knowledge, selinexor is the first agent to show durable activity in this difficult-to-treat population.  The results are particularly intriguing because the response rate to oral selinexor is comparable to that achieved with daratumumab or isatuximab.  In addition, the overall survival seen in patients responding to selinexor is better than one would expect in this very refractory population. We look forward to further elucidating the potential benefits of selinexor in the STORM trial expansion, which will include approximately 120 additional patients with penta-refractory disease.”

To Karyopharm's knowledge, no agent has previously shown activity in patients with penta-refractory MM. As a result, the Company has expanded the STORM study to include approximately 120 additional patients with penta-refractory MM and expects to report top-line data from the expanded cohort in early 2018.  Assuming a positive outcome, Karyopharm intends to use the data from the expanded STORM study to support a request that the FDA consider granting accelerated approval for selinexor in MM.

Updated Phase 1b STOMP Clinical Data

In an oral presentation titled, “Selinexor in Combination with Bortezomib and Dexamethasone Demonstrates Significant Activity in Patients with Refractory Multiple Myeloma Including Proteasome-Inhibitor Refractory Patients,” Nizar Bahlis, MD, Associate Professor of Hematology, Southern Alberta Cancer Research Institute, will present updated clinical data from the selinexor + Velcade (bortezomib) + dexamethasone (SVd) arm of the ongoing Phase 1b/2 STOMP study in heavily pretreated relapsed/refractory MM patients.

A summary of data from all 22 patients receiving selinexor in combination with Velcade and dexamethasone in the dose-escalation portion of the study treated as of July 25, 2016 is outlined in the following table and described below.

Phase 1b STOMP Study (Selinexor + Velcade (Bortezomib) + Dexamethasone Arm) as of July 25, 2016
Prior PI StatusNORR (%)CR (%)VGPR (%)PR (%)MR (%)SD (%)PD (%)CBR (%)
Refractory
(7 Bortezomib, 3 Carfilzomib, 2 Ixazomib)
127 (58%)1 (9%)--6 (50%)3 (25%)1 (68%)1 (68%)10 (83%)
Not Refractory (Exposed or Naïve) 1010 (100%)--5 (50%)5 (50%)------10 (100%)
All2217 (77%)1 (5%)5 (23%)11 (50%)3 (14%)1 (5%)1 (5%)20 (91%)
ORR=Overall Response Rate (CR+VGPR+PR), CR=Complete Response, VGPR=Very Good Partial Response, PR=Partial Response, MR=Minor Response, SD=Stable Disease, PD=Progressive Disease

Of the 22 patients enrolled in the SVd combination arm (median of four prior treatment regimens), 17 responded (1 patient with a complete response (CR), five patients with a very good partial response (VGPR) and 11 patients with a partial response (PR)) for an overall response rate (ORR) of 77%.  An additional three patients achieved a minor response (MR), for a clinical benefit rate (CBR) of 91%.  Only one patient had progressive disease.  All 10 patients with non-refractory disease responded (5 patients with a VGPR and 5 patients with a PR) for an ORR and CBR of 100%.  Twelve of the 22 patients in the SVd combination arm had MM previously refractory to a proteasome inhibitor and some patients had high-risk cytogenetics including deletion of chromosome 17p.  Seven of these 12 patients responded (1 CR and 6 PR) for an ORR of 58%.  An additional three patients achieved a MR for a CBR of 83% in this subgroup. Of note, the expected ORR for bortezomib-dexamethasone combination in patients with myeloma that is not refractory to a proteasome inhibitor is approximately 50%, and the ORR for those with refractory disease would be less than 10%.

The most commonly reported adverse events were fatigue, anorexia, nausea and diarrhea, which were primarily grade 1 or 2 and reversible. Four grade 3 and two grade 4 incidences of thrombocytopenia (without bleeding) were also reported.  There was one reported case of grade 1 peripheral neuropathy in the selinexor (80 mg bi-weekly) cohort. 

“We continue to be impressed with the high level of durable activity of selinexor in combination with bortezomib, especially in patients whose disease is already refractory to proteasome inhibitors,” said Dr. Bahlis.  “The tolerability profile of the combination was quite favorable with low rates of neuropathy and cytopenias, particularly in this heavily pretreated population. Selinexor appears to have one of the most potent synergistic effects with bortezomib reported to date.”

Based on the robust data from the SVd arm of the Phase 1b portion of the STOMP study, the Company plans to initiate a pivotal, randomized Phase 3 study, known as the BOSTON (Bortezomib, Selinexor and dexamethasone) study, which will evaluate SVd at the recommended dose compared to bortezomib and low-dose dexamethasone (Vd) in patients with MM who have had one to three prior lines of therapy.  Karyopharm has identified the combination dose of selinexor (100mg weekly), bortezomib (1.3 mg/m2 weekly given sub-cutaneously for 4 of 5 weeks) and dexamethasone (40mg weekly) to be used in the BOSTON study.  The study will be conducted worldwide and will enroll approximately 360 patients.  Based on feedback from the FDA, the protocol is currently being finalized and the Company remains on track to commence the BOSTON study in early 2017.

Dr. Bahlis continued, “To our knowledge, this is the only Phase 3 study evaluating a triple combination therapy incorporating once-weekly Velcade.  We anticipate that this regimen will continue to show reduced rates of cytopenias, neuropathy and gastrointestinal side effects based on the continuing STOMP results.  From a patient convenience as well as a health economic perspective, these data are very exciting because the combination of oral selinexor and bortezomib requires fewer doses and fewer hospital visits, making this treatment regimen much more patient friendly, and potentially more cost effective than currently established therapies.”

In addition to these updated data from the STORM and STOMP studies, other key multiple myeloma abstracts selected for presentation at ASH include an oral presentation describing a Phase 1 study evaluating the combination of selinexor with proteasome inhibitor Kyprolis (carfilzomib) and dexamethasone in relapsed/refractory MM (Andrzej Jakubowiak, University of Chicago; Pub ID 973) and a poster presentation describing data from the selinexor + Pomalyst (pomalidomide) + dexamethasone arm of the Phase 1b dose-escalation portion of the STOMP study, also in patients with relapsed/refractory MM (Christine Chen, Princess Margaret Hospital; Pub ID 3330).

Karyopharm to Host Multiple Myeloma-focused Dinner Reception and Webcast at ASH 2016

On Monday, December 5, 2016, Karyopharm will host an investor and analyst dinner reception, which will feature a moderated panel discussion with recognized thought leaders in the treatment of MM, updated selinexor data in MM, and a live Q&A session.  The event will take place during the ASH 2016 annual meeting and interested parties can access a live webcast of the event beginning Monday, December 5, 2016 at 8:15 p.m. PT by going to the “Investors” section of the company's website at http://investors.karyopharm.com/events.cfm.

Oral and Poster Presentations Highlighting Selinexor in Acute Myeloid Leukemia (AML)

Several other key abstracts focused on the investigation of selinexor for the treatment of AML were selected for presentation at ASH, including two oral and two poster presentations.  The first oral presentation describes updated data from the Phase 2 SAIL study evaluating the combination of selinexor, with Ara-C and Idarubicin in patients with relapsed/refractory AML (Walter Fiedler, University Medical Center Hamburg; Pub ID 341) and the second oral presentation highlights data from a clinical trial evaluating the combination of selinexor with high-dose cytarabine and mitoxantrone in patients with AML (Amy Wang, University of Chicago; Pub ID 212).  The two poster presentations (Bhavana Bhatnagar, Ohio State University; Pub ID 1651 and Kendra Sweet, Moffitt Cancer Center, Tampa FL; Pub ID 4040) highlight early-stage clinical data demonstrating the feasibility and tolerability of selinexor in combination with other standard of care agents in patients with AML, including in elderly patients, as well as early signs of clinical activity, including response rates that are superior to historical data.

Details for the full list of ASH presentations are as follows:

Oral presentations

Title:  Selinexor and Low Dose Dexamethasone in Patients with Lenalidomide, Pomalidomide, Bortezomib, Carfilzomib and Anti-CD38 Ab Refractory MM STORM Study
Presenter:  Dan Vogl, Abramson Cancer Center, University of Pennsylvania
Publication ID:  491
Session:  653. Myeloma: Therapy, excluding Transplantation: New Agents for Multiple Myeloma; Sunday, December 4, 2016; 4:30-6:00 PM PT
Location:  San Diego Convention Center, Hall AB
Date and Time:  Sunday, December 4, 2016 at 5:30 PM PT

Title:  Selinexor in Combination with Bortezomib and Dexamethasone Demonstrates Significant Activity in Patients with Refractory MM Including Proteasome-Inhibitor Refractory Patients
Presenter:  Nizar Bahlis, Southern Alberta Cancer Research Institute, University of Calgary
Publication ID:  977
Session: 653. Myeloma: Therapy, excluding Transplantation: Novel Approaches; Monday, December 5, 2016; 2:45-4:15 PM PT
Location:  Manchester Grand Hyatt San Diego, Seaport Ballroom BC
Date and Time:  Monday, December 5, 2016; 3:45 PM PT

Title:  Final Results of Phase 1 MMRC Trial of Selinexor, Carfilzomib, and Dexamethasone in Relapsed/Refractory MM
Presenter:  Andrzej Jakubowiak, University of Chicago
Publication ID:  973
Session:  653. Myeloma: Therapy, excluding Transplantation: Novel Approaches; Monday, December 5, 2016; 2:45-4:15 PM PT
Location:  Manchester Grand Hyatt San Diego, Seaport Ballroom BC
Date and Time:  Monday, December 5, 2016; 2:45 PM PT

Title:  Phase II Results of Ara-C and Idarubicin in Combination with the Selective Inhibitor of Nuclear Export Compound Selinexor in Patients with Relapsed or Refractory AML
Presenter:  Walter Fiedler, University Medical Center Hamburg, Hamburg, Germany
Publication ID:  341
Session:  613. Acute Myeloid Leukemia: Clinical Studies: Optimizing Current AML Therapy; Sunday, December 4, 2016; 9:30-11:00 AM PT


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