“Preliminary data from the Kyprolis arm of the Phase 1b/2 STOMP study show early but encouraging clinical activity, including two patients who achieved a complete response, along with an expected and manageable tolerability profile, in patients with heavily pretreated, double-refractory Kyprolis-naïve multiple myeloma,” said
New Phase 1b/2 STOMP Study Data: Selinexor plus Kyprolis and Low-dose Dexamethasone (SKd)
In this arm of the Phase 1b/2 STOMP study, oral selinexor (dosed once weekly) is being evaluated in combination with Kyprolis (56mg/m2 or 70mg/m2 once weekly) and low dose dex (orally, 40mg once weekly or 20mg twice weekly) in patients with relapsed refractory MM who have received at least two prior therapies, which can include previous treatment with a proteasome inhibitor (PI), one or more immunomodulatory drugs (IMiDs: Revlimid, Pomalyst) or Darzalex. All patients on the study had previously received both PIs and IMiDs. The following table is a summary of the efficacy results:
| Best Responses1 in Evaluable SKd Patients as of 1-May-20192 | |||||
| Category | N | ORR | CR | VGPR | SD |
| All (Kyprolis-naïve) | 9 | 7 (78%) | 2 (22%) | 5 (56%) | 2 (22%) |
Key: ORR=Overall Response Rate (CR+VGPR+PR); SD= Stable Disease
1 Responses were adjudicated according to the
2 Based on interim unaudited data
Among the 9 patients evaluated for safety as of the data cutoff date, the most common treatment-related AEs were cytopenias, along with gastrointestinal and constitutional symptoms; most were manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (67%), fatigue (44%), hyperglycemia (44%), anorexia (33%) and vomiting (33%), and were mostly Grade 1 and 2 events. As expected, the most common treatment-related Grade 3 and 4 AEs were hematologic AEs and included thrombocytopenia (78%), leukopenia (33%), anemia (22%) and neutropenia (22%). Dose limiting toxicities, including Grades 3 and 4 thrombocytopenia, Grade 3 pneumonia and Grade 3 vomiting, were observed in patients receiving selinexor 80mg and Kyprolis 70mg/m2 and selinexor 100mg and Kyprolis 56mg/m2. No DLTs were reported in the selinexor 80mg and Kyprolis 56mg/m2 cohort, and therefore, confirmation of the recommended Phase 2 dose (RP2D) is ongoing with this dosing regimen.
Updates on Phase 1b/2 STOMP Study: SDd and SPd
Selinexor plus Darzalex and Low-dose Dexamethasone (SDd)
In this arm of the Phase 1b/2 STOMP study, oral selinexor (dose escalated using either 100mg once weekly or 60mg twice weekly) is being evaluated in combination with Darzalex (16mg/kg intravenously once weekly) and low dose dexamethasone (dex; orally, 40mg once weekly or 20mg twice weekly) in patients with relapsed or refractory MM who received at least three prior lines of therapy, including a PI and an IMiD, or patients with MM refractory to both a PI and an IMiD. The following table is a summary of the updated efficacy results:
| Best Responses1 in Evaluable SDd Patients as of 1-May-20192 | ||||
| Category | N3 | ORR | VGPR | PR4 |
| Darzalex naïve | 30 | 22 (73%) | 11 (37%) | 11 (37%) |
| All | 32 | 22 (69%) | 11 (34%) | 11 (34%) |
Key: ORR=Overall Response Rate (VGPR+PR); PR= Partial Response
1 Responses were adjudicated according to the
2 Based on interim unaudited data
3 Two patients were not evaluable for response as they withdrew consent prior to disease follow up
4 Two unconfirmed PRs
Despite the heavily pretreated nature of the patients in the study, with 100% of the patients having dual- (PI and IMID)-refractory disease, only one patient (3%) did not have at least a minimal response. Median progression-free survival (PFS) has not been reached. Among patients with at least a PR, the median time on treatment was 7.7 months, while the median time on study for all evaluable patients was 4.8 months. Median time to response was 1.0 month. Based on published data, the expected ORR for Darzalex therapy without selinexor in the Darzalex-naïve population is ~29%. Thus, the ORR of 73% continues to provide a basis for further evaluation of the SDd combination.
Among the 31 patients evaluated for safety as of the data cutoff date, the most common treatment-related AEs were cytopenias, along with gastrointestinal and constitutional symptoms; most manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (68%), fatigue (58%), anorexia (32%), insomnia (32%), diarrhea (32%), hyponatremia (32%), and vomiting (26%), and were mostly Grade 1 and 2 events. As expected, the most common Grade 3 and 4 treatment-related AEs were hematologic AEs and included thrombocytopenia (42%), anemia (29%), leukopenia (26%) and neutropenia (23%). No Grade 5 AEs were reported. Based on these tolerability and efficacy data, the recommended RP2D of SDd is selinexor (100mg orally, once weekly), Darzalex (16mg/kg, once weekly) and dex (40mg orally, once weekly).
Selinexor plus Pomalyst and Low-dose Dexamethasone (SPd)
In this arm of the Phase 1b/2 STOMP study, oral selinexor (60mg or 80mg once weekly or 60mg or 80mg twice weekly) is being evaluated in combination with Pomalyst (2mg, 3mg or 4mg orally, once daily) and low dose dex (orally, 40mg once weekly or 20mg twice weekly) in patients with relapsed or refractory MM who received at least two prior lines of therapy, including a PI and an IMiD, or patients with MM refractory to both a PI and an IMiD. The following table is a summary of the efficacy results:
| Best Responses1 in Evaluable SPd Patients as of 1-May-20192 | |||||
| Prior Therapy Status | N3 | ORR | VGPR | PR4 | Median PFS |
| Pomalyst-naïve and Revlimid refractory or relapsed | 30 | 17 (57%) | 7 (23%) | 10 (33%) | 12.2 months |
| Pomalyst and Revlimid refractory | 10 | 3 (30%) | - | 3 (30%) | 4.2 months |
| All | 40 | 20 (50%) | 7 (18%) | 13 (33%) | 10.4 months |
Key: ORR=Overall Response Rate (VGPR+PR)
1 Responses were adjudicated according to the
2 Based on interim unaudited data
3 Five patients not evaluable for response: one death unrelated to myeloma, one non-compliance with study procedures, two withdrawal of consent before disease follow up, one patient on treatment pending response evaluation
4 One unconfirmed PR
Among the 45 patients evaluated for safety as of the data cutoff date, the most common treatment-related AEs were cytopenias, along with gastrointestinal and constitutional symptoms; most manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (56%), fatigue (53%) and anorexia (49%) and mostly Grade 1 and 2 events. As expected, the most common treatment-related Grade 3 and 4 AEs were hematologic AEs and included neutropenia (56%), thrombocytopenia (31%), anemia (31%) and leukopenia (16%). There were three Grade 5 treatment-related events (febrile neutropenia, intracranial hemorrhage and pneumonia). Determination of the RP2D is still ongoing.
Details for the EHA 2019 STOMP presentations are as follows:
Oral Presentation
Title: Safety and Efficacy of combination of Selinexor, Daratumumab, and Dexamethasone (SDd) in Patients with Multiple Myeloma (MM) Previously Exposed to Proteasome Inhibitors and Immunomodulatory Drugs
Lead author:
Abstract #: S1606
Session: Myeloma and other monoclonal gammopathies – Clinical
Date and Time:
Location: Auditorium
Poster Presentations
Title: Selinexor, Pomalidomide, and Dexamethasone (SPd) in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)
Lead author:
Abstract #: PF587
Session: Myeloma and other monoclonal gammopathies – Clinical
Date and Time:
Location: Poster Area
Title:A Phase 1b/2 Study of Selinexor, Carfilzomib, and Dexamethasone (SKd) in Relapsed/ Refractory Multiple Myeloma (RRMM)
Lead author:
Abstract #: PS1414
Session: Myeloma and other monoclonal gammopathies – Clinical
Date and Time:
Location: Poster Area
Additional selinexor presentations at EHA 2019 are as follows:
Title:A Phase 2 Study of Selinexor Plus Cytarabine and Idarubicin in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML)
Lead author:
Abstract #: S880
Session: Acute myeloid leukemia – Clinical
Date and Time:
Location: Elicium 2
Title: A Randomized, Open-Label, Phase II Study of Selinexor Versus Physician’s Choice (PC) In Older Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)
Lead author:
Abstract #: PF261
Session: Acute myeloid leukemia – Clinical
Date and Time:
Location: Poster Area
Note: As reported previously by Karyopharm in 2017, this study did not meet its pre-specified primary endpoint.
About Selinexor
Selinexor 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 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. In 2018, Karyopharm reported positive data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with triple class refractory multiple myeloma who have been previously exposed to all five of the most commonly prescribed anti-myeloma therapies currently available. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in the STORM study. Karyopharm's New Drug Application (NDA) seeking accelerated approval has been accepted for filing and granted Priority Review by the
About
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding our expectations relating to submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the anticipated timing of such submissions and actions, and the potential availability of accelerated approval pathways, the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor, and the plans for commercialization. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that regulators will agree that selinexor qualifies for accelerated approval in the U.S. or conditional approval in the E.U. as a result of our clinical data, including the data from the STORM study or the SADAL study in patients with relapsed or refractory DLBCL, or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the
Velcade® is a registered trademark of
Revlimid® and Pomalyst® are registered trademarks of
Kyprolis® is a registered trademark of
Darzalex® is a registered trademark of
Contacts:
Investors:
857-297-2241 | ikarp@karyopharm.com
Media:
212-600-1902 | david.rosen@argotpartners.com
Source: Karyopharm Therapeutics Inc.