"We are highly encouraged by the promising, durable activity and safety we continue to observe in the STOMP trial," said
In the poster, titled "A Phase 1b/2 Study of Selinexor in Combination with Backbone Therapies for Treatment of Relapsed/Refractory Multiple Myeloma," Dr. Nizar Bahlis of the
Dr. Bahlis commented, "We are particularly impressed with the high level of durable activity of selinexor in combination with bortezomib, particularly in patients whose disease is refractory to proteasome inhibitors. In addition, the preliminary results show that selinexor can combine with pomalidomide with good tolerability and strong responses. Together, these data indicate that selinexor can be added to standard treatments for patients with myeloma with high rates of anti-tumor activity, consistent with preclinical results showing that selinexor can reverse resistance to other therapies."
A summary of data from the first 24 patients treated as of
| Best Responses* Arms SdB, SdP, SdL as of |
|||||||||
| Treatment Arm | N | ORR (%) | CR (%) | VGPR (%) | PR (%) | MR (%) | SD (%) | PD (%) | CBR (%) |
| SdB - All Patients1 |
16 | 11 (69%) | 1 (6%) | 3 (19%) | 7 (44%) | 3 (19%) | 1 (6%) | 1 (6%) | 14 (88%) |
| SdB - Proteasome Inhibitor Refractory2 |
10 | 7 (70%) | 1 (10%) | 1 (10%) | 5 (50%) | 1 (10%) | 1 (10%) | 1 (10%) | 8 (80%) |
| SdP3,4 | 7 | 4 (57%) | -- | 1 (14%) | 3 (43%) | 1 (14%) | 2 (29%) | -- | 5 (71%) |
| SdL5 | 1 | 1 (100%) | -- | -- | 1 (100%) | -- | -- | -- | 1 (100%) |
*Responses were adjudicated according to the
1Includes 3 patients on treatment with unconfirmed VGPRs, 5 patients on treatment with unconfirmed PRs
2Seven out of 10 patients who have responded on the SdB Arm have either bortezomib & carfilzomib-refractory (N=2), bortezomib-refractory (N=7), or carfilzomib-refractory (N=1) MM
3Includes 2 patients on treatment with unconfirmed PRs
4All responders have lenalidomide-refractory MM
5Includes 1 patient on treatment with an unconfirmed PR
- Of the 16 evaluable patients treated in the SdB combination arm, 11 responded (1 patient with a complete response (CR), 3 patients with a very good partial response (VGPR) and 7 patients with a partial response (PR)) for an overall response rate (ORR) of 69%. An additional 3 patients achieved a minor response (MR), for a clinical benefit rate (CBR) of 88%. Ten of the 16 evaluable patients in the SdB combination arm had MM previously refractory to a proteasome inhibitor and several had high risk haplotypes including deletion of chromosome 17p. Seven of these 10 patients responded (1 CR, 1 VGPR and 5 PR) for an ORR of 70%. An additional patient achieved a MR for a CBR of 80% in this subgroup. Overall, side effects were similar to, or less than, those observed with single-agent selinexor. In the SdB arm, the most commonly reported adverse events were fatigue, anorexia, nausea and diarrhea, which were primarily grade 1 or 2. Four grade 3 and two grade 4 incidences of thrombocytopenia (without bleeding) were also reported. Peripheral neuropathy has not been reported.
- Of the 7 evaluable patients treated in the SdP combination arm, 4 responded for an ORR of 57%, including 1 VGPR and 3 PR. An additional patient had an MR, for a CBR of 71%. Commonly reported adverse events for patients enrolled in this arm were nausea and dysgeusia, which were primarily grade 1 or 2, grade 3 thrombocytopenia without bleeding (2 patients), and three grade 3 and one grade 4 incidences of neutropenia without infection.
- In addition, the 1 evaluable patient treated in the SdL combination arm achieved a PR.
- Across all arms, the most common adverse events were anorexia, nausea, fatigue and thrombocytopenia, which were similar to, or lower than, those historically observed with selinexor or backbone therapies separately. Of the 24 patients evaluable for response, 63% remained on therapy for over 3 months and many are continuing treatment.
Second Generation SINE™ Compound KPT-8602
Two e-posters describing promising preclinical activity of KPT-8602, Karyopharm's second-generation SINE™ compound, in both acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL) were also presented:
- In the first e-poster, titled "KPT-8602 is a Second-Generation XPO1 Inhibitor with Improved In Vivo Tolerability and Potent In Vivo Activity Against Acute Lymphoblastic Leukemia," Dr.
Jolien De Bie of the Katholieke Universiteit Leuven, described effects of KPT-8602 on ALL cell lines, including inhibition of XPO1-cargo interaction and XPO1-dependent nuclear export. In addition, potent anti-leukemic cytotoxicity and prolonged survival was observed in animal models treated with KPT-8602 compared to vehicle control.
- The second e-poster, titled "KPT-8602, a Second Generation Clinical Stage Selective Inhibitor of Nuclear Export (SINE) Compound Shows Enhanced Anti-Tumor Activity when Combined with Venetoclax or Bendamustine in DLBCL," Dr.
Erkan Baloglu of Karyopharm, described the preclinical activity of KPT-8602 as a single-agent and in combination with bendamustine or venetoclax in models of DLBCL, including aggressive double hit DLBCL.
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 (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. Over 1,500 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 is being evaluated in several later-phase clinical trials, including one in older patients with acute myeloid leukemia (SOPRA), one in patients with diffuse large B-cell lymphoma (SADAL), one in patients with liposarcoma (SEAL) and a single-arm trial of selinexor and low-dose dexamethasone in patients with multiple myeloma (STORM). Additional Phase 1 and Phase 2 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform the company's clinical development priorities for selinexor. The latest clinical trial information for selinexor is available at www.clinicaltrials.gov.
About KPT-8602
KPT-8602 is a second-generation oral SINE™ compound. KPT-8602 functions by binding to and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. KPT-8602 has demonstrated minimal brain penetration in animals, which has been associated with reduced toxicities in preclinical studies while maintaining potent anti-tumor effects.
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 the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, including the timing of initiation of certain trials and of the reporting of data from such trials. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the company's current expectations. For example, there can be no guarantee that any of Karyopharm's SINE™ compounds, including selinexor (KPT-330) and KPT-8602, or any other drug candidate that Karyopharm is developing will successfully complete necessary preclinical and 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
Contact:Justin Renz (617) 658-0574 jrenz@karyopharm.comGina Nugent (617) 460-3579 nugentcomm@aol.com
Source: Karyopharm Therapeutics
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