Good day. My name is Chad, and I'll be your conference operator today. At this time, I would like to welcome everyone to Karyopharm Therapeutics phase III SEAL Study Result Conference Call. There will be a question- and- answer session to follow. Please be advised that this call is being recorded at the company's request. I would now like to turn the conference over to Mr. Ian Karp , Karyopharm's Senior Vice President, Investor and Public Relations. Please go ahead.
Thanks so much, Chad, and thank you all for joining us on today's conference call to discuss the results from the phase III SEAL study presented this morning at the Connective Tissue Oncology Society 2020 annual meeting. This is Ian Karp, and I'm joined today by Dr. Michael Kauffman, Chief Executive Officer, Dr. Jatin Shah, Chief Medical Officer, and Dr. Sant Chawla, Director of the Sarcoma Oncology Center in Santa Monica, California. On the call today, Dr. Kauffman will provide some opening remarks about the phase III SEAL study and results, and then Dr. Chawla will review the key findings from the study, which were presented for the first time this morning at the CTOS 2020 virtual annual meeting.
We will then open up the call for Q&A, for which we will also be joined by Dr. Mrinal Gounder, Sarcoma Service and Developmental Therapeutics Service at Memorial Sloan Kettering Cancer Center, who is also lead investigator in the SEAL study. Please note that Dr. Chawla and Dr. Gounder are not employees of Karyopharm and have been invited to participate on today's call as they were both investigators in the study and experts in the field of sarcoma. Their comments and opinions shared today are completely their own and do not reflect official statements from Karyopharm or their institutions. Earlier today, we issued a press release detailing the results from the phase III study. This release, as well as an accompanying slide presentation, are available on our website at karyopharm.com.
Before we begin our formal comments, and for those following along on the slide presentation, you'll see on slide three, I'll remind you that various remarks we'll make today constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. These include statements about future expectations, clinical developments, regulatory matters, timelines, potential success of products or product candidates, including our expectations relating to the commercialization of XPOVIO. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent quarterly report, which is on file with the SEC, and in other filings that we may make with the SEC in the future. Any forward-looking statements represent our views of today.
While we may elect to update these statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. With that, I'll now turn the call over to Dr. Michael Kauffman, Chief Executive Officer.
Thank you, Ian, and good afternoon, everyone. We are delighted today to discuss the positive pivotal results from the phase III SEAL study, which met its primary endpoint with a significant increase in progression-free survival in patients with unresectable dedifferentiated liposarcoma. This is Karyopharm Therapeutics' first positive pivotal study in a solid tumor indication, and we believe represents a major advance to the development and commercial potential of XPOVIO in oncology. We are tremendously excited about the results presented virtually this morning in an oral presentation at the CTOS annual meeting and believe they are particularly encouraging because advanced dedifferentiated liposarcoma remains a very difficult to treat cancer with no established standard of care and limited treatment options available to patients with heavily pretreated disease. Importantly, XPOVIO is the first oral therapy to show activity in a randomized trial in patients with previously treated liposarcoma.
Before we discuss the SEAL study in more detail, I'd like to take a moment to briefly provide some perspective on the foundational and unique approach we are taking toward innovating cancer drug therapy. On slide four, we have highlighted five core pillars of cancer drug therapy, which are all foundational and used across tumor and patient types, often in combination, to give each patient the best chance at clinical improvement. XPOVIO is the first approved anti-cancer drug whose primary activity is the activation broadly of tumor suppressor proteins. There are about 20 of these proteins, including p53, BRCA1 and BRCA2, retinoblastoma protein, and the inhibitor of NF-κB, called IκB, which are a critical part of each cell's own natural defense mechanism to prevent the generation of cancer cells and to direct a cell which has become cancerous to commit suicide.
This broad anti-cancer mechanism is potentially relevant to any malignancy. Our goal is to continue to demonstrate the impact that XPOVIO can have in combination with drugs from all of the other pillars in order to maximize the impact that XPOVIO can have on improving outcomes for a large variety of patients. Turning now to slide five. Our clinical strategy for XPOVIO continues to be to innovate with a purpose. Specifically, our approach has been to demonstrate meaningful activity in difficult-to-treat patient populations, and then to expand dramatically into earlier lines of treatment and additional tumor types, particularly in combination with other anti-cancer drugs. This strategy has been evident in our approach in both multiple myeloma and DLBCL, where we began our successful STORM and SADAL studies, and has led to subsequent development in earlier-line in combination settings.
Similarly, now that we have seen the positive phase III SEAL data, we plan to follow the same path and continue and expand our clinical development approach in a number of important and much larger solid tumor indications, including endometrial cancer with the ongoing phase III SIENDO study, lung cancer, glioblastoma multiforme, and melanoma, which have been selected based on encouraging clinical data and commercial potential. If you'll please now turn to slide six. Here we have an overview of soft tissue sarcomas, which are a diverse group of rare malignant tumors that originate from the mesenchymal cells within the soft tissues, including fat, muscle, nerves, and others. As outlined in the left pie chart, liposarcoma, which occurs in the body's fat cells, is the most common subtype and accounts for approximately 20% of all sarcomas.
According to the National Cancer Institute, in 2020, about 13,000 new cases of soft tissue sarcoma will be diagnosed in the U.S., and over 5,000 Americans will die from this disease. Common first-line treatments for sarcomas include radiation, surgery, and chemotherapy. Advancing now to slide seven, we'll have a deeper dive into the current treatment paradigm for dedifferentiated liposarcoma, which is a high-grade type of liposarcoma that grows more aggressively than a low-grade, well-differentiated liposarcoma. Dedifferentiated high-grade liposarcoma is associated with a poorer prognosis. The median overall survival of these patients is unfortunately just 2.5 years. For patients whose disease is not fully resectable with surgery, first-line treatment is typically chemotherapy regimens including doxorubicin alone or in combination with ifosfamide. Response rates are typically low, and essentially all patients will need additional treatment options.
In patients whose disease progresses following frontline therapy, typical treatments include trabectedin, where previous studies have shown a 2.2-month median PFS, and eribulin, which has been shown to have a 2.0-month median PFS in patients with DDLS. On slide eight, we highlight that most sarcoma patients in the U.S. are treated at centers of excellence that have particular expertise in treating patients with these types of tumors. There are about 90 Sarcoma Alliance affiliated centers in the U.S., and the SEAL study included patients at 26 of these sites throughout the country. In fact, the SEAL study was the largest trial ever conducted in patients with dedifferentiated liposarcoma. Should XPOVIO ultimately receive FDA marketing approval in DDLS, we believe we could effectively commercialize in this setting with a very small sales marketing effort, primarily leveraging our existing infrastructure.
I'd now like to ask you to move to slide nine, where Dr. Chawla will detail the results from the SEAL study. Dr. Chawla?
Good day, everybody. I hope this COVID crisis soon over and we have a good, better political climate, but we are very excited to hear the presentation for our patients who suffer from sarcomas. Dedifferentiated liposarcoma. Sarcoma or all cancers are like criminals in the body, and the low-grade tumors, which is like a well-differentiated liposarcoma, is like a low-grade criminal, like pickpocketing, home robbery, and other things. While dedifferentiated part is like a gangster. Not only it damages the organ where it is, but it metastasizes, it goes all over the body. This drug is the first drug. We did a very rigorous randomized study in multicenter, largest number of patients, and a unique drug which is not chemotherapy, which we have only used.
Just to declare that I'm not employee of the company as stated before, I don't have any conflict, and I will devote the 25 years of my life in taking care of the sarcoma patient. I'm participant to this study as well as I have played a pivotal role in approval and study of the previous drugs approved in liposarcoma, such as trabectedin and eribulin. I'm on slide 10. selinexor, as stated by Dr. Kauffman, demonstrated anti-tumor activity in the cell lines preclinical studies, and in phase I study, it showed impressive response of 40%, as shown in the graph on your right side with the multiple patients. I'm moving to slide 11. This was the largest study in 285, which is almost 300, two-one randomization. That means almost 200 patients received the actual drug, and 97, which is almost 100 patient, received the placebo.
Patient had to show that the tumor was increasing by the radiological means, which was confirmed by the blinded radiologists. That means they didn't know they were not blinded. They were obviously blinded from the results. The scans were performed on progression and confirmed progression. The label was opened, and if the patients were on placebo, were crossed over to actual drug. The drug was oral, given 60 mg twice a week. I'm moving to next slide, which is slide 12. Inclusion criteria were standard that confirmed diagnosis, progressive disease within six months, and patient must have received at least two prior treatment. The standard treatment are doxorubicin and other chemotherapy, but maximum over five, and standard lab criteria to be enrolled in the study.
A patient were allowed even some mild renal insufficiency and creatinine clearance up to 30 ml per minute because this drug does not cause any nephrotoxicity. Slide 13 shows the characteristics of both patients who are in selinexor group and placebo group. As you see, they are reasonably well-matched for age, sex, race, geographical area, performance status, and site of disease. Majority, as you see, 80% were in retroperitoneum or in abdomen. As you see, in both groups are about 70% had metastatic disease. Next slide, which is slide 14. Again, continuing the characteristics of the patients which are both matched both in selinexor group as well as in placebo group. Coming to the slide 15, shows the randomization, the 285 patients, 187 to the actual drug.
The drug was well-tolerated in majority of the patients but was discontinued in 57% because of disease progression, while in 69%, which is about 12% more because of the disease progression in the placebo group. Rest of the things are similar as shown here. Currently, 18 patients are continuing on the active drug on the selinexor. Next. This is the Kaplan-Meier curve, which shows the slight separation of the curve and showing there was a significant PFS in selinexor 2.83, which we expected at 2.7 prior to the study start, and it met the criteria, while the placebo PFS was 2.07 with a two-sided P value of 0.02. Hazard ratio of 0.7, that means 30% risk reduction in the relapse. This is significant, met the criteria, and it is similar PFS in the previously approved drug like trabectedin and eribulin.
Next on slide 17, it shows the overall survival, which is similar. These cross at multiple places, although numerically selinexor survival was 10 months and placebo was 12 months. As we have said, those patients who were on placebo did get selinexor, so it is not appropriate comparison. This is also not statistically significant. We are on slide 18, which shows overall survival again in the patients who initially only received selinexor, whether to start with or on the placebo. As you see, selinexor group had a survival of about 10 months versus placebo, which is nine months. Again, it is not statistically significant. Overall response is shown on slide 19. As you see, the RECIST criteria showed there are 2.7% of the patients in selinexor achieved partial remission, which is a definition of more than 30% reduction in the tumor.
If you took the overall group, which is more than 15% reduction in the tumor was in 7.5%, while those 97 patient in placebo, there was no patient showed either more than 15% reduction or no patient showed more than 30% reduction. There was no RECIST criteria response in placebo group. This slide of 20 shows the overall response who did not crossover during open label. Finally, the 5.3% patients who achieved the response Let me say again. More than 15% reduction was seen about 5.3% of the patient who received selinexor after crossing over, and 3.5%, which is similar, showed partial remission, more than 30% reduction in the tumor size. Overall side effects were well-tolerated, substantially less than any of the chemotherapy. There were no drug-related deaths.
If you see the Grade 3 and 4 in the right-hand column were in less than 10% and predominantly contained nausea and vomiting. Other mild side effects noted included fatigue and dysgeusia, which is a change in the taste. Next slide. Serious side effects like anemia, thrombocytopenia was rare, and anemia was in 18% in selinexor group and 8.2% in the placebo group, and it's mostly related to the disease rather than the drug. Of course, mild anemia and thrombocytopenia or neutropenia can occur with the drug in less than 10%-20%. Next slide. In conclusion, this is the first novel drug, which is an XPO1 inhibitor targeted drug, which has shown effective in dedifferentiated liposarcoma. We do not have any other drug specifically approved for this disease, although for liposarcoma we use doxorubicin, trabectedin, and eribulin.
Overall activity of this drug was similar to them, and it is an oral drug. Future of the drug, this drug can be combined with other drugs and as stated earlier, this drug has a unique mechanism of action, can be combined with chemotherapy, immunotherapy, and is already approved in myeloma and non-Hodgkin's lymphoma. If you have any questions, I'll be happy to answer. Thank you for your participation in this call.
Thank you, Dr. Chawla. With the positive SEAL data now in hand, we look forward to submitting a New Drug Application to the U.S. Food and Drug Administration during the Q1 of 2021, requesting approval of XPOVIO to treat the patient population studied in SEAL. If approved, XPOVIO would represent the first oral non-chemotherapy agent available for patients with dedifferentiated liposarcoma. Beyond liposarcoma, as we think about other solid tumor indications on slide 25, we show areas that we plan to explore. As I mentioned earlier, we are already collecting data from our non-small cell lung cancer, glioblastoma multiforme, and colorectal cancer studies and have begun to explore additional settings where we'd like to initiate new studies.
We plan to explore XPOVIO either alone or in combinations in a wide variety of lines of therapy and clinical settings in the future, including in ovarian, endometrial, GBM, non-small cell lung cancer, colorectal cancer, and melanoma. Ultimately, we view XPOVIO as a novel tumor suppressor activator and a potential pan-cancer drug that could become an important option for patients across both blood cancers and solid tumors. We see XPOVIO's greatest utility as a combination partner with other anticancer drugs and dosed only once per week in these combination settings. With that, I'll now turn the call back over to the operator for questions. Operator?
Thank you so much. We will now begin the question- and- answer session. To ask a question, you may press star then one on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. We please ask that you limit yourself to one question and one follow-up. If you have additional questions, you may reenter the question queue. At this time, we will pause momentarily to assemble our roster. The first question will come from Brian Abrahams with RBC. Please go ahead.
Hi, this is David Sisu on for Brian. Congrats again on the data and initial success in solid tumor. I guess just to start, you mentioned development in several solid tumors planned imminently perhaps next year. I guess I'm just looking for more color here, and maybe could you provide some color on where and how you might prioritize across these solid tumors as you think about factors such as mitigating trial performance in this current environment with increasing COVID lockdowns or any regulatory considerations as you engage the FDA with liposarcoma data? Thanks.
I think for the COVID lockdowns, hopefully the vaccine will get out relatively quickly, and we'll be able to relieve some of the stress going on. The fact is that these tumor cells keep dividing even in a pandemic, and these patients are in dire need of additional therapy in pretty much all of the solid tumor lines of the areas that we spoke about. The current ongoing studies are well supported by phase I data from the company and/or Investigator-Sponsored Trials that have been going on and where we're privy to some of the early data from those studies.
That's what led to the initial trials that we're carrying out right now in non-small cell lung cancer in combination with docetaxel, the combination with pembrolizumab in CRC, and the ongoing studies that we have in glioblastoma multiforme may now move from second and third line into first and second line. For additional tumors, we have demonstrated in phase II studies single-agent activity in ovarian cancer, and we've also demonstrated single-agent activity in melanoma, and this melanoma activity was further strengthened by the investigator-sponsored trial results presented this year at ESMO from MD Anderson, showing what appears to be at least additive activity of selinexor plus KEYTRUDA in frontline melanoma.
Basically, we're looking at the clinical data that are available to us and additional data that are not public, and we will be making decisions on going forward for the company-sponsored trials, including on the size of these markets and the overall unmet medical need. I don't know of any particular regulatory specific hurdles that are in place at this time as essentially all of these tumors remain incurable. Next question?
Got it. Thank you.
The next question will come from Maury Raycroft with Jefferies. Please go ahead.
Hi, everyone. Congrats on the updated data. Thanks for taking my question. First one is just on dosing strategy. In hemonc, I think part of the strategy there is to get patients to respond and then you can optimize dosing for the patient and manage tolerability. Do you think the dosing used in SEAL is in line with what will be used in the real world in liposarcoma or is there some optionality possible in the real-world setting? For Dr. Chawla, I was wondering if he can talk more about combo dosing strategy that doctors might use in the real-world setting and what data from SEAL can potentially help guide how to combine other drugs.
Okay, sure.
We'll start with Dr. Chawla because he may have things on-
Yeah. If Dr. Chawla, are you still able to be on? I'm not sure.
Yes.
If not, Dr. go ahead.
This drug is an oral drug, long half-life, given twice a week, this is very easy to combine with all other drugs. Since the side effects are minimal of this drug, systemic toxicity of myelosuppression or immune toxicity is minimal. I think it'll be a very well combination effort and can be easily combined, the real question will be the efficacy, if this drug could be more efficacious and more synergistic, our hope it will be because this is a unique mechanism of action.
Briefly, Dr. Shah, and Jatin Shah, maybe you can speak to the MD Anderson study. I think we're doing combination work with eribulin there.
Yeah, exactly. We're developing combination data and we're studying preclinically. There's data in combination with various agents. In the clinical setting, there's ongoing kind of investigator-sponsored studies both looking at Selinexor within that, GIST, so sarcoma subtype, as well as with eribulin for ongoing ISTs. We're exploring other options as well.
Got it. Thank you for taking my questions.
Thank you.
The next question will come from Peter Lawson with Barclays. Please go ahead.
Great. Thanks for taking my questions. Just maybe for Michael initially, just your thoughts on the PFS that kind of dropped from phase II- phase III. Is that anything we should be concerned about? Is that just kind of a larger end number? Is there anything else we should be thinking through?
I think our assessment, a couple of points are very important. The first one is that the PFS of trabectedin was reported at 2.2 months in an earlier population. The PFS of eribulin in an earlier population was reported at 2.0 months. Here now with the first non-chemotherapy oral therapy, we're talking about a 2.8 month PFS, which doesn't sound like a lot perhaps. When you have this devastating disease and you're in third line with no options, this is pretty interesting that you could have a PFS that's in the range or higher than what's been reported in earlier therapy. I'll turn it over to Dr. Gounder in just one minute. I think the move from phase II to III is just the numbers of patients and the more robust data set that we have now.
Dr. Gounder, do you want to add anything?
Yeah, absolutely. I'd like to echo a lot of the comments you just made. If you just look at, this is really heavily pretreated patients who mostly they've all had doxorubicin, they've had eribulin or trabectedin, now coming in in the third line to the fifth line setting. When we look at the retrospective data from many, many institutions, Sloan Kettering, MD Anderson, Europe, for just the dedifferentiated liposarcoma patients in the first line setting with doxorubicin, the PFS is 1.5-two- 2.5 months. These are all in that ballpark. Even with combinations like, say, doxorubicin plus ifosfamide, the PFS gets a little better, but the vast majority of the median PFS in the first line setting with doxorubicin-based agent is somewhere between two-four months at most.
In context of that, it's really surprising and very promising that in the third line setting in patients who failed all these drugs, Selinexor is performing just as well as doxorubicin, which frankly came to me as a big surprise. It was very encouraging, to say the least.
Thank you.
I would like to add the comment to Dr. Gounder's comment. When we talk about the improvement in the PFS about a month or a little less, it doesn't mean that everybody gets that much benefit only. There is obviously big range. We have to decide some parameters as a PFS for improvement. If this was in the financial world where everybody gets, some people get rich, some people lose money, and that cannot be decided. I treat the patients. There are patients who can get long-term benefit for months, and some patients, even on trabectedin, eribulin, and even this drug, go for a year or two years. Of course, those are the minority of the patients. We just can't define at this stage, but that's what we are looking.
The average improvement for about four weeks does not mean everybody only gets improvement in four weeks. Thank you.
Thank you.
Yeah, if I could just reiterate that. I think the other point, another way to look at it is that the tail of these curves is that we're approximately doubling the people with the long-term benefits, which is quite important to those folks. It's reminiscent, frankly, of other novel therapies where the medians are perhaps less affected than an important minority of patients who have a real benefit that otherwise would be left without therapy.
Great. Thank you. Then a follow-up for the doctors on the line, just whether you could potentially use this, I guess, either in earlier line or outside the dedifferentiated liposarcoma, just your thoughts there based on the strength of the data you've seen.
Yeah, no, if I could jump on that question. Yes, the study was designed in the third line and beyond setting. When you look at the totality of the PFS benefit, it's in line similar to drugs in the second line and even the first-line setting. Personally, if I were to see a patient, there are many patients. You can see here that many of these patients were 65 years of age. The median entry is 65, and 10% of patients were 75 years of age. These are patients who have other comorbidities that could preclude drugs like doxorubicin. We can only give six cycles of doxorubicin, then we have to stop for cardiotoxicity and then switch to something else.
I think on a case-by-case basis, one can make the argument to use this in an off-label setting for an individual patient and, of course, have that conversation with the patient. I personally think patients would prefer a drug like this, given that it had no neutropenic fever, had an oral dosing convenience compared to a classic cytotoxic chemotherapy. Patients are always asking, "Are there oral pills for convenience, or are there drugs that are targeted?" Here, we don't know the exact precise target, but I think a lot of that work will hopefully, future work will show that even within the study itself. In summary, I do think that We don't have to wait till the third, fourth, fifth line before we think about this drug.
I don't think I will be thinking about it in the event that this gets approved by the FDA.
Perfect. Thank you so much.
The next question will be from Jonathan Chang with SVB. Please go ahead.
Hi, guys. Congrats on the data, and thanks for taking my questions. First question for Dr. Chawla and Dr. Gounder. Can you help us contextualize the survival trend that was in stat sig in this GIST-like disease setting?
Yeah, I can take that. If you look at the overall survival, I think there is numerical differences, but the hazard ratio is solidly one. A lot of it is probably related to the crossover of about 60% of patients crossing over. There is a survival trend, but I'm not sure how much we can, and we definitely see this hazard ratio, but I'm not sure how perfectly those arms are balanced or if they are randomized. I think it is what it is. I'm not sure we can say a whole lot about it. I don't know if Dr. Chawla or Michael or someone else wants to add more to that particular one.
Well, I can just give some context on the regulatory discussions. The point of the overall survival endpoint, given the crossover, because we all know that crossovers, especially given that these are rapid crossovers, typically less than two months on the placebo arm crossed over, is that you muddy the waters downstream because you end up with a selinexor versus selinexor study. The point of the regulatory endpoint was to make sure there was no inferiority here. The fact that we came in with a hazard ratio of one or just slightly below one is great news.
As Dr. Gounder said, when you actually look at the patients who did not cross over to selinexor, and you can do all sorts of sensitivity analyses, which have been done but obviously couldn't be included in the short talk today, you end up with this at least trend that suggests that getting selinexor at any time is better than not ever getting selinexor. The P value is about 0.12 or 0.14, and we'll have to wait over time as more events accrue. At least it's trended in the right direction to suggest that getting some selinexor is beneficial. Dr. Chawla, did you want to comment?
No, I echo both comments of Dr. Gounder and Dr. Kauffman.
Great. Thank you.
Got it.
Three doctors that agree. That's pretty scary.
Second question from me. Can you talk about how the adverse event profile in SEAL compares with the experiences in liquid tumors?
Yeah. Maybe I'll ask Dr. Shah on our side to take that. Jatin?
Yeah, absolutely. Great question. I think the first key point is that the side effects that we see with selinexor are all very clearly dose and schedule dependent, as well as disease dependent. What we see with compared to initial STORM in myeloma, we have much lower doses with this, and so obviously it's going to be better tolerated. If we keep in mind that some of what we saw with STORM, for example, was in seven prior therapy with multiple myelosuppressive regimens. Very different patient population and dose, which in that setting, as we're starting to use these with lower doses in earlier lines of therapy, it is better tolerated. We see an improved side effect profile qualitatively where we see lower Grade 1, lower incidences and lower intensity of side effects.
Importantly, even when we compare to the same dose of 60 mg from the SEAL experience with similar dosing schedules, we see a better side effect profile in these patients with sarcomas. They've had less myelosuppressive therapy, less bone marrow involvement from heme malignancies. As we move into the solid tumor space, we see a better side effect profile with less myelosuppression.
Yeah.
As the future goes, obviously we'll continue to move more to weekly in combination, and so that will continue to kind of change the side effect profile that we see.
Got it. Thank you.
Next question.
The next question is from David Lebowitz with Morgan Stanley. Please go ahead.
Thank you very much for taking my question. When you look at these results, I guess, how does it translate to the broader soft tissue sarcoma population? Does liposarcoma results typically translate to these other indications, and do physicians typically use them off-label in these other indications?
Maybe Dr. Gounder and then Dr. Chawla.
Yeah. No, I can take that question. I think the short answer is yes. I think there is a value for selinexor in soft tissue sarcoma, and we haven't yet found exactly who those patients are. We did have a very nice hint of activity in a phase I study that was published in the JCO maybe about three, four years ago, where we saw it was a all-comer sarcoma study, and we clearly saw activity in D-diff liposarcoma. We also saw activity in leiomyosarcoma, MPNST, and a couple of other things. If you open up that paper and look at it, you'll see pretty impressive swimmers plot. The reason I think at that point we didn't really sort of go broad is we really want to have a focused question and sort of a focused regulatory pathway.
Some of the other sarcoma, such as leiomyosarcomas, have had specifically other drugs approved. We felt that from a straightforward regulatory pathway and to keep the study really clean, we'll focus on d-diff liposarcoma. What was also interesting is in that study, we saw some signal in something called MPNST or malignant peripheral nerve sheath tumor. This is not yet published, it's currently under review. Surprisingly, I've seen in my own clinic several patients responding to selinexor, which we are using as a single patient use. I think as this drug becomes more and more gets into our hands, there will definitely be people evaluating in different sarcomas. A lot of that is going to be dependent on sort of data, even if it is a small case series and things like that.
Thank you for taking my question.
The next question is from Arlinda Lee with Canaccord. Please go ahead.
Hi, guys. Congratulations on the data. I had a couple of questions for Dr. Gounder and Chawla. You guys have both worked on other drugs and other registrational trials. I was curious, one, what proportion of sarcoma patients are dedifferentiated? If a patient comes in, what kind of drives your decision on what therapy to give them, and how might this fit into the treatment paradigm?
Dr. Chawla, you want to go first?
Yeah. Overall, we have very limited therapy. Patients when they come with sarcomas, first thing is surgery if they are localized. If they are metastatic disease, standard chemotherapy and then other chemotherapies. Standard chemotherapy is doxorubicin and liposomal, which are substantially more toxic. Most patients will not respond. We move to the second line, which are like trabectedin, eribulin or clinical trials. There is a big unmet need in these diseases. As far as the liposarcoma makes about 20% of all sarcoma
Dedifferentiated liposarcoma makes another 20% of those. It's a rare disease, but unmet need for any effective or promising drug. That's why we are excited about selinexor.
Yeah, I can just piggyback off that comment. I think everybody in our field has a knee-jerk reflex to use doxorubicin, and we've been using it now for four decades. We've never really dived into the specifics of how good is doxorubicin in combination drugs, specifically for de-diff lipo. It doesn't look great. I think our field as a whole, this knee-jerk reflex to use doxorubicin single agent or in combination in the upfront setting, we will need to think more carefully. To answer your question, I don't think any of these single drugs improve overall survival. I think a lot of this is one should really have a personalized approach to an individual patient and not just have this algorithmic knee-jerk reflex of doxorubicin, and then this and then that.
I think our field, we are aware of it, but there is a certain sort of this conditioned response to doxorubicin and other drugs. I think that will change in the very near future.
Thank you. Could I ask a follow-up? Since somebody mentioned off-label use, since selinexor is already approved in myeloma, have you tried to use this off-label for other patients before? Thanks.
As I mentioned, we've tried to use it off label for MPNST. It really came as a single patient use program that Karyopharm has. To be honest with you, people who work in the solid tumor world, there's a huge barrier to start using drugs in the heme world. First, most people kind of don't really crisscross between the two, many people may not even be aware if you're just taking care of solid tumor patients about drugs in myeloma or lymphoma. That's especially true in the bigger institutions. I think if and when there is an indication in a solid tumor and there is safety in solid tumors, the threshold to try it in an off-label use really goes down a whole lot.
A lot of these use of off-label drugs is really also dependent on how an individual's insurance company also reacts to a request like that. Even if a patient or physician is willing, the insurance companies may not always agree to that off-label use.
I would like to comment about this off-label use. Although these are rare tumors and only certain big companies or companies like this one has ventured to do a trial for rare diseases. It takes a long time, and we try to use the off-label drugs, but we face a big challenge. These drugs are expensive. Most of the time, insurance company will deny. They will write to have two review papers, and those papers cannot be done without any clinical trials. Sometimes the drug companies are very kind enough and will give us the drug off label. Unlike 15- 20 years ago, where we could use any drug as long as it was approved in the market, off-label use is very difficult now.
Okay. Thank you very much.
Thank you all.
Ladies and gentlemen, this concludes our question- and- answer session. I would like to turn the conference back over to CEO, Michael Kauffman, for any closing remarks.
Thank you very much. I'd just like to thank everybody for joining our call today, and we look forward to chatting with you in the near future. Have a great day.
Thank you, sir. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.