Good morning, everyone, and welcome to the Leap Therapeutics DKN-01 Clinical Perspectives Conference Call. Following the presentation, there will be an opportunity for questions. Please be advised that this call is being recorded at the company's request. At this time, I will now turn the call over to Mary Jenkins of Argot Partners. Please go ahead.
Thank you, Chanel. Welcome and thank you for joining us today for Leap Therapeutics' DKN-01 Clinical Perspectives Conference Call and Webcast. I'm Mary Jenkins with Argot Partners. With me today are Douglas Onsi, Leap's Chief Financial Officer, and Dr. Samuel Klempner, Director of Precision Medicine and GI Oncology Program at The Angeles Clinic. This call is being accompanied by a slide deck, I'll ask that you please turn to our forward-looking statements on slide two. Before we begin, I would like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the Risk Factors section in the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC. Any forward-looking statements represent our views as of today, October 22nd, 2018 only. A replay of this call will be available on the company's website, www.leaptx.com, following this call. With that, please turn to slide three, I'm pleased to turn the call over to Doug Onsi, Chief Financial Officer of Leap.
Good day, everyone, and greetings from Munich. I'm very happy to be here with Dr. Samuel Klempner and to have the opportunity to discuss the combination study of Leap's DKN-01 and Merck's KEYTRUDA at that midway point in the study. Dr. Klempner will start off by describing the challenges of treating esophageal gastric cancer patients and the unmet medical need. He will review the clinical data presented in our poster yesterday, which was very well received by the attendees and will go into further detail with respect to a number of the patients. For those of us who work on the program day-to-day, the outcomes of individual patients have enormous impact. Last, we'll take questions from the analyst community. We're enthusiastic about the data that's emerging, we hope we can communicate that enthusiasm on the call. Now I hand it off to Dr. Klempner.
Thank you, Doug. Thank you all for coming. I'm going to try to put this data in perspective of the larger esophageal gastric problem in the U.S. and also globally. On this slide, we're just highlighting the scope of the problem. This is a disease that although somewhat less common in the U.S., as you can see, globally represents the third leading cause of cancer-related death with between esophageal and gastric, nearly 2 million cases in a year. Unfortunately, we haven't made significant progress even though we've known this is a significant problem for a long time. Within the U.S., which somewhat differs from the Asian countries, most of our patients are actually not diagnosed until they have very advanced disease. The chance for cure is very rare, and we have limited treatment options.
As you can see, that's clearly highlighted by the 5-year survival in advanced patients of less than 5%. Standard of care agents in the first line are active. As you can see, the durable benefit is infrequent and later lines of therapy have limited activity. These are patients that I think when you're looking at any clinical trial in the esophageal gastric space, you need to have an appreciation of the type of people that you're trying to help with these agents. The reason that this is a very difficult population is highlighted here.
These patients are highly symptomatic owing to the fact that the tumors are located in areas that affect the ability to swallow and therefore the nutritional status of the patients, which impact both their ability to tolerate standard of care therapies such as chemotherapy, but also significantly impact their ability to go on to clinical trials, often owing to performance status alone and symptoms from the disease. In fact, this is even more clear when you look at the fact that although the majority of patients who are diagnosed with metastatic disease do receive first-line therapy, the drop off from first-line to second-line is dramatic and arguably the highest among the most common tumors treated globally.
There's been a lot of SEER analyses and Medicare claims data suggesting that only about 40%-42% of patients who receive first-line therapy ever go on to receive second-line therapy. This is highlighting the problem of the symptom burden of these patients. Although there have been some molecular classifications which have added important understanding into the biology of the disease, we've yet to be able to translate some of these targets, largely receptor tyrosine kinases such as EGFR and MET and HER2 owing to the problem that this is a very heterogeneous disease. Targeting with a small molecule inhibitor, there's a lot of escape mechanisms within the tumor. This has been a limited strategy. There's clearly a need for novel agents and novel approaches in the second and later lines of therapy. Hence enter the trial, the LEAP study, which we'll be talking about.
This is just highlighting the paradigm of esophageal gastric cancers in the U.S. This has been outlined in the NCCN guidelines as well as several kind of white papers from various institutions. We break this down largely into gastric and gastroesophageal junction, particularly Siewert 2 and 3 and stomach. That would be on the right-hand side of the slide where it says gastric GEJ. True esophageal tumors, including squamous and mid-esophageal adenocarcinomas are less common and somewhat of actually a worse prognosis population. The standard of care is first-line systemic therapy. Generally, this is 5-FU and platinum, although there is a lot of variability within the U.S. In patients that are tested standard of care for HER2 and are positive, then Herceptin is added in both situations. Then you see the drop-off between the first and second-line therapy.
Response rates in the first line approach 50%-55%. What you see in the second line, save for the CYRAMZA and Taxol, which has a 28% response rate, this is the highest that we currently have available in the second line. There's a significant portion of patients who are not candidates for CYRAMZA owing to comorbidities. Then you see the 16% response rate to single-agent taxanes in this setting. In September 2017, pembrolizumab was approved for the treatment of beyond second-line gastric and gastroesophageal junction adenocarcinomas. It does not carry an approval for squamous cancers of the esophagus. Highlighting the KEYNOTE-059 data over here on the right, which shows the response rate that led to the approval. Only 11.6%. Actually, if you subtract the MSI-high patients from that, it drops into the single digits at around 9%.
Clearly, there's not a lot of durable responses and benefit in the second and third-line settings, a clear need for novel therapies. Here we see the schema for the LEAP trial. You can see there was a brief lead-in with a dose escalation of the DKN-01 drug from 150 mg starting to 300 mg, which was the intended dose. You may well know, there was data from the Taxol plus DKN-01 trial in esophageal gastric cancers clearly suggesting 300 mg was a safe and tolerable dose. Pembrolizumab was given a standard approved dose of six 200 mg dosing. Then after no safety signals were seen, this expanded to the larger study you see on the right-hand side, with the primary endpoint being safety and multiple secondary endpoints of response, biomarker analyses, and traditional clinical outcomes of PFS and OS.
This was a Simon stage design. If there were three partial responses, the study would expand to continue enrollment up to the full 60-patient study, which you see there. I think it's important to note that there was both PD-L1 naive patients, these are not exposed to KEYTRUDA, but also an important and very unmet need is trying to tackle the PD-L1 exposed and/or refractory population. This is the patient demographics of the currently enrolled patients. You can see here is that this is quite representative of the modern care of esophageal gastric cancer in the U.S. The majority of patients have received 5-FU and platinum therapy. Then you see the typical representation of second-line and later therapies and the types of prior therapy with taxane, ramucirumab, and immunotherapy, PD-1-directed therapy well represented.
You can see, I would call your attention to the PD-L1 expression, which is reported here. Again, this is centrally tested PD-L1 expression, and you see that the positive rates and negative rates are largely reflective of what we see in other study populations. Importantly, looking at the microsatellite status of these patients, you see that the majority, if not all, are microsatellite stable. There is a population that are unknown. This is an important point because in the KEYNOTE studies, the MSI-high patients are clearly driving some of the response. Tumor mutational burden, which is an emerging immunotherapy biomarker, is collected and among the known is reported here. Again, MSI-high tends to have very high tumor mutational burden. There's no other suggestion that those patients are captured here. This is the safety data, the treatment-related adverse events.
Really this is an encouraging safety profile when you look at combining immunotherapy agents. For example, for context, if you look at CheckMate 032, which is ipi/nivo in esophageal gastric cancers, there is significant rates of treatment-related adverse events, which is well described with the addition of ipilimumab to PD-1. Contrast that against here, where you see that the majority of treatment-related adverse events are very low grade and actually somewhat infrequent. In summary, I think there was no clear additive toxicity when you're adding DKN-01 to standard dose pembrolizumab. As an investigator, that's obviously an encouraging thing because these are patients where we're trying to balance both the quality of life and the quantity of life. A non-toxic therapy is very important. We're getting into the meat of the study.
This is the overall population with the objective response rate. Then we will talk about the evaluable populations lower down on this slide. You see among the evaluable patients, of which there are 23, so 62% of the accrued patients are evaluable, the response rate of 17.4%. Again, if you look back at the MSF GE junction in gastric patients in the KEYNOTE studies, this is just about a doubling of the response rate compared to when you throw out those MSI-high patients. Disease control rate, which I think is an important clinical outcome in esophageal gastric cancer of 56%. This is important because although it may not be direct tumor response, as you're seeing these patients, these are patients who are having their symptoms controlled, which often translates to improved outcomes. The median time to response of three months is consistent with what's seen.
In fact, it almost mirrors exactly what was seen in the CheckMate 142 study that was presented today at ESMO. No major changes there. Both early and late responses are seen with immunotherapy. This is a well-described phenomenon. This is an important table. You see, again, the promising overall response and disease control rate, especially noting that some of these are heavily pre-treated patients, which is an often difficult population to improve upon. There is, of note this is 23 patients overall evaluable, and I'm mainly focusing on the evaluable population on the right-hand side of the slide, where you see that over half of the patients have more than two lines of therapy and the response rate is pretty similar between second line and second line and beyond patients of 18 and 14.3%.
This is encouraging and also parallels somewhat what has been seen in other immunotherapy trials. To be honest, this is somewhat of an improvement in the later lines of therapy where there's been a drop-off in some other immunotherapy trials. Among the microsatellite stable known patients, there's a portion that are not yet known. We see an excellent response rate and disease control rate. PD-L1, which is a biomarker for immunotherapy of honestly debatable importance, but it's something that you need to capture because it is linked to the label of pembrolizumab. What you see here, this is the centrally tested PD-L1, in the positive population, where it's known the response rate is 33%. Equally important here, although the numbers are small, one of the four patients with a known PD-L1 negative population responded.
That's a very encouraging sign when you're an investigator because the response rate in PD-L1 negative patients from KEYNOTE-059 is about 6%. Obviously this will be exciting to follow as the number of evaluable patients increases as the data matures. These are encouraging numbers to have activity in a PD-L1 negative population that otherwise is generally not exposed to immunotherapy if KEYTRUDA is the only option. Here we see the waterfall plots and we'll see the spider plots as well from the evaluable population. What you see here is similar to what was shown in the table, and I think it will be important on the next slide when you see that some of these responses are quite durable. Here you see the partial responses and the stable disease, and this will be broken out by PD-L1 and microsatellite status on some subsequent slides.
Here is the spider plot with durability and depth of response. I'm sure you all have seen plots like this in the past. This is including all patients who are available, and this is on study and off study, and you can see that the lighter yellow is off study. Durable response is out to beyond 250 days. The reason that patient is a lighter yellow is that they are off study, but it was after the time of the data cut for that analysis. Here we see, again, a subgroup analysis. It's important when you look at this study, if you think back to the earlier table, it actually includes esophageal and esophageal squamous cell cancers, which are actually not part of the label of pembrolizumab and an even more difficult population to treat. They tend to have lower response rates to actual all therapies.
When you focus in on the GE junction and the gastric cancer patients, which is highlighted on this slide, that's a better comparator to the current approval for pembrolizumab. That's what we're trying to show here. Here you can see that stratified by one or more prior lines and by microsatellite status when it's known. Here in this perhaps more comparable population, you see the response rate of 23.5%. That 17.4 previously was dragged down a little bit by the squams and esophageal, true esophageal that are less responsive. This is probably a better comparator to put in context with the current approved landscape of GE junction and gastric cancer. Again, 23.5% is a little bit more than a doubling of the response rate when you look at single agent pembrolizumab given on label.
That's again shown down here on the KEYNOTE-061 and 059 data. 061 is a true second-line randomized phase III trial against paclitaxel in the second line, and KEYNOTE-059 is a single arm study of single agent pembrolizumab after second-line therapy. This is the slide that would get me excited as an investigator along with this next slide, which is again just showing the spider plot for that population, again the GE junction and gastric cancer patients. You can see both durable responses in people in the second line setting, one prior line and microsatellite stable. These are actually both my patients, so I can describe in a little bit more detail subsequently. You see the blue line as well, someone with more than two prior lines of therapy, microsatellite stable, also achieving a durable benefit.
Here again is just to try to put this in context and make it very clear for everyone on the call. You have to look at the populations of patients that were studied. Obviously, the size of the trial is important, and this is a study currently that we're talking about that will require some maturing of the data to see the full set. Across the top row, you see the response rates from the registrations trial. What clearly stands out is an over 10 doubling the response rate in this LEAP trial. Stable disease rate is intermittently reported in some of the studies, but again, here we're seeing an improvement, again, a doubling compared to the KEYNOTE-059, which is perhaps the closest comparator study to this. PFS is something that is important but remains to be fully matured from this data set.
Again, trying to break it down by the standard stratification factors, including PD-L1 and microsatellite status. There is no microsatellite high patients that are known on the LEAP trial. That 23.5% overall response rate is presumed to be all in MSS patients. It is. PD-L1 positive patients, the response rate is 33%, which again, is an improvement upon monotherapy. Response rate is actually quite important in these patients because the burden of disease is what causes the symptoms. Patients who respond, their symptoms improve, and they feel better, that, I think, will be highlighted in some of these vignettes that I'm about to show. I'm going to highlight a few patients. These happen to both be my patients, so I can certainly speak in detail if there's questions.
This is a patient of mine who was heavily pretreated and was presented on the prior call for those that were there. He had extensive metastatic disease, which is highlighted here, both in the liver and a perinephric mass. This is actually somewhat important because the rates of response with immunotherapy tend to actually be a little bit lower in the liver. When you see activity in visceral metastases like the liver, it's something that gets you a little bit more excited about a drug in general. Clearly a significant decrease here. This is an 82% decrease by RECIST. Patient remained on study over nine months with significant symptomatic improvement as well.
This is another patient that had previously shown some of the early data. This is a follow-up showing what is sometimes seen as a pseudo flare phenomenon, where if you actually look between the December 2017 and the January 2018 scans, the masses actually in the liver increased slightly, subsequently decreased and converted more to a cystic appearance. This is somewhat typical for some immunotherapy responses, and it's also mirrored by the serologic response in CA 19-9 decrease. Again, this is a microsatellite stable patient with a low tumor mutational burden, someone who may have been predicted to be less likely to benefit from PD-1 monotherapy. If you're potentially expanding the group of responders, that's an important component by adding a second drug. This is another microsatellite stable GE junction adenocarcinoma.
Again, you see a low tumor mutational burden, microsatellite stable status, and what's called a CPS 1%. One can be either accomplished by tumor cells or infiltrating immune cells. If you look at KEYNOTE-061, the responses are relatively low in this PD-L1 CPS-1 population. Previously treated with FOLFOX, you can see the baseline disease sites there highlighted on the three CT scans vertically and then going in time across in rows. You can see that what's highlighted by the best response over there is actually not the overall response per RECIST, but the decrease in each lesion going across. Lesion 1 going across in a row decreased by 12%, whereas lesion 3 decreased by 62%. Again, another GE junction adenocarcinoma, which is the most common subset in the U.S. This is a patient of mine who is ongoing on trial.
A younger man previously treated by first line as well as local regional disease with significant nodal burden of disease causing symptoms and pain, particularly that para-aortic node. You can see on his first scan a relatively rapid decrease in the size of that lymph node, which was associated with a normalization of his CEA and complete resolution of his pain. I do expect personally this patient to go on to become another responder, but that remains to be seen with follow-up scan. Again, another patient highlighted here that would be somewhat less likely to be predicted to respond. A PD-L1 positive patient with an intermediate mutation burden. This is an actual esophageal adenocarcinoma. These are patients who tend to be harder to get access to immunotherapy as well as tend to be less responsive. This was quite an encouraging single case.
Here another chemoradiation first-line therapy increasing lesions in the lung, esophagus, and nodes. By central read, this is actually a clear PR. By investigator-assessed response, it was also a near PR with a 28% decrease. I can certainly answer questions about the discrepancy there if asked. We presume this will go on to become a PR. When you look at any drug, you have to wonder about the mechanism of action and whether or not there can be any predictive biomarkers either for responders or people who will not benefit. This is very early data looking at the potential biomarkers for DKN-01 in combination with pembrolizumab. What you're seeing here is an RNAscope assay for DKK1, the hypothesis being that higher DKK1 expression may be associated with response.
Here you see the difference between a partial responder and someone who was primarily progressive, suggesting that lower DKK1 expression by RNAscope at baseline may be associated with a lower response rate. This remains to be validated in all of the samples that are collected and is certainly an area of ongoing interest. You can see on the right of the slide is that among the patients with DKK1 baseline status known, you can see that there does seem to be an enrichment for the responders and the stable disease patients in a higher baseline DKK1 expression. That's encouraging when the potential mechanism can be tied to the clinical outcome. Finally, another interesting aspect of immunotherapy in general is how to expand upon PD-1 therapy. There's a lot of interest in combining agents that manipulate the adaptive immune system.
That's PD-1 therapies that are primarily acting on T cells, CD8-positive T cells. Of course, there's another important arm of the immune system, which is the innate immune system. These are the primary defenders, you can think of them. Here you see some preclinical mouse models suggesting that DKK1 functions clearly superiorly in an NK-intact model. If you deplete the NK from a mouse and give DKK1, there's certainly significantly less activity than with an NK-competent model, suggesting that the mechanism may be mediated through NK cell activation, which is an area of intense interest in the immunotherapy field. Again, tying complementary mechanisms of action which may improve the proportion of patients who would benefit and may be bearing out in this study itself where you early signal a significantly improved response rates with the combination.
I will conclude the overview of the publicly available study data and just suggest that this is clearly a safe combination with very little additional side effects as we saw from the adverse event slide. The combination has a very promising overall response rate, and I can tell you from participating in this trial since the beginning that our patients have clearly benefited from this, including some of the stable disease patients, that the disease control rate is high on this trial, and that translates directly to patient benefit in my opinion. This is a heavily pretreated population, and you're seeing activity both in the much later lines as well as the second line. The mechanism and the response rates I think may tie together nicely, which is always a good thing when you're thinking about how to carry a drug forward.
Biomarker exploration is an area of intense interest but there seems to be a suggestion that DKK1 expression may be associated with the identification of responders where higher expression predicts for perhaps a better chance of response. The clinical study is ongoing. It's nearly fully enrolled. One thing that I'll remind you of is that the evaluable population that we presented is roughly half of the overall study. There's a significant portion of patients who remain on study who have yet to be scanned to see where their responses are to be included in an evaluable population. Consistent with other immunotherapy trials, particularly the HCC data and actually some of the CheckMate 142 that was presented today, there are patients who have been on therapy in some of those other trials for over a year before achieving a response.
If you look back to the spider plot which I showed, you see that the same thing has been shown here. It just highlights the importance for investigators, unless there's clear progression, to give that disease control rate a chance to convert over to a partial response and that can sometimes take quite a lot of time. I will give it back to the rest of the team and happy to take any questions.
Thank you. Ladies and gentlemen, if you have a question at this time, please press the star then the one key on your touchtone telephone. If your question has been answered, or you wish to remove yourself from the queue, please press the pound key. To prevent any background noise, we ask that you please place your line on mute once your question has been stated. Once again, ladies and gentlemen, that's star one to ask a question at this time. Our first question comes from the line of Rob Benjamin of Raymond James. Your line is now open.
Hey, good afternoon, guys. Thanks for taking the question. I guess just a couple for Dr. Klempner. Can you give some more color on the SDs that are seen in the trial? In your opinion, really how meaningful are they? I think there were a couple that you mentioned have the potential to turn into a PR, and I guess I'd want to know why. Then separately, out separate from the company, could you give us your own thoughts on how you'd like to see this combination developed going forward, and in what indications? For example, do you think we should stick with esophageal gastric or should we start exploring tumor-agnostic indications and target more MSI stable patients? Thanks.
Sure. I'll try. I can tackle the first one relatively straightforward. The second is a big question, but I'll try to give you some thoughts about it. The reason you asked about why might there be some patients who I believe will be converted to PR, I can certainly speak to my one patient who I presented the scans on, where he had a serologic biomarker, a protein called CEA, that normalized from quite elevated to normal after about the first two doses, first two cycles. By the time his first scan happened, his marker had already normalized. In my experience, when the marker goes from elevated into the normal range, that person is clearly responding, and sometimes it just takes a little bit longer than the first interval of the scan. This is sometimes done six, eight, nine weeks, depending on the trial.
Sometimes the scanning interval can play a part into when you see the response. I'm literally 100% convinced that my own patient is going to convert to a responder, which, of course, will be encouraging when you were to add that into the evaluable patients. Your response rate would obviously increase in that situation, which only adds my own excitement about getting more patients onto the combination. As to some of the other patients who remain on study in that stable disease kind of period, I think if they're tolerating the combination, which is clearly tolerable, then as of my clinical judgment would be to keep them on for as long as possible because of the pattern that's observed in this study and others where responses can sometimes not happen for a significantly delayed period of time.
Scientifically, I think that this trial offers a couple opportunities to maybe get at some of those questions, which when the science and the outcomes tie together, then that's when I think anyone gets very excited about a drug. One could hypothesize that perhaps the DKN-01 and maybe via an NK-mediated mechanism may actually be upregulating the PD-L1 expression, then the pembrolizumab, if that process takes a little bit of time, then the combination with pembrolizumab, one, makes a lot of sense, but two, it may explain why the responses can sometimes be seen a little bit later. I don't know if that answers the first part of your question.
Yeah, no, that works.
Your second question is about globally putting this in the context of esophageal gastric cancer, more importantly, where do you go from here? Globally, I tried to put this in the context of what is out there. The approved agent in the U.S. is pembrolizumab as a single agent for gastric and GE junctions who have failed more than two lines of therapy. Independently, there is a tumor-agnostic MSI-high indication. For the sake of this trial, there's no known MSI-high patients, and I suspect there won't be at all, so I don't think we need to talk about that part of the population. Although it is worth noting that that does kind of beef up the response rate and some of the durable responses seen in 059 are accounted for by those MSI-high patients.
You have to take that number probably a little bit inflated by the MSI patients in the KEYNOTE-059. 061, it's a little bit less. If your comparator is pembrolizumab, I think this is early data. It's demonstrating a significant improvement in response rate, which again, translates to benefit and allows people to stay on study, perhaps giving them the chance to convert to responders. How do you go forward from there? I think the most important thing is really to see the data mature a little bit and increase the number of evaluable patients and see those response rates and see if some of those other people convert. If it holds up with more mature data, I think you definitely have to explore it because that would be a very exciting improvement upon the current standard.
One could envision a randomized phase II trial in PD-L1 positive patients of pembro versus pembro plus DKN-01. I think that would be extremely convincing data. I think this trial will be an exciting trial for me and I think the gastroesophageal community. Yes, I think one out of four people who are confirmed centrally PD-L1 negative, that's the patient that one, they don't even have access to pembrolizumab on label because the label's only for PD-L1 positive patients. If your mechanism is expanding responses into the PD-L1 negative patients, I think something along the lines of pembro DKN-01 versus investigator choice would be a way to really confirm that activity in the PD-L1 negative population.
Certainly, if this is going to be driven by the data, I think in my own opinion, the company has gone about it in a smart way rather than jumping, which other companies have done, jumping from too early to phase III trials that have only been met with kind of mixed response. Going about it in a logical way trying to explore the activity, see something promising, understand the science and the mechanism, expand in a rational manner, I think is a much more likely to be a successful strategy rather than jumping into a study before you really understand your combination.
Thank you. Our next question comes from the line of Wang Zi Lei of Vattenfall. Your line is now open.
Hey, thanks for taking my question. The first one is the one esophageal patient you mentioned is considered a partial response by central review, but is stable disease by the local site. Can you elaborate more why there's such a big difference?
Yeah. This is kind of a nuanced aspect of RECIST. In RECIST version 1.1, if you call a lesion minimally visible, then your default measurement is supposed to be five millimeters. Whereas if you call the lesion completely gone, then it should be zero. When that patient, if you add up the lesions on RECIST, the difference between the zero and the five accounts for a difference of that PR versus stable disease. I think it's rare that a central review actually improves the outcome. Usually, central reviews, when you look at trials, tend to lower the response rates. In this case, I think the central reviews are independent, which is obviously a strength, and I think that in this case, that patient clearly has benefited and has had decrease. By central review is a response.
I don't know if that answers your question, but it's just that.
In the slide, you said that.
Yeah. It's a pulmonary lesion.
Okay.
The investigation-
The local site considered a 28% reduction, but the central review is 74% reduction for the same lesion? You mean the total sum of the lesion size? Using the same scan, right?
Yes. The central review and the investigators use the same scans. The investigator, which is not me in this case, deemed that pulmonary lesion, although significantly decreased, still technically visible. Therefore, it's defaulted to 5 millimeters. The central reviewer reads it as completely gone, so it's recorded as 0. RECIST uses the-
Got it
sum of the longest dimension. That accounts for the difference. If you have
Okay.
If you have a
Got it. Just to clarify for the other responses, it's all judged by the RECIST 1.1 criteria?
Correct.
Okay.
iRECIST, which is used in a lot of immunotherapy trials, is essentially identical to RECIST other than the use of a confirmation scan. Obviously, in the responders on the spider plot, they've been on long enough that they've had subsequent scans, which have confirmed the response to be real.
Got it. Thanks very much. Another question is about the I know that all the data is focused on the PD-1 naive cohort. We do have seven patients in the PD-1 refractory cohort. So far, no response rate. Can you have any further color on any benefits or patient performance in that cohort?
Yeah. I think, as you pointed out, the numbers are quite small. Again, stable disease in two of the six, so a third of the patients, I think that's encouraging. Who knows? Maybe there will be other PD-L1 negative patients that may convert to responders. This is a population that is extremely difficult to treat. These are patients who have seen essentially all the tools we have for stomach and esophagus cancers. To my knowledge, there hasn't really been any approach that has been able to reliably show activity in the PD-L1 refractory populations, really across tumors. Maybe some of these injectable approaches may add responses in those patients in melanoma, but we don't know if that holds true for tumors outside melanoma.
I think the stable disease rate is encouraging to me, that the lack of true responses is actually not that surprising because we haven't really solved that one. I would say that bigger numbers are needed. A stable disease rate of 33%, if it holds, would be enough for me to be excited and want to explore that population. I think you just need to see the data mature a little bit.
Got it. One more question about the esophageal subtype. Sorry. Currently, if this one patient turned to a partial response out of the six-
You do see about 15%, 16% response rate, right? On the other hand, if I remember correctly, the DKN-01 plus paclitaxel should have, I think, a 42% response rate in taxane naive esophageal cancer patients. I think it was esophageal-
plus GEJ, right?
That's correct.
I think the company is going to provide data update on that in this quarter. I just want to ask you, maybe it's too premature to judge the DKN-01 plus KEYTRUDA in the esophageal subtype Versus DKN-01 plus paclitaxel in esophageal subtype. So far, do you think it's plausible to maybe the DKN-01 plus KEYTRUDA, it's so far most data in the gastric and the GE junction subtype, and then the DKN-01 plus paclitaxel may be more active in the esophageal subtype?
I think that's a good observation and it's something that I can certainly speak to the Taxol plus DKN-01 because that data has been presented and is relatively mature. The response rate that you quoted is accurate. That's a significant improvement upon either the RAINBOW or single agent Taxol data. I think independent of this study, that data is interesting and exciting. It's hard to really draw a lot of conclusions in this pembro plus DKN-01 in the esophageal adeno or squamous from II and IV respectively. I think the fact that there is a responder in that population is in and of itself interesting and exciting because those are groups that are excluded from all of the KEYNOTE studies.
If you look at the inclusion for KEYNOTE-059 and 061, they actually restricted it to GE junction and gastric, partly because of that known phenomenon of lower response rates. To me, it's a signal, and it's interesting. It's really hard to say a lot more than that.
Okay, understand. Thank you very much.
Sure.
Thank you. As a reminder, ladies and gentlemen, if you have a question at this time, please press the star then the one key on your touch-tone telephone. I'm showing no further questions at this time. I would now like to turn the call over to Mr. Doug Onsi for closing remarks.
Great. Well, thank you all for your time on the call today and on the webcast. We appreciate your interest in LEAP and your interest in the DKN-01 program. We're very excited about where we are today and in this ongoing study. Really look forward to being able to present the more mature data from the full data set to you next year, likely in the second quarter. We very much appreciate Dr. Klempner's time today. The insight of treating a patient, I think, makes the data more real and easier for people to appreciate and understand. We appreciate the work of all of our clinicians and their staff and the patients who were part of this study. It's something that is terrific for the clinical population and what is a very underserved esophageal gastric cancer patient population.
We thank you all for your call time today, if there are any questions, please feel free to follow up with us at the company directly.
Ladies and gentlemen, thank you for participating in today's conference. This concludes today's programming. We all disconnect. Everyone have a great day.