Good day everyone, welcome to the Syndax call. Today's call is being recorded. At this time, I would like to turn the call over to Megan Myers of Argo Partners. Please go ahead.
Thank you, operator. Welcome, thank you to those of you joining us on the line and the webcast this afternoon for a review of Syndax's clinical development plans for the combination of entinostat and KEYTRUDA in non-small cell lung cancer. I'm Megan Myers with Argo Partners, with me this afternoon are Dr. Briggs Morrison, Chief Executive Officer, Michael Meyers, Chief Medical Officer, and Dr. Martin Edelman, Chair, Department of Hematology, Oncology, Fox Chase Cancer Center. Also joining us on the call today for the question answer session is Michael Metzger, President and Chief Operating Officer, Dr. Peter Ordentlich, Chief Scientific Officer, and Rick Shea, Chief Financial Officer. This call is being accompanied by a slide deck that is available on the webcast. I would like to first turn to our forward-looking statement 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 factor section in the company's most recent quarterly report on Form 10-Q, as well as any other reports filed with the SEC. Any forward-looking statements represent our views as of today, October 25th, 2018, only. A replay of this call will be available on the company's website, www.syndax.com, following this call. With that, please turn to slide three, I'm pleased to turn the call over to Dr. Briggs Morrison, Chief Executive Officer of Syndax.
Thanks very much, Megan, thank you to everyone for joining us on today's call at the short notice. We're excited about the agenda for today's call, which is shown on slide three. After I make a few introductory comments, Dr. Michael Meyers, our Chief Medical Officer, will walk through the data from the PD-1 refractory non-small cell lung cancer cohort of ENCORE 601 that we recently presented at the World Conference on Lung Cancer and will also walk through the study design of ENCORE 607, our proposed registration trial in non-small cell lung cancer.
Dr. Martin Edelman from Fox Chase Cancer Center was the scheduled discussant at the conference. We are very fortunate to have Dr. Edelman joining us today to provide his perspective on the emerging standard of care in non-small cell lung cancer, giving the presentation he was scheduled to give at the World Conference on Lung Cancer. We will take questions on the lung cancer data, the ENCORE 607 trial design, and Dr. Edelman's presentation, noting that Dr. Edelman is not available for the entire duration of the call. I will provide a brief commentary on the PFS results that we announced for the E2112 study and reopen the call to any further questions. Slide four provides a summary of the milestones we communicated on our last call in August of this year.
We indicated at that time that we would provide updates on E2112, our phase III breast cancer trial in patients with hormone receptor-positive, HER2-negative breast cancer, as well as non-small cell lung cancer and melanoma during the fourth quarter of this year. We have just announced that E2112 has completed enrollment of 605 patients, that the PFS result did not meet the high bar for statistical significance, and that the E2112 trial will continue as planned beyond the recently completed third interim analysis of OS with continued interim planned analyses conducted approximately every six months. I'll provide additional commentary on E2112 later in the call.
After returning from the World Conference on Lung Cancer and speaking with a number of lung cancer experts, as well as monitoring the data presented at ESMO quite recently, we are eager to share with you today the update on our plans for entinostat in non-small cell lung cancer. Slide five summarizes our ENCORE clinical trial program, in which we are testing entinostat in combination with PD-1 pathway antagonists. We've previously communicated that as we complete our initial clinical trials in each tumor type, we will prioritize which indications to advance to registration trials based upon unmet medical need, the competitive landscape, and our ability to generate an attractive return on our investment.
Taking those factors into account, we are pleased to announce today that we are moving forward with a registration trial in non-small cell lung cancer patients whose disease has progressed after both platinum-based combination chemotherapy and a PD-1 antagonist therapy, an area of clear unmet medical need. Before Dr. Meyers provides more details on this non-small cell lung cancer registration trial, let me call out two key points. The trial is designed to both validate the classical monocyte biomarker and to demonstrate that the combination therapy of entinostat plus KEYTRUDA is superior to standard of care chemotherapy in the high monocyte population of patients.
The trial will enroll approximately 200 patients with data potentially available within two years, the second half of 2020. This could position us to be the first novel therapy with regulatory approval both in the U.S. and the EU in the sizable population of lung cancer patients. This would also potentially be our second launch indication for entinostat following closely on the heels of breast cancer, thus enabling the build-out of a very significant franchise. Let me now turn things over to Dr. Michael Schmidt, our Chief Medical Officer, to review the ENCORE 601 data that was presented by Dr. Matt Hellmann at the World Conference on Lung Cancer last month. Michael?
Thank you, Briggs. Slide six provides a summary of the ENCORE 601 KEYNOTE-142 study design. Today, I will review the phase II data from patients with non-small cell lung cancer whose disease had progressed on a PD-1 pathway antagonist. These data were presented recently at the World Conference on Lung Cancer, as shown on slide seven. Slide eight shows the demographics of the 76 patients enrolled in this cohort. All patients had previously received both chemotherapy and a PD-1 antagonist. For about two-thirds of the patients, their last therapy before entering ENCORE 601 was a PD-1 antagonist, and the median time since last therapy was a little over two months. Most of the patients had not experienced an objective response to their prior PD-1 therapy.
Consistent with this clinical observation, the majority of patients had either less than 1% or 1%-49% expression of PD-L1 at the time of study entry onto ENCORE 601 using the validated Merck assay. Slide nine shows a waterfall plot for this cohort. The objective response rate for the entire study population was 10%, with a 95% confidence interval of 4%-19%. The median PFS in the overall population was 2.8 months. On slide 10, we show the spider plot for the full cohort, which highlights that the median duration of response was 5.3 months and that there were a large number of patients with prolonged stable disease in addition to the patients with objective responses. On slide 11, we show more detail on the responding patients.
You can see that most of the responders went on to our trial after progression on a PD-1 antagonist, and most were PD-L1 negative. On slide 11, we show the safety profile of the combination. In general, the regimen was tolerated well with a manageable adverse event profile. 14% of patients discontinued therapy due to a treatment-related adverse event. We have previously identified a biomarker that may predict clinical benefit. Slide 13 highlights a recent paper that identified classical monocytes, a sample from peripheral blood, as a strong predictor of both PFS and OS in patients with melanoma who were treated with a PD-1 antagonist. Based upon this paper and the well-described effect of entinostat on the monocyte lineage, we analyzed whether this same biomarker would predict clinical benefit in the 76 lung cancer patients we have just reviewed.
Slide 14 shows the swimmer's lane plot coded by baseline levels of circulating monocytes. The patients with the high monocytes are in green, and the patients with low monocytes are in the reddish color. As you can see, the majority of patients who experienced an objective response were monocyte-high patients. Notably, the monocyte-high patients also appeared to have experienced a significant increase in response to duration as well. Indeed, on slide 15, we show that both PFS and objective response rate are significantly improved in the population of patients with high peripheral blood classical monocytes. The PFS of about 5.3 months that we observed in the high monocyte population is roughly double the PFS that has been reported in the literature in patients treated with standard of care chemotherapy in this setting.
We have reviewed these data with physicians who are expert in the treatment of non-small cell lung cancer and in the development of novel agents for this disease. They uniformly found the data highly interesting and encouraged us to pursue further the development of entinostat in non-small cell lung cancer, especially in the high monocyte population. Slide 16 shows the treatment options most commonly used to treat patients with metastatic non-small cell lung cancer. As you are aware, it is common practice to use selection markers such as EGFR, ALK, PD-L1 expression, and tumor mutational burden to identify non-small cell lung cancer patients who are more likely to respond to various treatments.
We anticipate approximately 30% of patients whose disease has progressed on anti-PD-1 treatment would have high baseline peripheral monocytes according to our assay, and this would represent a large market opportunity for our combination of entinostat and pembrolizumab. Slide 17 shows the registration trial we designed for the entinostat pembrolizumab combination based on those discussions with non-small cell lung cancer experts, as well as input from the FDA. To be eligible for this study, patients must have received a platinum-based chemotherapy and pembrolizumab. We anticipate that most patients will have received the triplet of pembrolizumab, pemetrexed, and cisplatin, the regimen used in the KEYNOTE-189 study, and will have progressed while on maintenance pembrolizumab. Patients will also be included if they have received platinum-based chemotherapy as first-line treatment, followed by pembrolizumab. We will first assess the percent of baseline classical monocytes in peripheral blood using a validated assay.
Those patients with low monocytes will be treated with entinostat plus pembrolizumab. Those with high monocytes will be randomized to be treated with standard of care chemotherapy as per investigator's choice versus the entinostat pembrolizumab combination. The primary endpoint of this study is PFS based upon the impressive PFS data we saw in phase II. The statistical approach will be to first test arm A entinostat pembrolizumab in patients with high monocytes versus arm C entinostat pembrolizumab in patients with low monocytes to validate the monocyte biomarker. The second statistical analysis will be arm A entinostat plus pembrolizumab in patients with high monocytes versus arm B, standard of care chemotherapy in these same patients with high monocytes. The secondary endpoints will include objective response rate, duration of response, and overall survival, all of which are important in proving the efficacy and benefit of this regimen.
The trial will have limited power to assess an OS benefit. We recognize that. However, we do think that PFS serves as a basis for full approval in the United States and at least conditional approval in the EU. As you can see, the total number of patients is approximately 200. We anticipate completing the trial and having top-line data both validating the biomarker for patient selection and proving the efficacy of entinostat and pembrolizumab in the second half of 2020. I will now turn the call over to Dr. Edelman, who will discuss the significance of these results. Dr. Edelman?
Thank you. In my first slide, demonstrates the molecular subsets of lung cancer and how much the field has fragmented in the last few years. Within that slide, I also demonstrate some of the fact that even within subsets, as for example with RET, there are subsets of subsets. This has become an increasingly fragmented field. On my next slide, one can see that which compares a lecture slide that I had from 2005 with something from last year, which is already obsolete, that there's been an increasing number of options in non-small cell lung cancer.
While this is unquestionably great news for patients and their treating physicians, it has created a number of problems in developing trials as the patient eligibility for every trial requires a variety of criteria which were very different from what we had as recently as 10 or 15 years ago. In the next slide, I give an example of the current. This is pretty much a comprehensive overview of immunotherapy versus chemotherapy in first-line randomized trials. These studies, all of which have been presented, some fully published at this point, demonstrate that the use of immunotherapy in high PD-L1 patients is superior to standard chemotherapy. However, as can be seen, the overwhelming majority of patients will progress within approximately a year or less than that, and therefore there still is a substantial unmet need. Very few patients will have persistent efficacy beyond 30 months.
Therefore, even with the progress with immunotherapy, probably fewer than 3%-5% of patients are actually durable long-term responders. Similarly, for chemotherapy versus chemoimmunotherapy, the next slide demonstrates that even in this situation, the overwhelming majority of patients will progress, again, with very few long-term survivors. If you'll turn your attention on that slide to the first two trials, the KEYNOTE-021 cohort G and KEYNOTE-189, what I'm demonstrating in that is if you look at the control arms, the overall survivals drop into phase II from 20 months to 11 months and are there to simply indicate that between phase II and phase III, there can be considerable variability as one goes to larger studies. All early results need to be viewed with some caution.
What are the unmet needs, my next slide, in advanced non-small cell lung cancer. The benefits of immunotherapy alone or in combination are real but limited, regardless of what the PD-L1 or tumor mutation burden or any current biomarker would have. We have very few patients who are truly long-term survivors, i.e., beyond 36 months. The problem right now is we have several populations of patients and no clear definitions. There are those who are primarily resistant to the use of immunotherapeutics. There are those who develop resistance to therapeutics. Furthermore, there are those who relapse after receiving immunotherapy as part of the adjuvant treatment in stage 3, and what will likely develop in earlier stage of disease. If one looks at the curves there, this is from the KEYNOTE-189 study presented by Dr. Gandhi.
You can see from the green arrow there that there's a long way down from 100% to even the plateau in progression-free survival at approximately 18 months. Again, a clear unmet need in advanced non-small cell lung cancer. On my next slide, there are many potential targets and many trials that address these. We have a number of issues in the next generation of studies. We need clear rationale, and these days it's become a little bit like what we had many years ago with carboplatin and Taxol, where whatever your drug was added into that. We need clear evidence of mechanistic and preclinical synergy. There are questions of how to combine the drugs, whether they should be additive, sequential, or phased, and the specific population, whether naive, resistant, refractory, and whether there's intervening therapy.
Again, there are no formal universally accepted definitions for the resistant and refractory settings at this time. What do we need to know on what is promising? Well, in any situation, and at the time of the World Conference, I was addressing several studies. We need to look at the prior lines of therapy. For entinostat, there was prior immunotherapy as well as chemotherapy in many cases. We need to know what their activity was in specific context of TMB and PD-L1. What should the endpoints be in early studies? Because, again, this will depend very much on what their prior therapy and response was as well as the specific molecular and other characteristics. It's really unclear what should be considered as evidence of promise, whether it's response rate, progression-free, or landmark survivals.
It would be nice to have biomarkers for selection based upon good hypothesis or exploratory in the population. There are many practical issues of fragmentation of the population, too many questions and too many trials right now, and a rapidly changing landscape where trials are frequently becoming obsolete even before activation. How do we distinguish a trial to refer a patient in a competitive landscape? Therefore, a robust, easily obtainable biomarker is a definite plus and simplified on-study requirements. Most studies these days are requiring substantial tissue and other requirements. If one turns to the specific entinostat and pembrolizumab study, this was a phase II single-arm trial, but a substantial number of patients were actually resistant or refractory to the anti-PD-1 and PD-L1 agents, and many were treated, and even some demonstrated response immediately after progression with the anti-PD-1 or PD-L1 agent.
The monocyte high status appears to select for patients who obtain durable benefit. Seven of the eight patients who had 36 weeks or more of benefit were monocyte high, while 46 of 47 with low monocytes did not benefit. There were 12 of 19 with high monocytes did not benefit. The marker is not perfect. It does seem to be necessary but not necessarily sufficient. The test does have a good sensitivity, by my calculation, about 88%, and is very specific, 98%. The numbers are small with wide confidence intervals. In the planned approach, it will allow for some better assessments of this biomarker. This appears to be a very reasonable approach to enriching the population and enhancing the opportunity for success while minimizing the use of patient resources. Thank you.
Dr. Meyers. Operator, we'd like to now open the line for any questions people have about Dr. Meyers' presentation or Dr. Edelman's presentation on non-small cell lung cancer. Any questions for those two speakers only. We'll talk more about 2112 after.
Thank you. Ladies and gentlemen, if you have a question at this time, please press the star then the one key on your touch tone telephone. Again, if you would like to ask a question, press the star then the one key on your touch tone telephone. Our first question comes from David Lebowitz with Morgan Stanley. Your line is open.
Thank you very much for taking the question. In the low monocyte and the high monocyte populations, just in the typical patients at this stage, is there any breakdown of what the expected survival or how quickly it will take under a normal treatment for these patients to progress? I guess trying to create some sort of a baseline for how to look at these patients going forward.
Right. Maybe I'll take that question, David. Thanks very much. I think there is some data in the literature on the outcome of patients in this population treated with standard chemotherapy. There's not data in the literature on how that breaks out by high or low monocytes.
Okay. We don't really have a baseline to compare how these patients might do respectively on a purely controlled basis, high monocyte versus low monocyte.
That's right.
Yes. David, I would add, though, that high monocytes are classically considered to be a poor prognostic factor.
makes our data even more compelling.
Sure. Okay. Thanks for taking the question.
Thank you. Our next question comes from Chris Shibutani with Cowen. Your line is open.
Great. Thank you very much. Dr. Edelman, I was curious to know your thoughts, given the reference that you highlight, where the peripheral classical monocyte is identified as a predictor of clinical response to PD-1s. What would you expect upon PD-1 rechallenge in these high and low monocyte populations? I think one of the questions becomes what will the incremental benefit be for the combination with entinostat? Specifically then, what would you expect from a PD-1 rechallenge?
There are two different things here. The paper was in melanoma, and that had high monocytes as a predictive marker for the benefit from anti-PD-1 therapy. In the trial that was presented by Dr. Hellmann, monocytes were assessed, and this was a group where the patients did have high monocytes, and that's what was the predictive marker, and those patients had already, for the most part, progressed after an anti-PD-1 or PD-L1 agent. In this particular setting in lung cancer, that's where the marker was utilized and what had the predictive benefit.
I think, Chris, it's important to note that the majority of patients had received PD-1 as their immediate prior therapy, and that the median time to coming on to our trial was only about 2.2 months, so that it was almost as if entinostat was being added to a PD-1 antagonist in the setting of progression. Strictly speaking, it was not a rechallenge effect.
Thank you. Our next question comes from Robert Hazlett with BTIG. Your line is open.
Hi, this is actually Jake Colby on the line for Bert. Thanks for the question. I wanted to follow up on the comment that ESMO reinforced your belief in the entinostat-KEYTRUDA combination. Could you provide a little bit more detail around that? Secondly, I was wondering if you could provide any more details on the powering assumptions for PFS primary endpoint. Thanks.
Sure. I wouldn't say that ESMO reinforced or it changed our conviction around entinostat-KEYTRUDA as a potential therapy for these patients. I think what we heard from ESMO is what other competition is there. I think in my prepared remarks, I noted that our decision tree on which projects to take into registration trials depends on unmet need, depends on the competitive landscape, and depends on our ability to give a return on our investment. We think there wasn't really anything at ESMO that made us feel like, from a competitive point of view, we weren't in a really good position. In terms of the powering of the trial, I don't think we were not really at liberty to say just yet about what the trial is powered for. We'll do that in subsequent conversations.
Thank you.
Thank you. Our next question comes from Madhu Kumar from B. Riley FBR. Your line is open.
Hey, guys. Thanks for taking my question. A question for Dr. Edelman. In your experience, is there a material difference between patients who respond to a PD-1-containing therapy and then progress, versus patients who just kind of blow through the PD-1 therapy with no immediate response?
Well, in addressing this, it's essentially my personal clinic and it's anecdotal. Certainly the patients, there's also the people who had chemoimmunotherapy, which is where the field's moved to, versus those who received immunotherapy as their second line in the past. These are all evolving and changing populations. The patients who had gotten, say, immunotherapy in second line for the year or two where that was the big standard and the only place you could use it outside of a trial, patients who blew right through immunotherapy did not do very well. They progressed very rapidly and usually died very shortly afterwards. For the patients who have now been getting chemoimmunotherapy and then progress similarly, their outcomes are not good. In fact, it's been an interesting set of questions of where do you go, which chemotherapeutic should you use, et cetera.
There are some patients who, if they just blow right through whatever their frontline therapy is, they don't do well, and that's a historical truth. It was the same thing with standard chemotherapy in the front line. A patient who would progress rapidly through that did not respond well to docetaxel. The people who respond to subsequent therapies are basically the people who had benefit from the prior treatments. That basic truth has not, for the most part, really changed. For patients who have had some degree of benefit, many of them continue on, and that's obviously seen when you have, say, a PFS of 20 months or so and then an OS that's 30 or 40. Clearly, they've had benefit that comes from other things.
There does appear, I tend to believe that this is true, is there's probably some subset out there where immunotherapy tends to set them up for benefit from subsequent chemotherapy. There is a need for controlled trials in this because we're not really sure what happens in that group. As opposed to the use of cytotoxics, there are some persistent effects of the immunotherapeutics even after cessation. Does that address your question?
Yeah, you got to my second question. A question for the team. In the study, when you talk of patients who progress on PD-1 therapy, does that include patients who respond and then stop responding and patients who never responded to the PD-1 therapy? Do you stratify on those groups?
Madhu, just to clarify the question, do you mean for the next trial, ENCORE 607?
Yes, sir.
Again, we suspect, as Dr. Edelman's pointed out, that the field has pretty much moved to chemoimmunotherapy as first line. The vast majority of patients will probably get chemoimmunotherapy as their initial therapy. It's a little bit different than. Most of those patients will have either, as you said, they don't respond at all, and as Dr. Edelman said, those patients tend not to do well, or they've had a response. They're now on their maintenance pembro, and then they progress.
Yes. I'm asking for ENCORE 607. Do you include both of those as the patients who progress after response to PD-1 plus chemo and patients who never responded to PD-1 plus chemo but.
Yeah
You include both? Okay.
They're both eligible, right.
Do you stratify on those situations?
We haven't disclosed that yet.
Okay, thanks.
Thank you. Our next question comes from Joel Beatty with Citi. Your line is open.
Hi, thanks for taking the question. Question on the monocyte biomarker. Is this a marker that cancer physicians are familiar looking at and are already making treatment decisions based on, or will this be something new for them?
This will be something new for them. However, to Dr. Edelman's point, this is a very easy assay. It's a simple peripheral blood draw, and the monocytes can be counted easily and quickly, so there will be rapid turnaround by a validated laboratory at the time that the trial actually is initiated. We believe that this would be a strategy that could be easily adopted by the majority of medical oncologists, whether at academic centers or in the community.
Great. Is there a proposed mechanism of action on why patients with high or low monocytes might respond to different therapies?
Yeah. Maybe if I could ask Peter Ordentlich on the call. Peter, do you want to give a brief answer to that one?
Yeah, certainly. Yeah, it's actually quite interesting. We've been doing gene expression work on the tumor biopsies from the patients, both in the high and low groups, and it looks like we've identified gene expression pathways within the tumor that are associated with the monocyte levels and, in fact, give us insight into the mechanism of how the entinostat pembro combination may be working. It's actually pretty fascinating science. Hopefully, we can present it shortly.
Great. Thank you.
Thank you. Our next question comes from Ed White with H.C. Wainwright. Your line is open.
Hi, thanks for taking my question. Dr. Edelman had said that the trials right now are becoming obsolete before completion. Just with the last question, we talked about the monocyte biomarker being new, and doctors aren't familiar with it. I just want to ask about the enrollment and what you're assuming for enrollment. How many sites will be used, and are you confident that you're going to be able to complete enrollment in the fashion that you mentioned, getting data in the second half of 2020? Just what gives you confidence that that will be the timeframe? Thank you.
I don't think we're in a position to disclose the number of sites. Obviously, that is the result of a very intensive feasibility study that will be conducted as we initiate the trial. Suffice it to say that we will be tasked with including as many sites necessary as to be able to complete enrollment of the trial in rapid fashion so that the results will not, in fact, be obsolete. I think that's all we're at liberty to say at this point.
Yeah. I think the only thing I would add to Michael's comment is, I think, as Dr. Edelman went through, the field is pretty generally moving to chemo immunotherapy as first line. I think these patients who have progressed after chemo immunotherapy, there unfortunately will be large numbers of them available for treatment. The earlier question about what did we see at ESMO or World Lung in terms of emerging treatment for that population of patients, we actually think that we're probably in the lead there. I don't think that that standard of care is going to change during the time that we're enrolling this trial.
Okay. Thank you.
Thank you. There are no other questions in the queue.
Okay. Well, thanks very much for all the questions. Let me again thank Dr. Edelman for joining us today. I know he's very busy, and I hope you appreciate his perspective on the potential for entinostat to play a role in this emerging lung cancer treatment landscape. Now let me provide a brief commentary on E-2112. Slide 29 again summarizes the trial design. The trial has now randomized 605 patients to exemestane versus exemestane and entinostat, and there are two independent primary endpoints, PFS and OS. We now know that the PFS analysis did not meet the high bar for statistical significance, which would have provided us the earliest regulatory filing opportunity for entinostat in hormone receptor-positive breast cancer. We also know that the trial will progress as designed, having recently passed the third interim analysis for OS.
As we've noted before, OS analysis is done approximately every six months, and the next interim OS will be around May of 2019. The OS result could therefore be available within six months from now, or depending on the event rate and the treatment effect, may not be available until a subsequent OS analysis. Slide 30 is a reminder of the data that resulted in the FDA granting Breakthrough Therapy designation to the entinostat/exemestane combination for patients with hormone receptor-metastatic breast cancer who progressed on treatment with a nonsteroidal aromatase inhibitor. This slide shows the results for both PFS and OS from the phase II ENCORE 301 trial. The trial was positive for both endpoints, with the treatment effect appearing greater for OS than for PFS. Indeed, it was the OS observation that led to the Breakthrough Therapy designation.
I'd like to provide some additional perspective on the two primary endpoints of E-2112. Slide 31 summarizes this information. It's important to remember that E-2112 is primarily an OS trial. The Breakthrough Therapy designation that we received from the FDA was based upon the impressive OS results seen in our phase II trial. The hazard ratio that we observed for OS in phase II was 0.59. E-2112 has 80% power to detect a less impressive hazard ratio of 0.75, and E-2112 would be statistically significantly positive at a hazard ratio of 0.8. The type 1 error rate for OS is 0.048, which is basically the same as the standard 0.05.
We should contrast this to PFS, for which we saw a hazard ratio of 0.73 in phase II, yet E-2112 was designed to detect a hazard ratio of 0.58 and would have only been statistically significantly positive if the hazard ratio was 0.67 or lower. Perhaps most importantly, the type 1 error rate for the PFS test was 0.002. Based upon the phase II data and the design of the trial, OS is considerably more likely to be positive than PFS. Indeed, we remain very confident that E-2112 will be a positive OS trial. Let me now summarize where Syndax is today. As I noted in my introductory comments, slide 32 depicts the series of phase II trials we have undertaken to examine the potential of entinostat to enhance the efficacy of PD-1 antagonists.
Today, we've described the final phase II data from the cohort of non-small cell lung cancer patients who have progressed on both chemotherapy and a prior PD-1 antagonist, we've described our plans for further development. The European Society for Medical Oncology was held last week in Munich, we've reviewed the relevant clinical data presented at that meeting, as well as data from other recent scientific congresses. We remain incredibly enthusiastic about the data we've just reviewed with you, we believe we are actually very well positioned to capitalize on our leadership position in non-small cell lung cancer. I want to again repeat the two key points I made earlier. As designed, our planned registration trial can both validate the classical monocyte biomarker and demonstrate that the combination therapy of entinostat plus KEYTRUDA is superior to standard of care chemo in the high monocyte population.
The trial is very efficiently designed and will enroll approximately 200 patients with data potentially available within two years, the second half of 2020. This could position us to be the first novel therapy with full regulatory approval both in the U.S. and E.U. in this sizable population of patients and would be our second significant launch in the next few years following on the heels of a breast cancer approval. As indicated on slide 33, we also have two randomized phase II trials enrolling approximately 200 patients, reading out over the next six months, one in triple negative breast cancer and one in ovarian cancer. Now that enrollment is complete in E-2112, we look forward to the OS data with two interim OS readouts scheduled for 2019. In addition, we remain on track to file the IND for our Menin program in the first half of 2019.
We believe we have numerous programs with which to build value for our shareholders. With that, let me open the call to any additional questions that people might have.
Thank you. Ladies and gentlemen, if you have a question at this time, please press the star, then the one key on your touch-tone telephone. We have a question from David Lebowitz with Morgan Stanley. Your line is open.
Thank you very much for taking my question again. With respect to the OS analysis that recently occurred, I'm assuming that there's not only the ability to stop the trial based on efficacy, but what's the threshold, I guess, to stop it based on futility?
Michael, you want to take that one?
David, there clearly are futility analyses at the time of each interim analysis for overall survival. The boundaries are actually for both efficacy and futility are driven by the number of events which occurred at the time of the analysis, and I don't think it's been publicly disclosed by the ECOG-ACRIN DSMC as to what the number of events is at that time. What I would tell you is from knowing the trial designs, that clearly if there were no benefit in terms of overall survival, that would have triggered a positive futility result.
Okay. Thank you for answering that question.
Thank you. We have a question from Joel Beatty with Citi. Your line is open.
Hi. Thanks for taking the question. I see that the trial is 80% powered to detect a hazard ratio of 0.75 on overall survival. Could you just discuss how to think about that in light of the multiple interim analyses that are occurring? Is each interim powered for that or is that just the final analysis and then the interims are less?
Joel, the way the trial is designed is there's 80% power for the 0.75 and the minimum hazard ratio that would be statistically significant is 0.8, which would translate based upon the assumptions of the trial to about a five-month improvement in overall survival. There is a small amount of alpha that is spent at each one of the interim analyses. Again, I don't think the ECOG-ACRIN DSMC has discussed what that small amount of alpha is that's spent, but it's relatively minor.
Great. Got it. Could you remind us what triggers the final OS analysis and when is that expected to happen?
The final OS analysis is at 410 events, this is of course an event-driven trial, we don't know exactly when those 410 events will occur. Based upon modeling that we've done, we think that those full 410 would probably be the analysis in November of 2019, although it could drift into 2020.
Got it. Thank you.
Thank you. Our next question comes from Madhu Kumar with B. Riley FBR.
Yeah, thanks for taking my question. On that point on kind of model timing for the OS readout, does that account for some fraction of patients having now previously been on CDK 4/6 inhibitor therapies? This is a difficult question because I know earnings are coming up, but kind of back of the envelope based on your cash runway, thinking about both 2112 and ENCORE 607, based on the kind of previously described cash position you guys have, with those trials kind of ramping up and continuing, what is the kind of cash runway for you guys?
Yeah. Madhu, I think the question about the cash runway, we actually will go into that in some detail on our next quarterly call, which will be coming up fairly shortly. We'll pass on that question for now. I think the question of the timing, remember that when the trial started, there were probably a fair number of patients who did not have a CDK 4/6 before they came into the trial. At the later stages of the trial, more and more patients actually had already received a CDK 4/6. I think this question of the timing of when the final 410 events would occur, the modeling tries to take that into account, but that's where I think there's some uncertainty about exactly when that final 410 will occur.
Okay. Remind us, do you stratify on previous CDK 4/6 therapy?
No.
Okay. Well, thanks very much.
Thank you. If you would like to ask a question, press the star, then the one key on your touch-tone telephone. We have a question from Chris Shibutani with Cowen. Your line is open.
Great. Thank you very much. Apologies. I wanted to go back to one quick question on the lung trial, 607. You describe it as a proposed trial. Can you just remind us if you've had any interactions with the FDA to discuss this as a potential registrational trial? As a second follow-up, in terms of the total patient population number, comment a little bit further, I think you may have mentioned a little bit about the sizing of this study that you've selected here. A little surprised that it maybe isn't a little larger. If you could just remind us the FDA and then the trial size. Thanks.
Right. Chris, I think the slides have the actual patient numbers per arm, so it's just less than 200 patients. Again, someone else had asked about the detail powering. We won't go into that on this call. We can talk about that some other time, but it's sufficiently powered, we believe, to show both that the monocyte is valid and that the high monocyte population has a better PFS than the patients with standard of care. We have had discussions with FDA about this trial design.
Great. Thank you.
Thank you. I'm showing no further questions at this time. I'd like to turn it back to management for any closing remarks.
Sure. Thanks very much, operator. Again, let me thank everybody for joining at such a short notice. We appreciate your attention. Again, I just want to emphasize two points. One is that we remain quite positive on the possibility of E2112 being a positive trial. I don't think any of us who understand the design of the trial in the phase II are all that surprised that PFS didn't hit. We had always had that as our best-case scenario, and we were prepared to file should PFS hit. Given the statistical hurdle that had to be passed, it's not that surprising that it wasn't positive, and yet we remain quite positive on PFS. I mean, on OS.
Secondly, I would say is, back to the earlier question, the treatment of patients who have progressed on chemo immunotherapy is really an area of high unmet need and an area of emerging population of patients. We think we're in a very good position with ENCORE 607 to potentially bring an important new option to those patients. We're excited to get that trial underway. I'm glad somebody asked pointedly to Michael Schmidt, how are you gonna get it done on time? We have great confidence in our clinical operations team. They always deliver for us, we're quite excited about getting that trial underway. Thanks again for everybody for joining the call, and we look forward to further discussions.