Hello, everyone. For those of you who don't know me, I'm Bill Doyle. I'm the Executive Chairman of Novocure, and I'd like to welcome everyone who's in the room today and also everyone who is participating via the webcast to the very end of ASCO 2023, for our investor session to discuss the results that we disclosed today of the LUNAR trial in non-small cell lung cancer. I want to start and say, notwithstanding the initial market reaction, which of course we're all cognizant of, this is a critically important day for Novocure. 23 years ago, Novocure was founded to take advantage of a brand-new approach to fighting cancer. We always start these talks by reminding everyone that we're a physics-based modality. We treat cancer using electric fields.
Electric fields are forces that as gravity exerts forces on masses and as magnetic fields exert forces on ferrous metals, electric fields exert forces on charged components of cells and allow us to push and pull on those components in order to disrupt many cell processes. In the early days, we focused exclusively on the effect on mitosis, where electric fields prevented mitotic spindle formation and resulted in cancer cell death. In the now, 23 years of preclinical and clinical research, we've learned much more about what these forces, in fact, do inside cells, and that research has led us to further understand the broad applicability of the platform.
We know that any place in the body where we can create an electric field of a therapeutic intensity, and that's an electric field of 1 to 3 volts per centimeter, we can tune those electric fields to enter target cancer cells. When they enter those target cancer cells, they create cancer cell death, cancer cell stress, immunogenic cell death, and allow a number of different strategies beyond just combination with chemotherapy, but combinations with not only standard of care chemotherapies, but new chemotherapies in particular indications. In exciting new research and research that we're going to describe in phase 3 data today, combinations with immunotherapy and other combinations, PARP inhibitors, radiation, all of which we are now exploring in subsequent clinical trials. It's my great pleasure today to be the person to introduce the agenda.
We're gonna start, and I'll introduce the participants up here on stage in a minute, but we're gonna start with a presentation of the LUNAR data, the same data that were presented earlier this morning at ASCO. We're gonna leave plenty of time for Q&A, so that everyone can have a chance to ask your questions, particularly of the key opinion leaders who are joining us today. Again, I couldn't be more pleased to introduce the first author of the study, Dr. Ticiana Leal from Emory. She did a magnificent job earlier today presenting to the assembled crowd at ASCO, and the senior author on the abstract, Dr. Corey Langer from UPenn.
Someone that if any of you are familiar with the progress that's been made in lung cancer over the last decades, you know that Corey has been at the center of these advances. Our MC is our own Pritesh Shah, and he will be guiding the Q&A. With no further ado, I'm gonna turn the clicker over to Dr. Leal.
Thank you. Okay, so here's a redo of our ASCO presentation today from our oral abstract session. An honor to present on behalf of my co-authors, the Tumor Treating Fields therapy with standard of care in metastatic non-small cell lung cancer after platinum-based therapies, a randomized phase 3 LUNAR study. Metastatic non-small cell lung cancer remains largely incurable. In patients with metastatic non-small cell lung cancer without a driver mutation, platinum-based chemotherapy and immune checkpoint inhibitors are standard frontline therapy. However, most patients develop disease progression, and 5-year survival is only 9%. Treatment options that extend survival beyond progression are limited. Current approaches include chemotherapy, mainly docetaxel, plus minus ramucirumab or immune checkpoint inhibitors for eligible patients. There remains a high unmet need for new, effective, and well-tolerated therapies for patients in the second line and beyond.
Tumor Treating Fields are electric fields that exert physical forces on electrically charged components and have been shown to disrupt mitosis in cancer cells. Under TTFields, this disruption of mitosis leads to aneuploidy and induction of endoplasmic reticulum stress. Downstream effects include immunogenic cell death, triggering a systemic anti-tumor immune response. Preclinical evidence has demonstrated the activity of TTFields with immune checkpoint inhibitors or Taxanes. On the left-hand corner, you're seeing the combination of TTFields plus paclitaxel versus paclitaxel alone, demonstrating decreased cell viability in non-small cell lung cancer cell lines. In the right-hand panel, the combination of TTFields and anti-PD-1 in tumor-bearing mice led to greater reduction in tumor volume compared to control or either modality alone. TTFields therapy is a non-invasive anticancer modality. The electric fields are generated by a wearable medical device and delivered to the chest, to the tumors by two pairs of arrays.
The device is delivered to the patient at their home by a device support technician who provides education for the patient and their family, and it is recommended for continuous use. TTFields therapy is currently approved in glioblastoma and malignant pleural mesothelioma. Prior to the LUNAR study, a pilot study demonstrated the safety and the feasibility of TTFields therapy with pemetrexed in advanced non-small cell lung cancer. The LUNAR study is a randomized phase three global study designed to evaluate the safety and efficacy of TTFields with standard of care, compared to standard of care alone in patients with metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy. 276 patients with ECOG performance status of 0 to 2 were randomized 1-to-1 to TTFields therapy and standard of care, which contained investigators' choice of immune checkpoint inhibitor or docetaxel versus standard of care alone.
Patients were followed every six weeks and continued therapy until progression or intolerable toxicity. The data cutoff was November 26th, 2022. The study was conducted in 124 sites in 17 countries. The primary endpoint of the LUNAR study was overall survival, with TTFields plus standard of care versus standard of care alone. Key secondary endpoints include overall survival in ICI and docetaxel-treated subgroups. Other secondary endpoints include progression-free survival, overall response rate, progression-free survival, and overall survival by histologic subtypes, quality of life, and safety. The LUNAR study targeted a hazard ratio of less than 0.75, using a two-sided proportional hazards testing with an alpha of 0.05 and a power of 80%, stratified by standard of care treatment and histology. Key secondary endpoints were tested hierarchically if the primary endpoint was met.
In a planned interim analysis in March of 2021, the Data Monitoring Committee recommended that a reduced patient accrual of 276 and a follow-up of 12 months would be sufficient to evaluate endpoints of safety and efficacy while retaining statistical power. The baseline demographics and patient characteristics were similar across all subgroups. The median age was 65. The majority of patients were male. The majority of patients were White, 80%. 30% of piece were enrolled in North America, West Europe, Eastern Europe, and 9% in East Asia. The majority of the patients had ECOG performance status of 0 to 1, and 84% of the patients were current or former smokers. 56% of the patients had Non-Squamous histology.
With regards to PD-L1 expression, about 17% of the patients had PD-L1 expression, less than 1%, 29%, 1%-49%, and 13%, 50% or greater. About 45% of the patients had unknown PD-L1 status. With the PD-L1 status available, there were no differences between the subgroups. 89% of the patients had 1 prior line of therapy, and about 10% of the patients had more than one prior line of therapy, two or more. 31% of the patients had prior immune checkpoint inhibitor, and about 30% of the patients had a response to their prior therapy. 16% of the patients had baseline liver metastasis. The LUNAR study met its primary endpoint of overall survival.
The median overall survival is 13.2 months in the TTFields plus standard of care, versus 9.9 months in the standard of care arm, with a hazard ratio of 0.74 and a P value of 0.035. The curve separated early and remains separated throughout. The hazard ratio here met statistical significance for our patients. The overall survival in the ICI-treated patients was particularly prominent, with a median overall survival of 10.8 months in the ICI-treated patients to 18.5 months in the TTFields plus ICI, with a hazard ratio of 0.63 and a P value of 0.03. The three-year survival rate is 27% in TTFields plus ICI, versus 9% in the ICI alone group.
The median overall survival in TTFields plus docetaxel was 11.1 months versus 8.7 months in the docetaxel, with a hazard ratio of 0.81 and a P value of 0.28. The median overall survival in the non-squamous subgroup was 12.6 months in the non-squamous group with TTFields plus standard of care, versus 9.9 months in the standard of care alone, with a hazard ratio of 0.8 and a P value of 0.28. The median overall survival in the Squamous subgroup was 13.9 months in TTFields plus standard of care, versus 10.1 months in the standard of care alone, with a hazard ratio of 0.67 and a P value of 0.05.
The median PFS was 4.8 months in TTFields plus standard of care versus 4.1 months in the standard of care, with a hazard ratio of 0.85 and a P value of 0.23. The overall response rate was 20% in TTFields plus standard of care versus 17% in the standard of care arm. The majority of patients achieved stable or response to their therapy. We observed five complete responses, all occurring in patients receiving an ICI, four with TTFields therapy and one with ICI alone. Analysis of patterns of progression in-field versus out-field is ongoing. The majority of patients had at least one adverse event, not necessarily related to study treatment.
The rate of grade three or higher adverse events was comparable between the two groups, 59% in TTFields plus standard of care versus 56% in the standard of care arm. One notable difference was dermatitis, seen in the TTFields plus standard of care, 43% all grades. Other frequent adverse events were attributable to systemic therapy or underlying disease. No difference in rate of pneumonitis or other immune-related AEs were observed. Any serious AE reported was 53% in TTFields plus standard of care versus 38% in standard of care. AEs leading to discontinuation included 36% in TTFields plus standard of care versus 20% in standard of care. Any AE leading to death was 10% versus 8%, respectively. There were no notable differences in health-related quality of life when TTFields therapy was added to standard of care.
Detailed analysis is ongoing. The median device usage was 15 weeks with ICI and 13 weeks with docetaxel. Any adverse device effect was seen in 73% in the TTFields plus ICI and 70% in TTFields plus docetaxel. Most device-related effects were grade 1/2 dermatitis. Dermatitis resolved in 87% of the cases, with a median duration of three weeks. There were no grade four toxicities and no deaths attributable to TTFields therapy. In conclusion, the pivotal phase 3 LUNAR study met its primary endpoint of overall survival. TTFields therapy with standard of care provided a statistically significant and clinically meaningful 3-month improvement in median overall survival versus standard of care, with no added systemic toxicities. Statistically significant 8-month increase in median overall survival was demonstrated with TTFields therapy and an ICI.
There was a 2.4-month difference in median overall survival for TTFields therapy and docetaxel versus docetaxel alone. TTFields therapy should be considered part of standard of care for metastatic non-small cell lung cancer following progression after platinum-based therapy. Additional studies evaluating TTFields with current standard of care for first-line metastatic and locally advanced non-small cell lung cancer are underway. In summary, TTFields therapy is a potentially paradigm-shifting new treatment modality. I'd like to thank our participating patients, their families, and clinical research teams for your commitment and contributions, and I'd like to thank our sponsor, Novocure. Thank you very much.
Thank you, Dr. Leal, congratulations to you and the entire lung cancer community on this study. We're now going to shift to Q&A. It's my honor to be facilitating this session. I know many of you today have questions about the data set, some things that we've already heard about and some things now that you may be thinking about as you've seen this data set presented by Dr. Leal. I'm very excited to be facilitating this session. Before we turn it over to the floor, though, there are a few categories of questions that have come through, and we'd like to start with that. Let's get to the heart of the matter related to this data set.
When you see the clinical characteristics of any study, one of the first questions that comes up is: Is there a balance in the study arms? One of the questions that's coming up around the LUNAR data set is related to the PD-L1 status and the balance of the PD-L1 status between the treatment arms and then the subgroups of the treatment arms. I'd like to ask you this question, if you can comment on how you think about it, and is the data set complete in this regard, and how do you think about the PD-L1 status? I'd like both of you to be able to address that from your respective perspectives.
With the available PDL-1 data that we have, there were no imbalances between the groups. There were no imbalances between the subgroups. In that regard, I think, you know, we're pretty set on that. The additional thing that I also think about is within the ICI-treated subgroups, 63% had PDL-1 expression of 1% or greater, which is consistent with what we would see in real-world data.
I know there was some speculation that the wide divergence in the ICI group might have been due to an imbalance of 50% or higher PD-L1 expression, but that was clearly not seen. I guess the other concern, I know this has been brought up and may be asked later on, is why were so many not measured? You gotta remember, this study started at a time before PD-L1 testing was standard. Certainly, it's never really been standard in the second line.
Great. Thank you very much. The second question that comes up is related to the study design itself. Now, in oncology, we're used to the standard of care evolving as trials are going on, and that's certainly what we saw happen here. Can you comment on the shift in standard of care? As you look at this data set now, and as you think about your patient population in the second-line setting, how will you sort of, how will you put into context the results from the LUNAR study and the patient that's sitting in front of you that may be eligible for Tumor Treating Fields therapy, whether that's added on to an immune checkpoint inhibitor or docetaxel?
Yeah. I think, you know, this study really addresses a population, that has limited therapy options in second line and beyond. For a patient in second line and beyond, I think of patients that I'm rechallenging with an ICI, and I see this as a strategy that specifically with the ICI-treated groups, that is still sensitive to immune checkpoint inhibitors without any added toxicities. I would certainly feel very comfortable in adding TTFields to immune checkpoint inhibitors. I think also with docetaxel, you know, when we think about our approval for docetaxel ramucirumab in 2014, based on the REVEL study, when you think of the median OS there, the median OS for docetaxel is 9.1 months.
The median with ramucirumab is 10.5 months, and here we have a median survival that is comparable and numerically slightly better, again, without added toxicities. If you look at the toxicities for ram, that certainly is something that is not for every patient. I think acknowledging that there is a shift in the, you know, front-line strategies as we were conducting the study, I think this data is relevant to our patient population, and I do think it really fills in a gap for our patients in second line and beyond.
I can only amplify those comments and further say that this is the first positive trial we've seen in six and a half, seven years in this setting, in the second-line setting, since the advent of the checkpoint inhibitors in second line. I'm gonna address the elephant in the room, which is Rebecca Heist brought this up during the discussion. I know this has already been asked. Isn't the standard of care changed, that docetaxel is the de facto standard of care, and certainly the differences in the curves was not pronounced there as it was for ICI? That standard of care is in constant evolution.
Many of you may not be aware of a trial called S1800A, which is a randomized phase 2 effort done through the NCTN, the cooperative groups that Ticiana and I are both part of, that compared checkpoint inhibitor plus Ramucirumab. Essentially, checkpoint inhibitor second line after prior platinum and checkpoint inhibitors, essentially the same setting, versus, quote, unquote, "standard of care alone," which was docetaxel. Frankly, majority were docetaxel and Ramucirumab, and that study showed that the checkpoint inhibitor in the second line after prior exposure to checkpoint inhibitor had a 3.5, 4-month improvement in median survival, and that's laid the groundwork for a major phase 3 trial that's gonna compare those approaches.
The notion that docetaxel is the, quote, "standard" and as fixed as the standard, I think is fallacious, is a constantly evolving standard, and I really think, particularly, given the results that Ticiana has shown, that this trial may actually have even further relevance as time goes on.
Great. Thank you very much for that. I'm gonna stay with this topic for a little bit more and dive into a very specific patient population, a question that keeps coming up, and that's related to those patients that were treated with ICI in the first-line setting in the ICI plus Tumor Treating Fields therapy arm. There were 3% of patients that were retreated. In that patient population, how do you think about your patients in the second line that will present to you in the clinic? Will you consider, and your peers consider, Tumor Treating Fields therapy for that patient population?
Yeah, and I think that's a patient population that I would certainly consider TTFields. We have clinical trial data with that. The KEYNOTE-024 data that used Pembrolizumab in first-line, that established the use of first-line Pembrolizumab. In that data set, they actually have a subset of patients that were rechallenged upon progression after they completed Pembrolizumab monotherapy for two years and then had progression. We saw there that the rechallenge was a successful strategy and led to activity in those patients. However, that benefit the second time around was less pronounced, and here we have the option of adding TTFields, showing that differential improvement in survival there with TTFields plus ICI. I definitely would strongly consider that for a patient in that setting.
I've shared with you some trial data, my own personal clinical data. I would guesstimate about a third of my patients continue ICIs beyond progression. They may have Oligometastases, you know, limited number of sites or smoldering progression, so this is the perfect opportunity to graft a new modality onto the checkpoint inhibitor, which in my case, is almost exclusively Pembrolizumab. Tiziana and I are both involved in multiple studies in the second line, basically looking at other Immunotherapeutics, again, grafted onto the front-line checkpoint inhibitor.
Great. Thank you. I'd now like to open up the floor to the audience. If there are any questions here... I see a hand right there. Can we get the microphone over there, please?
Hi. You know, because this is a novel therapy, consistency and no outliers are important. In the phase 1, phase 2 trial, with TTFields plus .
... Pemetrexed, survivorship was 57% at one year. In this trial, you know, you clearly didn't get, you know, the control arm was about what you'd expect, between 30%-40%. Why didn't the docetaxel arm work?
I don't know that it didn't work. I think the primary endpoint of the study was met. The primary endpoint of the study was overall survival in the ITT population, which included the docetaxel-treated subgroup. Clearly, it didn't meet statistical significance. I think we need to do further deep diving into the data to better understand it. I think even within the data that we saw, I do see, you know, that there is a benefit there. However, we need to understand if there are subsets there that we're just missing.
It's a small study, the initial phase 1, phase 2, and as you're well aware, the therapeutic landscape is full of studies where the phase 1, phase 2 data don't necessarily match what we see in phase 3. I'm not terribly surprised, but we still see a numerical advantage that's in double digits. I agree with Ticiana. I think we need further analysis. We need to look at the nature and of response, depending on whether it's in-field or out-field, and that's being looked at. I view early-stage studies really as hypothesis-generating and not as definitive.
Great, thank you. There was a question up front here. We can pass the microphone again.
Hi, this is Nasim from J.P. Morgan, in for Jessica Fye. I have a question on the median PFS data that we saw. In light of the OS benefit, but similar median PFS between the arms, were patients treated with TTF beyond progression? Then, as a follow-up to that, like, what were the therapies used post-progression, and were they balanced? Thank you.
Great question. You're asking the PFS? Can you repeat the question about the PFS?
You're talking about the lack of significance in the PFS?
The PFS was similar between the two arms. That discordance with OS is something that we've seen before in other phase 3 trials that have looked at Immunotherapy, including CheckMate 057, KEYNOTE-010. I think ultimately, in phase 3 trials, the overall survival is the gold standard endpoint, and here we've met the overall survival. Regarding Tumor Treating Fields beyond progression, the answer is yes, there were some patients that did receive TTFields beyond progression that were allowed to continue on if they did not have in-field progression, but had out-field progression. We're still analyzing those numbers, and we'll provide more clarity once that analysis is ongoing.
I think you asked also about treatment beyond progression, and I think that's also.
Yeah, the post-treatment progression. About 25% of the patients received treatment, post-progression on this study. There were no imbalances between those groups. The majority of patients actually received docetaxel or gemcitabine.
I just want to remind everyone, CheckMate 057 was one of the positive phase 3 studies in the early ICI era in Non-Squamous that compared Nivolumab to docetaxel. The same general theme, PFS, no benefit, OS, clear benefit. We've seen that not just in non-small cell, but in Mesothelioma, where Ipi-Nivo seems to have an advantage over standard Chemotherapy. No response, no PFS benefit, clear OS benefit. There's nothing more definitive than survival.
Let's see if the microphone's coming.
It's just a couple for me. Larry Biegelsen from Wells Fargo. Congratulations on the.
Thank you.
on the study results. The squamous versus non-squamous discrepancy, everybody's asking about some of the discrepancies. I'll ask that one. Dr. Langer, from your experience, if it works on top of Immunotherapy, Tumor Treating Fields, in second line, how likely is it to work in the front-line setting if it were studied there? Just lastly, for Novocure, can we get an update on your front-line non-small cell lung cancer strategy, please? Thank you.
Yes, sure. We'll start with the histology question first, then we can go to Can the data translate into first line? Then I'll close it off with your question related to our development program.
With regards to histology, you know, there were no differences there. I don't know that there was not a comparison between non-squamous and squamous. I don't think there's a discrepancy between the groups, if that's what you were asking.
[audio distortion]
The Squames definitely had a greater advantage.
Yeah. The P value there was 0.05, we didn't compare the two groups.
I think what we ultimately need to do is suss out to what extent the Squames were Intrathoracic versus Metastatic. Again, we're gonna have a patterns of failure analysis and, you know, look at in-treatment versus outfield, infield versus outfield responses. That may give us some of the hints why there may have been a difference. On the other hand, it could have been serendipity. I'm particularly enthused about combining this with checkpoint inhibitors, both in front line and in locally advanced. Those studies are ongoing. Remember that our standard of care in treatment-naive, wild-type non-small cell, those without oncogenic drivers, is for 50% or higher Pembro alone, or KEYNOTE-189, pem/carbo with Pembro.
Here we have data in the second line, particularly with ICI, showing a benefit on. I'm quite hopeful that it will translate into frontline. In locally advanced, basically the same principle. Our standard of care now in patients who are eligible for immune checkpoint inhibitor is concurrent chemoradiation, followed by durvalumab. We're gonna be looking at the same question as well, durva, plus or minus Tumor Treating Field. If anything, the phase 3 data in the second line reinforce the leads and the hypotheses that will be looked at ultimately probably in bigger studies, both the frontline metastatic and locally advanced.
Great. I'm gonna circle up on the histology question just to make sure nothing is left to interpretation. When a patient's sitting in front of you in clinic, and they either have squamous histology or non-squamous histology, will you make a decision on whether to use or apply Tumor Treating Fields plus docetaxel or immune checkpoint inhibitor based on their histological status?
Both patients would be eligible for TTFields with systemic therapy.
Right.
I wouldn't make a difference based on the histology. Our data doesn't support that.
Well done.
For all comers.
Thank you. I will address your question. You're gonna hear at the end of this session around our development program. The only thing that I will say is the strength of this data set further fuels our long-term development in lung cancer. There are several studies that are planned, including taking this now, the benefit that we see in the second-line setting and bringing it in the first-line setting in the locally advanced disease. You'll get more information about this in moments to come.
Hi. Thanks so much. Jason Bednar with Piper Sandler. Doctors Leal, Langer, you're both clearly supportive of TTFields and use in second-line patients, eligible second-line patients. My first question here, I guess, revolves around really the third question that Pritesh was asking: Just how do you think the clinical community will evaluate the use of TTFields plus ICI as a second-line option, given that the trial population only had 2%, 3% of patients that were treated with an immune checkpoint inhibitor in frontline, but standard of care today currently requires or often uses immune checkpoint inhibitors as a frontline? I guess simply, do you think the lack of ICI use in frontline for the TTFields population will matter or inhibit clinical uptake?
I think, you know, when we think about real-world studies in second and third line, and you use like, you know, claims data or use, real-world data, the studies that I've seen in second line and beyond, after chemo immunotherapy, people are kind of all over the place in what they're selecting to use because docetaxel is ineffective and toxic. You really see that people are really trying to switch PD-1, PD-L1, add CTLA-4. You know, they're doing a lot of different things, and there's no, in the real world, clear standard second line and beyond therapy. I think the reality of it is everybody has tried as best as they can, continue their patients on an ICI for as long as possible if they're benefiting from it.
In the rechallenge setting, I think in real world, I think this is a strategy that I really do think that clinicians, given how well tolerated it is, no negative impact on quality of life, would go ahead and use TTFields with ICI, given the benefits and given the lack of other really effective therapies. You know, the duration of response with docetaxel is really short, and the toxicities are high. My answer is yes, I think clinicians will use it. I think people are excited about new treatment modalities, and I think patients are excited about things that are gonna help them and are really, you know, interested in novel therapies. I think it's a matter of educating, you know, the clinicians as we get out there and talk about this new technology, this new treatment modality.
Particularly as a modality that does not exacerbate systemic toxicity. I think that came through loud and clear. Obviously, a patient who's treated front-line, say, with KEYNOTE-189 and has disease progression within 3-4 cycles with rapid systemic relapse, we're not gonna expose that person to a checkpoint inhibitor. It's not clear that anything works in that setting. If they've had at least stability or response, they're out six months or nine months to one year, their disease is smoldering but clearly progressing, they're the perfect candidates.
Sorry, maybe just to follow up on the question. It's more so the lack of the use of ICI in the frontline for the TTFields population, where I'm wondering if clinicians will look at this and say, "We need more data. We need a follow-up study" where ICI use in frontline is followed up with ICI use of rechallenge with TTFields. Is that gonna be a requirement for the clinical community to drive uptake?
Of course, I'm just guessing, and I would say, given the patterns that I see in real-world data for second line and beyond, I would say no. I do think it's important to get more data in that patient population, and I hope that we conduct more studies in that patient population.
I think what's gonna happen, particularly as we see studies going forward, is that it'll be. I don't know if it'll be a stratification, but it'll be allowed in the context of additional trials. You'll probably get that answer, at least in part because arms of the studies will be balanced. Whether it's ICI plus some other modality versus, you know, docetaxel alone, again, it'll be reinforced. I don't see how once, assuming it gets an approval, that it can be accessed out of prospective follow-up clinical trials.
Okay. All right, thanks. The TTFields or the trial discontinuation for the patients in the TTFields plus, or in the experimental arm, I mean, that was higher than kind of the standard of care population it looked like. It was a pretty wide delta. Are you able to elaborate on maybe what drove that discontinuation in that patient population?
I think we need to do further analysis of that data.
... I'm not sure I completely understood your question?
The rate of discontinuation.
The rate of discontinuation.
What drove discontinuation?
Any hypotheses, I mean, without further analysis?
Median duration was about 15 weeks or 13 weeks for the two groups.
Yeah.
There'll be multiple analyses looking at duration as well as the daily duration. you know, it's been done with GBM, looking at the number of hours per day and outcome. Those data are still being analyzed.
Okay, thank you.
Any more questions from the audience?
Hi, Emily Bodnar from H.C. Wainwright. I was wondering if you can comment at all about compliance of actually wearing the TTFields among the different groups. A question for the company. When submitting the PMA, are you looking to just focus on TTFields in combination with checkpoint inhibitors, or do you still think there is potential for approval broadly in the second-line setting?
Regarding adherence and average use of device, you know, we're looking at that in the first three months and also, you know, average use during the hours. Currently, we don't have that data fully analyzed, but I do think that this will be important given that we've seen an association in GBM with that use and then outcomes. That is something that we're certainly very interested in looking at.
This is gonna require, obviously, a fair amount of teaching and servicing of our nurses, and advanced practitioners and frankly, the families. You know, families can control only two aspects of their loved one's lives: their dietary intake and, to some extent, their environment, and certainly what they wear as part of that environment. This actually gives them a certain degree of agency that they don't have when we're giving systemic agents.
As to your question related to the regulatory process, the study overall, the ITT population was positive. That will guide our regulatory approach and the label that we seek. Yes. Can we get the microphone up here, please?
Thanks for taking the follow-up. Just the two for me, for the clinicians. One, have you guys done a per-protocol analysis? I assume a per-protocol analysis instead of intent to treat. I assume that would be better, given the discontinuation rate was higher on Tumor Treating Fields. Second, I know you touched on this a little bit, but without there was no progression-free survival benefit, no overall response rate, stat six. The question that was emailed to me is the overall survival benefit driven by what patients got post the study? Thanks.
Well, the overall survival and the discordance between the overall response rate in PFS is what we've discussed previously, that we've seen that discordance before in these therapies with ICIs. I would say that given the fact that most of the patients who received post-progression therapy was docetaxel gemcitabine actually has no survival benefit defined in non-small cell lung cancer. you know, I think we need to learn more about this study and these data, gemcitabine and docetaxel is what they got after. I don't know that the post-progression therapies necessarily are driving that survival with the information that we currently have.
What you saw today was an intent to treat analysis, not per protocol. Pretty much they matched. I mean, there wasn't that much deviation.
Dr. Leal, can you comment on the balance between those patients in both arms that re-received post-progression therapies? I think you commented on that earlier.
Yeah.
That data point may be important.
I think it's also important to note that it was just a quarter of patients who got therapy post-progression, which again, I think highlights the need to incorporate new therapies as soon as we have them available so that patients can benefit. Like, I definitely agree that having the frontline studies and the locally advanced studies are gonna be very helpful addressing the rechallenge population, but for a patient living with lung cancer now, I think this is their time, right? If you see that benefit, we have a phase three positive study. People are living with cancer, and they want a therapy that's novel and better. I mean, I think that this study meets those gaps. We just have to follow up on all these important questions.
Great. Thank you. Next question. There's a hand up in the back.
Hi, this is Kevin here on behalf of Vijay from Evercore. Just to the clinicians, why would the PFS and overall survival dynamic seen in IO trials be relevant here when TTF is a local therapy, given both arms had the same IO?
I think, you know, one of the mechanisms of TTFields is, as we were talking about, triggering a systemic antitumor immune response. TTFields is delivered local regionally, but we think that perhaps there's systemic effects there, given the potential to trigger an antitumor immune response. Within that would be one hypothesis of driving that discrepancy.
There may be differential effects, both in-field and out-field, that may also be describing driving the discrepancy. There are other effects going on here that, frankly, semi-objective, really subjective OR and PFS don't necessarily catch. Gotta remember, in ICI-treated patients, we actually have Pseudoprogression in anywhere from about 5%-8%, and yet, we have data, for instance, from the OAK trial, which is another one of the critical phase 3 trials, comparing Atezo to docetaxel that showed treatment beyond progression in that group. Translated into survival benefit, as opposed to just switching. So there's a lot still going on that we haven't really figured out in the field of Immunotherapy.
Great. I don't see any more questions, so we are going to wrap up. I'm going to invite Ashley Cordova, our Chief Financial Officer, to close it out today. Thank you.
All right. Thank you, and thank you, Dr. Langer, Dr. Leal. Good afternoon, everyone, and thank you again for joining us today. I would like to start with a brief review of our commercial pathway to treating non-small cell lung cancer patients. The presentation of our LUNAR trial results earlier today marks an important step, next step in a round of engagements upcoming. We have already submitted these results for publication in a peer-reviewed journal, and our regulatory teams are preparing both the PMA and CE Mark applications for submission later this year. As a reminder, the FDA's review timeline for PMA submissions is 180 days, but that clock is paused for any correspondence between Novocure and the agency. Once we have gained regulatory approval, our goal is to treat patients as soon as possible while our market access teams take the necessary steps to secure reimbursement.
We expect to be treating patients in the later stages of 2024, with commercial and national reimbursement to follow in the coming years. As a part of our clinical strategy, we strive to broaden our labels and expand the eligible patient populations in solid tumors where we have proven efficacy. We have already taken these steps in GBM with our ongoing TRIDENT trial and our upcoming launch of KEYNOTE D58 in collaboration with Merck. We now have the chance to follow a similar path in the torso. We've been very clear that we do not plan to be one and done in lung cancer. The LUNAR results build upon years of clinical development in thoracic oncology, beginning with our phase 2 EF-15 trial and our STELLAR trial in malignant pleural mesothelioma.
The results from these trials, together with the profound results of the LUNAR trial, provide a strong foundation for the continued expansion of our lung cancer development program, with the goal to treat patients in earlier lines of therapy and together with multiple standards of care. I am very excited to announce today that we have a number of new clinical trials in various stages of design, regulatory review, and launch preparation. These trials will enable us to build upon the efficacy shown in the LUNAR trial, with the goal of expanding the pool of patients who can benefit from Tumor Treating Fields. We are planning to launch three new trials in lung cancer, aptly named LUNAR-2, LUNAR-3, and LUNAR-4. LUNAR-2 will evaluate Tumor Treating Fields together with immune checkpoint inhibitors and chemotherapy in first-line metastatic disease.
LUNAR-3 will focus on patients with locally advanced disease, studying Tumor Treating Fields with immune checkpoint inhibitors following chemoradiation. LUNAR-4 will evaluate the potential of ICI retreatment in metastatic non-small cell lung, using Tumor Treating Fields together with an immune checkpoint inhibitor in patients treated with an ICI and chemotherapy in the first line. To these three new trials, we continue to enroll patients in our KEYNOTE-B36 trial, which is evaluating Tumor Treating Fields with pembrolizumab in the first line. These next series of trials represent an important pattern for Novocure as we pursue opportunities to expand the addressable market in solid tumors where we have proven efficacy. Lung, we have multiple phase 3s set to read out before year-end 2024. The data from these trials will inform similar opportunities to expand our clinical pipeline.
As a reminder, we expect to release data from our phase 3 INNOVATE-3 trial in recurrent ovarian cancer later this year, top-line data from our phase 3 METIS trial in brain metastases from non-small cell lung cancer in Q1 2024, and phase 3 data from our PANOVA-3 trial in unresectable, locally advanced pancreatic cancer in the second half of 2024. We expect these four foundational trials to drive Novocure into our next phase of growth as we look to further expand our development pipeline, launch numerous commercial franchises and new indications, and continue exploring opportunities to extend the lives of patients. Building on more than 20 years of research and a strong commercial business in GBM, and with the opportunity to treat tens of thousands of patients on the horizon, we have never been more excited for the future of this company.
I'd like to thank you all for joining us here today and welcome you to stop by and say hello to members of our executive team, as well as investor relations after this event. As we often do, I would like to close today's session with our mission. Together with our patients, we strive to extend survival in some of the most aggressive forms of cancer through the use of our innovative therapy, Tumor Treating Fields. LUNAR is the first randomized trial in more than seven years to show a significant extension in overall survival for patients with metastatic non-small cell lung cancer post-platinum. The results hold the potential to make a meaningful difference in the lives of patients who are eager for new, well-tolerated, effective treatments. We look forward to the opportunity to reach these patients and many more in lung cancer and beyond in the coming years.
Thank you.