Good day, welcome to the BMS ESMO IR event. Today's conference is being recorded. At this time, I would like to turn the conference over to Mr. Timothy Power, Vice President, Investor Relations. Please go ahead, sir.
Thanks, Justin. Good afternoon, everybody. Thanks for joining us today for our 2020 ESMO Investor Meeting. I did want to make sure that you're aware that we've posted slides to bms.com that you can use to follow along with today's discussion, and obviously we'll have time for Q&A afterwards. Joining me today for the presentation are Samit Hirawat, our Chief Medical Officer and Head of Global Drug Development, as well as Chris Boerner, our Chief Commercialization Officer. Giovanni Caforio, our Board Chair and Chief Executive Officer, as well as some other members of our oncology team are also here for the Q&A. Before we get going, I'll read our forward-looking statements. During today's call, we'll make statements about the company's future plans and prospects that constitute forward-looking statements.
Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the company's SEC filings. These forward-looking statements represent our estimates as of today and should not be relied upon as representing our estimates as of any future date. We specifically disclaim any obligation to update forward-looking statements, even if our estimates change. With that, I'll hand it over to Giovanni. Or I beg your pardon, to Samit.
Thank you, Tim, and it is a pleasure to be able to speak with you, especially right after a very important meeting that has just happened, not only for the company but also for the patients that we serve in terms of bringing new medicines for the treatment of very serious diseases. If you go to the next slide number four. Today and over the last couple of days, three important trials with the first-line data release were presented that have the potential to expand the use of OPDIVO in tumor types that we're adding on overall to the overall development of OPDIVO.
To start off, as you see on the left upper corner of the slide, we are pleased that our dual I/O option in first-line renal cell cancer continues to demonstrate durable survival after four years in CheckMate -214 study, with more than 50% of the patients alive after four years. In terms of a first-time data release, study 9ER can potentially provide an important new treatment option for patients with renal cell cancer, combining OPDIVO with CABOMETYX. As it relates to upper GI malignancies, earlier today, positive data were presented from study CheckMate -649, where we have the opportunity to be first in line in the first-line setting for gastroesophageal cancer, a tumor with a high unmet medical need. In CheckMate -577, OPDIVO showed a benefit in early-stage esophageal cancer, which is now the second tumor type where OPDIVO has demonstrated benefit in early-stage disease. Slide five, please.
Going into just a bit of detail for CheckMate-9ER. Here you can see the trial design where a combination of nivolumab and cabozantinib was compared to sunitinib as a treatment for patients with previously untreated advanced or metastatic renal cell cancer. nivolumab 240 milligrams was administered along with 40 milligrams of CABO, compared to 50 milligrams of SUTENT. Patients included in trial encompassed all risk groups, meaning those meeting favorable, intermediate, and high-risk criteria. While the primary endpoint was progression-free survival, our key secondary endpoint in this study was overall survival along with overall response rate and safety endpoints. You can go to slide six. You have most likely seen the presentation of the data day before yesterday when you saw these strong efficacy results.
As a reminder, this trial met its primary endpoint of progression-free survival at an interim analysis along with overall survival, which not only showed statistical significance but also clinically meaningful improvements. As can be seen from the Kaplan-Meier curves, a 49% decrease in the risk of progression is very strong. In addition, there's a clear survival benefit that is observed across all patient subgroups, including across risk status and levels of PD-L1 expression. In the next slide, as we look at safety by leveraging 30-milligram dose of cabozantinib, 9ER study delivered strong efficacy with a very encouraging tolerability profile. The discontinuation rate of 15% due to any grade treatment-related AE is lower than that of other TKI IO combos on the market today.
Taken together, we believe that based on the combined efficacy and safety, OPDIVO plus cabozantinib has a best-in-class profile relative to the other IO plus TKI therapies. Chris will talk more about the opportunity as we work towards bringing this regimen to patients in the future. We can go to the next slide. Moving to the upper GI malignancies, we wanted to highlight another couple of trials for which we recently announced the top-line data, and these two trials were just presented at the Presidential Symposia at ESMO. The first one is from large development plan for OPDIVO in the metastatic setting. Patients were eligible for enrollment in CheckMate -649 study shown here if they had been diagnosed with gastric, gastroesophageal junction, or esophageal adenocarcinoma and had not received prior treatment for their metastatic disease.
The disease had to be HER2 negative. While this is a three-arm study, the Nivo+Ipi arm data remains blinded until its final planned analysis, and these data are expected next year. Regarding the Nivo+chemo arm, dual primary endpoints were PFS and OS in PD-L1 CPS more than 5%, which represents about 60% of the population enrolled in the study. OS was tested hierarchically, first in CPS greater than 5%, then in CPS greater than 1%, and then in all randomized patients. On the next slide, you can see that CheckMate -649 met both its primary endpoints. Shown here are the data of overall survival, showing a 29% reduction in the risk of death in patients with CPS greater than 5% and a 20% reduction in all comers.
This is the first time a PD-1 inhibitor has demonstrated a survival benefit in patients with gastric cancer, offering a potential new standard of care in a space where other studies have not been successful. We believe this is an important development for addressing a high medical need for these patients and an opportunity for the company, which Chris will talk more about in a few moments. The next slide, the safety data in the presentation confirms that the OPDIVO chemo regimen tested in CheckMate -649 is tolerable and consistent with what we have seen with prior studies of OPDIVO. The following slide, switching gears to the early-stage setting. This is a slide that I shared with you back in June at our investor series. Let me remind you of what we believe. We believe that immuno-oncology can play an important role in early-stage disease.
From a patient perspective, this is an opportunity to medically intervene early and provide a potential for cure of the disease. We already know that checkpoint inhibitors work in adjuvant melanoma, where these checkpoint inhibitors are active and are benefiting patients with melanoma in the long term. This is likely because the immune system is more intact in patients with early-stage disease. We're now seeing phase III data supporting the potential for OPDIVO in early-stage disease across another tumor type that is beyond melanoma with CheckMate -577 in esophageal cancer. On slide 12, you see patients with esophageal or gastroesophageal junction cancers are in tremendous need of adjuvant options, as the unmet medical need in this disease is very high. Esophageal cancer is the seventh most common cancer and sixth leading cause of cancer-related deaths worldwide.
For certain patients who do not achieve a pathologic complete response following neoadjuvant chemoradiotherapy followed by surgery, the outcomes are particularly dismal. There is a frequent recurrence of disease for many of these patients, as most patients, maybe up to 70%-75%, have a tumor that fails to achieve a pathologic complete response. These patients will generally live less than one year without disease progression, with no established adjuvant option to turn to. That's as you can see on slide 13. In CheckMate 577, we designed the trial to address this particular patient population facing high risk of recurrence. This trial studied OPDIVO monotherapy versus placebo in patients with resected Stage II or III esophageal or gastroesophageal junction cancer who received chemoradiotherapy prior to their surgery.
Patients were stratified by PD-1 status and histology. That is non-expressers versus expressers, with a cut point of 1% for PD-1, and squamous cell or adenocarcinoma histologies. Primary endpoint for the study is Disease-Free Survival, with Overall Survival being the secondary endpoint. The Overall Survival endpoint has not yet been assessed, and BMS, as well as investigators, remain blinded to that data. On slide 14 are the data you saw at the congress. I'll spend a few moments to touch on a couple of important things. The trial met its primary endpoint of Disease-Free Survival in esophageal and gastroesophageal junction cancer as an interim analysis. It is important to note this is the first time a benefit has been demonstrated in this population, offering a potential option for these patients for the first time.
You can see the strength of the benefit overall and across all subgroups, most notably PD-L1 expression, tumor location, and histology. Successful outcome in this trial further reinforces our view about the potential for OPDIVO more broadly in early-stage disease settings. On slide 15, you see the safety profile. OPDIVO in CheckMate 577 was well-tolerated with an acceptable safety profile consistent with what we know and have seen before. Overall, based on the combined efficacy and tolerability profile of this treatment, we believe that treatment rates for peri-adjuvant treatment could grow over time as physicians and patients recognize the promise of survival with OPDIVO, like we've observed in adjuvant melanoma as well.
On slide 16, here is another slide we shared in June, which depicts our broad registration program now reflecting the additional trials which have read out. We are excited to see our adjuvant program starting to bear fruit, as well as utilize these important near-term opportunities in first-line renal cell and first-line gastric cancer to potentially offer OPDIVO to a broader range of patients. Beyond these opportunities, our lifecycle management program across various tumor types and stages of disease with both mono and combination approaches. Two of these opportunities in particular are in combinations with new mechanisms like relatlimab and bempeg, which I will discuss briefly on the next slide. The journey in immuno-oncology doesn't end with lifecycle management of OPDIVO and YERVOY. We have two next-generation IO mechanisms under late-stage development. Bempeg, our IL-2 partnered with Nektar, and relatlimab, our anti-LAG-3.
We are studying how bempeg can be combined with OPDIVO, first in melanoma, and then in several of the other indications that you can see on this slide. As it relates to relatlimab, we are now testing this medicine in a randomized phase II/III trial, looking at what added benefit relatlimab might demonstrate on top of OPDIVO. Both these agents have the opportunity to provide additional therapeutic options for patients through next generation immuno-oncology innovation. On the next slide, I just want to remind you of the mechanism of action that we are pursuing in immuno-oncology with our LAG-3 inhibitor, relatlimab. The hypothesis behind this agent is that LAG-3 expression is associated with T cell exhaustion, and that could be leading to a form of primary or possibly secondary resistance to PD-L1 blockade or PD-1 blockade.
Blocking LAG-3 expression using relatlimab could allow for T cell activation in instances where T cell exhaustion is causing that lack of response. In addition to providing us with potentially registrational data from the ongoing first-line setting melanoma, this trial will provide us with data to probably inform potential life cycle management plans for future development of relatlimab. In the next slide before I wrap up, I just wanted to summarize. We are excited about the data shared at ESMO and for the ability to build on our presence in first-line renal cell, as well as expanding on the IO opportunities in the upper GI tumors. OPDIVO and OPDIVO-based therapies continue to offer life-extending options for patients facing serious cancers with unmet need, and we look forward to additional readouts from our robust program that we saw earlier across both metastatic and early-stage settings.
We continue to invest in innovative next-generation mechanisms and await pivotal data from our late-stage IO pipeline with relatlimab and bempeg. I will now turn it over to Chris to take you through the commercial perspective. Thank you.
Thanks, Samit. Good afternoon. I want to pick up where Samit left off and talk a bit about how we think about the data presented at ESMO from a commercial standpoint and how it fits into the broader IO growth narrative for the company. Starting on slide 21, as we've discussed previously, we've built a very robust business in IO of just shy of $9 billion globally last year. This reflects over 400 global approvals in a dozen tumor types, in the majority of which BMS IO is now standard of care. This book of business provides a strong foundation for continued growth in 2021 and beyond. An important component of that growth was obviously the launch of first-line lung cancer in the U.S. earlier this summer. Those launches continue to proceed well. I'm happy to discuss that further in Q&A, as you like.
We also last week received a positive CHMP opinion for OPDIVO plus YERVOY, combined with two cycles of chemotherapy, and we look forward to launching that regimen in Europe in the coming months. At ESMO this year, we saw data across two other tumor types that will also be important contributors to near-term growth. Let me spend a few minutes providing a commercial perspective on these. I'll start with renal cell carcinoma on slide 22. RCC accounts for roughly 1/4 of OPDIVO sales in the U.S., with OPDIVO plus YERVOY garnering approximately 35% share in the first-line setting. As you can see on the left-hand side of this chart, the vast majority of this use is in patients with intermediate and poor performance status, which is our labeled indication.
We've maintained this very strong position in first-line renal in spite of significant competitive pressures here, in large part because of the impressive long-term benefit of dual IO therapy. This long-term benefit was reinforced with the four-year survival data presented over the weekend, which you see on the right-hand side of this slide, with over 50% of patients alive at 48 months and a relatively stable hazard ratio compared to the last data update at ASCO GU. Moving on to the next slide 23. It's into this context that we anticipate introducing the 9ER combination. Over the last number of months, we've had the chance to discuss with key customers the highlights of the data Samit just went through and which were shared at this conference.
The consistent feedback we hear is that the OPDIVO plus CABO regimen compares favorably to existing IO TKI options, as evidenced by the impressive OS and PFS benefit that compares very well against existing therapies and a very manageable safety profile. Given this profile, we see multiple opportunities to build upon our existing position in this market by displacing existing single agent TKI use, which you'll note from the previous slide, still accounts for approximately 20% of current frontline use. We also see the opportunity to extend the benefits of OPDIVO-based therapy into the favorable risk patients with this regimen, which as I mentioned, is currently off-label for us. Finally, we see the opportunity to compete effectively in patients receiving currently available IO plus TKI options.
Importantly, once approved, we'll be the only company to offer multiple IO-based options to renal cell cancer patients, both dual IO and what we believe is the most compelling IO plus TKI option. Moving on to gastric cancer on slide 24. We are very excited with the opportunity to bring IO therapy to first-line gastric patients. As noted on this slide, gastric cancers, including gastroesophageal junction cancer and esophageal cancer, are among the top 10 deadliest cancers worldwide. They are also cancers where we have seen limited advancements in over a decade, resulting in a substantial need for therapies that improve survival in the metastatic setting, and as we'll discuss on the next slide, prevent recurrence in locally advanced disease.
With the CheckMate -649 data Samit just reviewed, we are very excited with the potential to be the first and only IO regimen demonstrating a superior survival benefit versus chemotherapy in non-HER2-positive disease across upper GI tumors. From a commercial standpoint, I'd highlight a few things about the opportunity here. The early feedback from physicians with whom we've shared these data has been very promising. Specifically, they note the compelling survival benefit that offers the potential to improve on current standard double chemotherapy in these upper GI tumors. The fact that clinical benefit was shown across PD-L1 expression levels is also viewed as important, as is the fact that these benefits were accompanied by a generally manageable safety profile.
Second, I would also note that while this is a new tumor for IO, this is a customer set we know well and which has experience with IO and OPDIVO-based regimens in other tumors. Bottom line, we're very excited about the opportunity we have in this data. Moving on to slide 25. The 577 data give us the opportunity to move IO therapy into early stage esophageal cancer. As we have discussed within the context of our adjuvant melanoma experience, we know that when we are able to introduce effective IO therapies in early stage disease, we have the opportunity to not only treat the set of patients being treated with existing therapies, but also expand the pool of patients available for treatment. In fact, in melanoma, we saw a greater than twofold increase in treatment rates.
In early stage esophageal cancer, as Samit noted, there is a significant unmet need for patients. Only about 45% of stage two, three patients today receive neoadjuvant chemotherapy plus radiotherapy, and the treatment rate post-CRT resection is extremely low. Moreover, among those who undergo surgery with CRT, the majority do not receive a complete response, portending a high risk of recurrence and progression to metastatic disease. Finally, while neoadjuvant and perioperative chemotherapy is used in a number of patients, there are still no systemic adjuvant therapies available for patients, and outcomes remain poor. Based on the 577 data presented at ESMO, we believe we have the opportunity to drive adoption of adjuvant OPDIVO across upper GI tumors post-CRT and surgery. As Samit highlighted, the study demonstrated a highly significant and meaningful increase in Disease-Free Survival.
That benefit was seen across subgroups. Importantly, given this is early-stage disease, the benefit was accompanied by a well-tolerated safety profile. Obviously, it's still early days. We'll continue to engage customers now that the full data set has been presented. We think OPDIVO has an important role to play for stage two, three patients with esophageal and gastroesophageal junction cancers. Next slide, please. Let me close here on slide 26. As we've discussed previously, we have a strong base of business today across multiple tumors globally. We are happy with the early experience we're having in first-line lung cancer with our U.S. launches and look forward to the launch of the 9LA regimen in Europe in the coming months. We're very pleased with last week's positive CHMP opinion supporting that launch.
At this conference, we've heard about data in two additional tumors that will be near to medium-term catalysts for IO growth. In renal cell carcinoma, the updated CheckMate -214 data for OPDIVO plus YERVOY continue to emphasize the longer-term durable survival benefit seen with dual IO therapy. Data from CheckMate -9ER allow us to build upon this leadership position by providing what we believe is the best-in-class IO TKI option for patients. We see meaningful opportunities where we can grow our business with this regimen. CheckMate -649 and CheckMate -577 provide us the opportunity to establish IO and OPDIVO specifically as an important treatment option for patients with upper GI tumors in both frontline metastatic setting as well as early stage disease.
Collectively, the data presented here are part of a robust set of life cycle options for our existing IO agents, as well as the potential we have with next generation assets, including relatlimab and ZINPEX. With that, I'll turn it back over to Tim to moderate the Q&A. Great.
Thanks very much, Chris. As a reminder, as well as Chris and Samit, we have Giovanni Caforio, our Board Chair and Chief Executive Officer, on the line for Q&A, as well as some of the folks from our oncology team as well. With that, Justin, if you don't mind, can we go to the first question, please?
Thank you. Our first question will come from Chris Schott with JP Morgan.
Great. Thanks so much for the questions, and congrats on the data here. I just have two. Maybe first on adjuvant esophageal, can you just talk about the penetration rates you've seen with OPDIVO and combos in adjuvant melanoma? Should we think about that as a decent analogy when we think about what you can achieve in this esophageal setting, and if there's any similarities or differences that you'd highlight there? Maybe just also get an update in terms of where you stand in terms of the frontline non-small cell cancer launch in the U.S. type of share that you're seeing. I think with the 2Q results, you talked about some very encouraging trends. Can we maybe just get an update of how that's progressed over the last, I guess, month and a half or so since that last update? Thanks so much.
Sure. Thanks for the question, Chris. As you know, the penetration we've seen in adjuvant melanoma is roughly around 40%. That was a tumor where treatment rates were very low when we launched IO into that setting. We've grown those treatment rates to upwards of 80% today. I think there are some fundamental differences as you look into esophageal cancer. This is a setting in which you've seen very little systemic use of any agent for patients in the adjuvant setting. This is an area where it's not really one disease. It's actually multiple diseases. As you may know, 577 is a study that covered esophageal adenocarcinoma and squamous cancers, as well as gastroesophageal junction cancers. I don't think you can really compare in terms of the underlying dynamics of melanoma to what we see in this particular space.
What I will say is comparable, though, is the level of benefit that we're seeing with IO therapies. We're very excited with the data that we've seen with 577. Remember, this has the opportunity to be the first IO to market in the early stage esophageal setting. The data here are very compelling, a doubling of DFS with a manageable safety profile. Based on that, we think we have the opportunity to significantly improve on the outcomes for patients, which, as Samit noted, the majority of patients, in fact, about three-quarter of patients who undergo CRT and resection do not actually get a pathological CR, and that portends very bad outcomes for those patients. We're excited about the opportunity that we have here.
I would just be a little bit reluctant to do a simplicity look at what our penetration rates were in melanoma and apply it in here. These are different diseases. With respect to first-line non-small cell. Sorry. Let me make a few comments, and then we have the head of our U.S. business, Adam Lenkowsky, on, and he can jump on as necessary. What I would say is we continue to be very happy with the performance of the launch. As I mentioned in the second quarter call, we're seeing penetration rates in the mid to upper single digits. We'll obviously give you an update on that as we get into the third quarter call. We continue to see very good execution here. We've reached a high percentage of the high-prescribing physicians in this space.
This is, as you know, a space where the community physicians are very important, and so we've been targeting those physicians who have experience in the community setting with OPDIVO and YERVOY and other tumors, and again, that's an area where we've seen very good engagement. We're particularly excited because, as we noted on the second quarter call, we are not seeing physicians pigeonhole the use of OPDIVO and YERVOY in lung cancer into a specific patient type. We're actually seeing use really across a broad swath of patients. The majority of the use is in the PD-L1 to 49% segment. We are seeing some use above 50% PD-L1 expression. We're starting to see a pickup in the PD-L1 negatives and non-expressors. That's the regimen that is covered, or that's the space that's covered by the 9LA regimen. Overall, very happy with what we're seeing in first-line lung.
Adam, anything to add there?
I think you said it well. We're very encouraged by the uptake. It's still early. We're approximately three months post-approval. We knew entering the market this was going to be an entrenched market with KEYTRUDA and KEYTRUDA plus ALIMTA. As Chris mentioned, our share in just over three months is now in the mid to high single digits, and we're seeing continued growth, and we're seeing use across all PD-L1 expression, as well as in squamous and in non-squamous. What we're hearing back from our physicians is our profile for both 227 and for 9LA, the profile is differentiated. The durability, the three-year landmark survival, and the chemo-free messages are all resonating. We've shown that we're increasing awareness, particularly in 9LA, because 9LA launched after CheckMate -227, and we're seeing uptake now with that regimen largely in the negative.
Our team's done a very nice job with remote engagement. We've been almost exclusively virtually engaging our customers, and we've penetrated our highest value customers over 60%.
We're focusing on our OPDIVO prescribers as early adopters. We've been ahead of our competition in YERVOY. Lastly, I'll mention, you probably have seen, we launched a national direct-to-consumer campaign last week to help educate patients and hopefully drive patients in to ask and have a dialogue with their physicians around OPDIVO and YERVOY and the durability and chemo-free option for long-term survival.
Thanks very much, Adam. Justin, can we go to the next question, please?
Absolutely. Our next question comes from Seamus Fernandez with Guggenheim.
Thanks so much for the question. Just wanted to get a quick sense. When we look at the tolerability of the 9ER regimen. Frankly, this looks better tolerated than any other TKI regimen. It looks better tolerated than OPDIVO plus YERVOY. Why wouldn't this be your leading option, particularly given the robust PFS? Obviously, that was the message from the discussion. Separately, just wanted to get a better sense in the gastric cancer setting. Would you guys help us understand where the most likely first-line gastric cancer opportunity you believe is? Is this really an area globally where you expect use in gastric cancer plus chemo to be in the 5% plus patient population, 1% plus PD-L1 positive, or is it your expectation that the benefit is actually across the entire patient population?
I know it was statistically valid in the overall population, but just wondering how you expect treatment to evolve globally given the results presented over the weekend. Thanks.
Sure. Thanks, Seamus. I'll take that. Then Samit, you can obviously add in as you need to. With respect to first-line renal cell, I think that you characterize the way we see 214 and 9ER pretty well. I think that, in fact, the discussant summarized it as well. We think we have the best-in-class IO TKI regimen with OPDIVO plus cabozantinib. I think the data that we've seen with 214, both from an efficacy and safety standpoint, continues to impress with the long-term durability of that. In terms of how this ultimately will be used, we actually think that there's an analog to the way that physicians have begun to think about these regimens in first-line with what we saw in second-line.
When we launched IO in second-line, what we saw is physicians were choosing to use TKIs for those more aggressive patients where you needed to get an immediate response. For those patients where you could allow IO time to work, they would opt for IO therapy. That's begun to be the approach that physicians are using as they think about CheckMate -214 and existing IO TKI options. We're very happy now to be the only company to have multiple IO approaches to offer in this space. We think we've got a best-in-class IO TKI with OPDIVO CABO , not only from an efficacy standpoint, but also a very good safety profile. Again, as the discussant mentioned yesterday, a good opportunity for those patients who need a very quick response.
For those patients where you're looking for a long-term benefit, 214 provides an option there. Happy to be able to have both of these regimens available for renal cell patients, and I think that's roughly how we're going to see that segment out. With respect to how we think about gastric and first-line, I think that the 649 data have clearly demonstrated an improvement across all patient segments. The data is particularly strong, as you noted, in CPS greater than 5%. What's on label is ultimately going to be a regulatory discussion. We'll have to see how those discussions play out both in the U.S. and ex-U.S.
What I would say is that given this is a space where we've not seen much in the way of innovation in over a decade, given the significant unmet need here, I think you're likely to see physician interest, certainly in the U.S., to be in a very broad patient population. As you get outside of the U.S., given HTA dynamics, we may see a different set of dynamics play out there. We're going to have to wait and see how the regulatory discussions go, and it certainly arguably that the benefit here is across the entire population.
Hey, Justin, can we go to the next one, please?
Thank you. Our next question comes from Steve Scala with Cowen.
A few questions. First, Asian markets, as you've noted, are key to the GI indications. What are the timelines for filing in Japan and China, and can you remind us of the Bristol Myers Squibb Asian footprint in terms of sales force? Secondly, Bristol has a TIGIT, but it gets little attention. Now that a second company has shown positive results, is your view changing? Thirdly, if you will allow me, Bristol recently said that the liso-cel plants had not been inspected yet. Can you tell us if the dates have been set to inspect each plant? Thank you.
Samit, do you want to start?
Sure. Maybe we can start with, well, in the order that you asked. First of all, in the Asian market, the filing timeline around the data for gastrointestinal tumors that we're just studying the upper GI, because obviously very important data, and we see the data applicable from these global studies, both in the adjuvant setting as well as in the first-line setting. We have a global registration strategy already that we work through, and since the trials have been global from across the globe, we will be discussing these. We cannot today tell you exactly the timeline, because there are lots of pre-submission meetings that we have to carry out with health authorities. As the timelines become more finalized, we will certainly communicate those. We are working towards those aspects of filing.
From a TIGIT perspective, certainly we are looking, obviously, at the data that was presented recently at ESMO from other companies. We have our own TIGIT, as we have said before, which is in phase I right now. We are continuing to evaluate that. It's not that we change our strategy. We just have to wait for the phase I data to read out from both the safety perspective, dose perspective, and any hint of activity perspective, and then we will be able to share further what our development plan will be for TIGIT. The third question you asked was about liso-cel, and as we have recently communicated, both myself as well as Giovanni and others, we have now spoken publicly that we continue to work with the FDA in terms of assessing when the inspections will be. These plants have not yet been inspected.
Just a reminder, we do have a Breakthrough Therapy designation. A reminder that we have a PDUFA date in November. As soon as the FDA will inform us, we'll certainly take that into account. Right now, we don't have a date for inspection of the plants, and they have not been inspected yet. Thank you.
Just very quickly on the presence in Asian markets, we have a presence in all of the key Asian markets. Certainly, as you know, gastric is an important potential opportunity in those markets.
Great. Okay. Thanks, Justin. Can we go to the next one, please?
Our next question comes from Geoff Meacham with Bank of America.
Hey, guys. Thanks so much for the question, and congrats on all the updates at ESMO. For Chris, on 9ER, I just want to understand the commercial positioning of Nivo + Ipi versus Nivo + CABO. Just what are the puts and takes for IO versus IO TKI share in renal? For Samit, data for 649 was strong, but looking at the tail of the curve, it's not really close to what you see in other IO-sensitive tumors in terms of long-term OS benefit. Do you think gastric is just a difficult indication that's less immunogenic or IO doublets or triplets needed, in your view, to improve OS further? Thank you.
Maybe I'll start, and then I'll turn it over to Samit. With respect to the puts and takes for 9ER, as I said earlier, I think that as we look at where 214 and 9ER will be positioned, I think you're likely to continue to see physicians look to IO TKI options for those patients who need a more immediate response or have a more aggressive disease. They'll opt for 214 potentially for those patients with less aggressive disease where they have more time for IO therapy to work. The other thing I would note is that 9ER, because it included patients across performance status, gives us the opportunity to promote in the favorable patient population, which, as I mentioned in the presentation, we don't have the ability to do in 214.
That's something that is somewhat unique to 9ER and is an important opportunity for us. With that, I'll maybe turn it over to Samit.
Thank you, Chris. For 649, we agree. Look, there are two things to note over here. One, as you very well pointed out, very difficult and it's a very challenging tumor type to treat. The fact that we've been able to isolate the effects and making a difference in the overall outcome, both from a progression-free survival and overall survival benefit, that is an addition to these patients and their outcomes. We need to do more, both from longer-term follow-up to see what the tail will ultimately evolve into. We still need to build that data further up. You're absolutely right. I think new therapies will need to investigate if they can add more from that perspective to elevate the tails of the curve further than what we currently see.
More biomarker work needs to be done, isolate the effects beyond the CPS 1, five, and oncomer. What else can we do to really make a difference to the lives of these patients? It is a challenging tumor. We do see that the Asian patients in general, like in Japan, they do better because they have more surveillance programs, smaller tumor types that are treated much earlier, as you also heard during the ESMO presentation. Maybe some of those things will need to be taken into account as well in the future as we continue to build towards improving overall outcomes for our gastric and upper GI tumors.
Thanks so much, Justin. Can we go to the next question, please?
Thank you. Our next question will come from Tim Anderson with Wolfe Research.
Thank you. Discussants of the 577 adjuvant data criticized the use of DFS as a primary endpoint. In early-stage cancer, I've been under the impression that that's an appropriate, reasonably well-accepted measurement, and I'm hoping you can comment on whether you think that was an unfounded criticism. Related to that, in Europe at least, could it be that you don't secure widespread reimbursement until you have OS results in hand, especially because there was no benefit seen in patient-reported outcomes? When do you think you might have OS results?
I'll start and I'll pass it on to Chris. You're absolutely right. We do believe that if you look at any tumor type, RFS, DFS, whether it be melanoma, breast cancer, colorectal cancer, and many of the other tumor types, the approval of drugs have been based on disease-free survival or relapse-free survival endpoints.
These are settings that there is a lot of guidelines that have been provided by regulators. We don't believe that from a regulatory point of view, there is any question about use of DFS as a primary endpoint and approval to the endpoint. As you know, overall survival is a secondary endpoint, and patients are being followed for that. It remains blinded because we don't have enough events yet in the study to really make a good analytical output in terms of the results that will be meaningful. We will continue to work with the DMC, or data monitoring committee, to understand that when we will have the data. At that time, we'll be able to share that with the regulatory agencies and beyond that. From a reimbursement perspective, how difficult it will be, maybe, Chris, you want to comment on that?
Sure. The only thing I would just add on the DFS point is that not only is there clear precedent, there's very strong interest on the part of customers around the benefit that we've seen on DFS. I think uniformly across geography, customers view that as a meaningful improvement. As you note, in some markets, there may be a requirement for overall survival, though I would say that given the timing of HTA assessments in European markets, we may actually have OS data by then. Obviously, that's going to be dependent upon the data. As you well know, these typically are sequenced, and so we may have some OS data as we get into European markets given the timing. The only other thing I would add is that patient-reported outcomes really will not impact reimbursement in a meaningful way.
Chris, thank you. Hey, Justin, can we move to the next question, please?
Absolutely. That will come from Terence Flynn with Goldman Sachs.
Hi. Thanks for hosting the call, and thanks for taking the question. Was just wondering, as you think about the CheckMate-816 study in lung that's going to read out later this year, just wondering if you can remind us what magnitude of improvement you're hoping to show here, and if you'd be able to file for approval on a pCR endpoint, or if you'd also have to wait for EFS data in that setting. Thank you.
I can start off over there. Maybe the second question first. As we have discussed earlier, from a pCR as an endpoint perspective, certainly has been used in other diseases, but there is no precedence yet set for non-small cell lung cancer as a pCR as an endpoint. Something that we will need to discuss with the regulatory agencies, and it will obviously probably depend on the magnitude of the data once the DMC shares that with us. If the DMC will share with us the data, then we can certainly engage the regulatory authorities in those discussions. That is yet to be seen. We are waiting to hear from the DMC once the data are available and ready for analysis.
In terms of the magnitude that we're looking for, these are competitors, depends on what the placebo arm will show, of course, what the treatment arm will show. I can't give you the magnitude that we're looking for to define success. There were statistical assumptions that we've placed in the protocol, when the DMC reveals data, we'll be able to get better guidance.
Okay, great. Justin, can we go to the next one, please?
Our next question will come from Dane Leone with Raymond James.
Thank you for taking the questions, congratulations on all the updates across your programs as of this year. A lot of progress. Great for Nivo. The question I'll limit myself to is just on CheckMate -649. As you're anticipating the regulatory discussions on this study for approval, how do you think the narrative will go around the point of maybe having an enriched patient population for the CPS greater than five? That did come up in the discussion session today. How are you thinking about your approach to how you would want the indication to be written on the updated label and think about all patients versus having that segmented scoring? Thank you.
Thank you for the question. From the study perspective, it is an all-comers study. We did not enrich any of the patient populations. Of course, when we look at the data now, we see that approximately 60% of the patients did fall in the category of about 5%, and that was certainly one of the primary endpoints. Then, of course, there was a hierarchical testing, as you also heard. We do believe that the overall benefit has been observed, not only in patients with CPS greater than five, but also overall survival benefit has also been shown in all comer populations. Those are the discussions we'll have to have with the regulatory agencies. Overall, we'll see what the regulatory agencies ultimately will come to a conclusion with, but our interpretation of the data is the benefit is seen in all comers.
When we look at overall response rate, overall survival, all patients are benefiting. That's what our position will be going into the discussions with regulatory agencies, both for the FDA and the European side.
Okay, great. Could we go to the next one, please, Justin?
Our next question comes from Matt Phipps with William Blair.
Good afternoon. Thanks for having me. Definitely have no updates. Just one question. You guys interestingly bring up relatlimab quite a bit in today's presentation, even though we haven't really talked about it much since the initial look at a refractory phase III melanoma population. My question is really not so much with the melanoma trial, but how much of the success of that trial is going to be required to move the fixed-dose combination of OPDIVO and relatlimab forward into additional development? I believe that's kind of the lifecycle management program you mentioned as well.
Thank you for the question. Relatlimab certainly is an important immune checkpoint inhibitor that is being investigated. As I said earlier, melanoma is the venue that we are first investigating. Certainly, the fixed-dose combination that you have talked about is important. Now as we look at the additional indications, as we look at the data emergence, and we look at the overall development plan going forward, it will play an important role, certainly from a commercial perspective. Chris or Adam might want to comment on that. From a development perspective, defining those pathways of how to combine the two drugs, give them together at the doses that we will be able to take forward, not in one indication, but a multitude of indications, because the applicability could be quite wide. We have to certainly test that out.
We are looking forward to readout in the early part of next year for the first study and deriving the life cycle management plan going forward. I don't know, Chris, if you or Adam want to comment on commercial aspects.
I think you've covered it mainly. I think there's obviously, we've had tremendous success with our existing therapies in melanoma. The bar is high, but there's always room for potential improvement, not only in efficacy but continue to improve on safety. We'll have to wait and see how the data pan out, but we're excited about the possibility of adding relatlimab in this setting.
Thanks, Chris, and thanks Matt for the question. Justin, I think we've got time for one last question.
Certainly. That question will come from Navin Jacob with UBS.
Hi, this is John Lim on for Navin Jacob. Thank you for taking our question and congratulations on the data. Looking at the CheckMate -649 data, we noticed that the overall survival hazard ratio confidence interval for gastric was a bit tighter and didn't cross one versus those intervals for GEJ or EAC primary tumors. How should we think about this, and what could this mean? Do we know very well where the primary is, and is there any confusion?
I had a muffled voice. I'm sorry. Can you repeat the question, Tim or Chris? Anybody.
Yes. We were looking at CheckMate -649, and we noticed that the hazard ratio confidence intervals for overall survival for gastric primary was a narrower interval that doesn't cross one. For GEJC or EAC primary, those confidence intervals are a bit wider, and we were just wondering what we should make of this.
Oh, sure. Absolutely. In the overall population, if we think about it, we've got an overall benefit. When we start to cut the data further and further, if you look at the forest plot, you've seen that in the gastric cancer population, we've got a sample size of 667. You get to see a little bit more power to be able to do that analysis and get a hazard ratio of 0.66. For doing the GE junction as well as the esophageal adenocarcinoma, you've got 170 patients and 118 patients respectively. That overall hazard ratio still remains beneficial at 0.84 and 0.78 respectively. If you look at the overall median, it's 14.2 months for GE junction cancer, for example, and 11.2 months.
Again, one has to really keep in mind when we start to drill down in the data and the sample size gets smaller and smaller, it's hard to keep the intervals as tight as you would see with a larger population. I think the more important point is when you look at all the endpoints in this study, when you look at PFS, when you look at OS, when you look at overall response or duration response, are you able to keep the trends in the right place beyond the primary and secondary endpoints? That's I think going to be very important, and that's what it depicts in general. That's our take from the data.
Great. Well, thanks everyone, and thanks everybody for your time today.
I think today was a great meeting for the company, for our patients, and if you've got follow-up questions, you know where to find us afterwards. Thanks again.
Thank you.
Thank you.
Bye.
Thanks everyone.
That does conclude today's conference. We do thank you for your participation. Have a wonderful day.