Greetings, welcome to the Corbus Pharmaceuticals 2026 ASCO Data Update conference call and webcast. At this time, all participants are in listen-only mode. A question-and-answer session will follow the formal presentation. You may be placed in the question queue at any time by pressing star one on your telephone keypad. As a reminder, this conference is being recorded. If anyone should require operator assistance, please press star zero. It's now my pleasure to turn the call over to Dan Ferry, Managing Director with LifeSci Advisors. Please go ahead, sir.
Thank you, operator. Good morning, everyone, and welcome to the Corbus Pharmaceuticals 2026 ASCO Data Update call. As a reminder, during this call, we will be making forward-looking statements, which are subject to various risks and uncertainties that could cause our actual results to differ materially from these statements. Any such statements should be considered in conjunction with cautionary statements in our press releases and risk factors discussed in our filings with the SEC, including our quarterly reports on Form 10-K, excuse me, reports on Form 10-Q, and annual report on Form 10-K, and cautionary statements made during this call. We assume no obligation to update any of these forward-looking statements or information. It's now my pleasure to turn the call over to your host, Dr. Yuval Cohen, CEO of Corbus.
Thank you, Dan, good morning, everyone, for joining us. It's my pleasure to provide a detailed overview of the data we will be presenting at ASCO in just a few days' time. This data represents an April 1st data cut. I'm joined today by Dr. Glenn Hanna, Director of the Center for Cancer Therapeutic Innovation at Dana-Farber Cancer Institute. Dr. Hanna completed his fellowship training in hematology and medical oncology at Dana-Farber Cancer Institute in 2016. Prior to this, he earned a medical degree from Georgetown University School of Medicine in 2010, where he graduated summa cum laude and was a recipient of the Colbert Medal for Academic Excellence. He's the director of the Center for Cancer Therapeutic Innovation, CCTI, the early drug development program at DFCI. His clinical and translational research efforts focus on precision medicine approaches to treat head and neck cancer.
You may remember Dr. Hanna from our KOL ESMO event that we did last November. Following the presentation of the data, I'll have a brief Q&A with Dr. Hanna, and then we will open it to questions from our audience. Just a reminder, we have three events coming up at ASCO. Starting on Friday, our cervical data will be presented as an oral presentation on Friday afternoon. On Saturday afternoon, our head and neck data will be part of the poster session for head and neck. Lastly, on Monday morning, we will have our KOL event joined by the three KOLs, who also were kind enough to join us in Berlin last November at ESMO, Dr. Hanna, Dr. Perez, and Dr. Rosenberg. With that, let me jump straight into the data. I'll move at a pretty fast clip.
The press release has been out now for about an hour. This deck can be found on our corporate website, and let me just go through the highlights quickly. In slide six, a reminder that everything we see data-wise around this ADC derives from the structure of this ADC. This is a very, very stable Nectin-4 targeting MMAE-armed ADC that has the ability to hang on to its payload for much longer. It also means that it can be dosed far less frequently. What we have seen both at ESMO and now at ASCO as well, is that we continue to see levels of MMAE-related toxicology or toxicity that are certainly below everything that we've seen with other such ADCs. The data at ESMO was on both our dose escalation and dose expansion.
The ASCO data focuses now on two specific tumor types, head and neck and cervical, at the two relevant doses, one of which is now moving forward. We've seen it comprises of the patients you saw at ESMO, as well as some additional patients that were not yet scanned at the time of the ESMO presentation. Our safety database has nearly doubled to 317 patients. This includes all the patients that we have dosed at all the doses, all the tumor types, including tumor types that we have yet to present. Our head and neck population has gone from about 60 patients at ESMO to about 75 patients at ASCO, and cervical has gone from about 50 patients or so at ESMO to 72 patients at ASCO. I'll start with the safety.
On the safety side, what's been encouraging is that overall, the picture is very similar to what we saw at ESMO, despite the fact that we've doubled the number of patients in the safety population. We continue to see relatively few grade 3s and very few grade 4s. This entire safety population has a sum total of just 3 grade 4 events and has been thankfully no grade 5 events. We continue to be best in class for peripheral neuropathy, all of it grade 1 or 2, none of it grade 3 or above, and it continues to be well below 10%. We also have a markedly better skin toxicity than other such ADCs, especially PADCEV, with skin tox being mostly grade 1 and 2, and the sum total of a single grade 3 skin tox with no grade 4 or above.
Ocular continues to be a feature of this ADC as we've seen with this class of ADCs. No big changes there. Again, the vast majority are grades 1 and 2. We have grade 3 hovering at just above 10%, and there was just a single reversible grade 4, which is a feature of this ocular tox that tends to be reversible. Most importantly, for the ocular toxicity and in general for the overall toxicity, our rates of discontinuations continue to be very low and in fact have improved since the ESMO data set. If I could turn your attention to the next slide. We have, again, peripheral neuropathy well below 10%, none of it grade 3 or above. Skin toxicity, again, markedly different than what we would see, for example, with an ADC such as PADCEV.
Last but not least, the ocular tox, as we're specifically looking at reductions and interruptions for ocular tox. They are part of the way in which the physicians manage these toxicities, and the discontinuation rate specific to eye tox is below 2% in them. Let's jump straight into the data, starting with oropharyngeal head and neck cancer. A very simple explanation of what oropharyngeal head and neck cancer is, or colloquially throat cancer, it is basically the back of your teeth to the top of your throat, including the base of your tongue. What's interesting about this cancer type is that it is on the rise. If we look at the prevalence of this cancer, it is driven by HPV infections, and those are rising, frankly, at an alarming rate from about 11% 30 years ago to more than one in two patients for head and neck.
We can also look at the incidence that has also risen at an alarming rate while the incidence of HPV negative head and neck cancer, and a reminder, that is the head and neck cancer that is driven primarily in much older men with a history of smoking and/or excessive drinking. That patient population is not increasing. In fact, it is beginning to shrink as that generation dies off sadly and is not replaced by younger drinkers or smokers. What would be the hypothesis for a Nectin-4 MMAE ADC working in oropharyngeal cancer? There are three elements to this.
One, it is a cancer that is driven by the HPV virus, and we have an example of a cancer driven by the HPV virus in which Nectin-4 MMAE works very well, and that is cervical cancer, which is something along the lines of 98% HPV positive, whereas oropharyngeal is not that far behind it. About 80%-90% of those patients are HPV positive. The second fact to consider is it is a cancer type that's known to be associated with high levels of Nectin-4. Head and neck cancer, and specifically this type of head and neck cancer, is one of the enrichiest cancers in Nectin-4, again, fitting into the same pattern as cervical cancer, another Nectin-4-rich cancer type. Last but not least, we actually have a precedent here of a Nectin-4 targeting MMAE ADC in the form of PADCEV.
Specifically, as you'll see in a few slides from now, the front-line therapy of PADCEV plus pembrolizumab in head and neck, and the breakdown that slides are provided between their HPV positive population and their HPV negative population. If we look at our division in our head and neck cancer and a reminder that this was one of the seminal questions that were left unanswered at our ESMO presentation, it was how do we split between HPV positive or oropharyngeal and HPV negative or the non-oropharyngeal head and neck? What you'll see is that our breakdown in our U.S. and European sites fits nicely into the 50/50 breakdown, with roughly half the patients being HPV positive or oropharyngeal and half of them being non-oropharyngeal.
This is another way of looking at our own data, as you can see, unsurprisingly, our oropharyngeal patients are overwhelmingly HPV positive, as you would expect. The mirror image of that are our non-oropharyngeal patients who are overwhelmingly HPV negative, as you would expect as well, again, from a population that's derived from the U.S. and Europe. A question, again, going back to ESMO was where would the efficacy lie in terms of bias or preference between these two very different types of subpopulations? As you can see, the answer is markedly clear cut in oropharyngeal patients that represented 41 of our patients. We have a pretty marked response. Their chances of responding were very high, with a confirmed objective response rate for the higher dose of nearly 43%.
The exact mirror image of that in the non-oropharyngeal patients, the HPV negative patients, where the response was very modest. What's particularly striking about this slide is that it is the mirror image of what you would get with an EGFR bispecific. Those, a reminder, have a strong bias in favor of the HPV negative patients, the non-oropharyngeal patients. In fact, two of the three EGFR bispecifics currently being explored explicitly exclude HPV positive patients. Another question we were asked at ESMO was durability. The ESMO data set was too immature to provide durability. Now, for the first time, we can look at ongoing durability, and what we see mirrors the objective response rates. We have a durability in the 3.6 milligrams that is already exceeding six months with a PFS that is catching up to it.
In the non-oropharyngeal, of course, this is a patient population that would not be sensible for a drug like this. Again, a reminder, this is also a patient population where we would not expect Nectin-4 to be greatly expressed. As a summary, a question we've been asked often in the last several months, which of the two doses would be more sensible to move forward? The answer is the 3.6 milligram per kilo dose dosed at Q3 weekly. As you can see in the summary, the confirmed overall response rate was nearly 43%, a DCR of nearly 86%, a DOR of 6.3 months, a PFS of 5.6 months. Both of those are ongoing. Lastly, we do not exclude patients or do not mandate that patients be HPV positive, only that they be oropharyngeal patients.
In fact, eight out of our nine patients were also HPV positive, as you would expect from the demographics of this disease. Another key question that we were asked at ESMO is, how would this fit in the landscape in second-line monotherapy compared to petosemtamab, previously at Merus, now at Genmab? Luckily, we can actually look at that data from the, at the time, Merus data set. The Merus data set, a reminder, showed a very nice response in the HPV negative, but their HPV positive response was modest, with only 15 out of two patients responding. They looked at oropharyngeal patients who are also HPV positive, so there's a double restriction there. Luckily, we can actually look at the same thing in our data set.
When we look at our oropharyngeal who are confirmed to be HPV positive, we get a confirmed response rate of eight out of 16. As I've mentioned, our strong preference moving forward would be to use the anatomical definition of oropharyngeal and enroll patients regardless of their HPV status. Our durability, whether it's median DOR or PFS, already seems to be matching or exceeding those seen in the Merus data sets, despite the fact that they did not break that down into HPV positive or negative. As you can see, our tolerability also seems to be superior to theirs. This is our path forward. TEMPO-1 is a single controlled registrational study that will launch this summer. It starts with 250 patients, whether on half on monotherapy of CRB-701 and half on physician's choice.
It has an adaptive feature and the primary endpoint under accelerated approval, the ORR, with a full approval based on OS. As we've mentioned a few weeks or months ago, we have alignment with this with the FDA. We will provide more data on this both at ASCO and a little bit after that as well. An intriguing view into what we could see in our frontline study. We are currently dosing patients in frontline head and neck using CRB-701 plus Pembro or KEYTRUDA. We will have our data, we hope, at the beginning of next year. In the meantime, there is a precedent, an intriguing precedent to that, and that's looking at PADCEV. This was the Pfizer now data at ESMO last year. What we saw with PADCEV plus Pembro in frontline was an overall response rate of 39%.
That comprised of both HPV positive or negative, or oropharyngeal, non-oropharyngeal. TIVDAK showcased a very similar bias towards the HPV positive/oropharyngeal that we do in second-line monotherapy with a confirmed ORR of 82% for HPV positive and a confirmed ORR of far more modest 23% in the HPV negative. To just juxtapose it, again, this theme that this looks very much like the mirror image of the EGFR bispecifics for a very similar population in the frontline. We have peto plus Pembro at about 50%, far less than what they're achieving in the HPV negative population. More recently, BioAtla published their data in Frontline, including their efficacy with KEYTRUDA in HPV positive patients coming in at a modest 27%. Very quickly, just to dive into cervical cancer, this will be our Friday oral presentation.
A reminder that here is another HPV-positive or HPV-driven tumor type, similar to oropharyngeal head and neck. The bar to beat here is an existing drug. This is Tivdak, previously from Seagen, now at Pfizer. It is an MMAE-armed ADC targeting tissue factor. Tivdak is limited by two things. It has a relatively modest efficacy at an ORR of about 17.8%, and it is hindered by a number of very challenging toxicities. Like us, it has ocular toxicity. As do a number of these ADCs, as I've mentioned, ourselves, Tivdak which, of course, is approved, ELAHERE, which is approved, and of course, LEQEMBI, which has similar toxicities but at much higher levels. Tivdak is also hindered by things that we don't have with CRB-701: high rates of peripheral neuropathy, bleeding, and skin toxicity. This is our waterfall plot for CRB-701 in cervical.
Again, a dose response, as we saw in oropharyngeal, with a top dose delivery confirmed ORR now of 34%. That's effectively twice the efficacy we have seen with TIVDAK. Then a durability that, again, like oropharyngeal, is still ongoing but has already reached eight months for the top dose, with a PFS that is catching up. So just to put that into context on slide 32, you can see where we line up versus TIVDAK and for that matter, chemotherapy and second-line monotherapy, which will be one of the other physicians' choices. So far, we are certainly looking like a drug with a very attractive profile for this. With that, I'm going to turn it over to Dr. Hanna. I've got a few questions for Dr. Hanna that I suspect many of you have already. After that, we will turn it over to our audience.
Dr. Hanna, good morning. Thank you for joining us early this morning. I think my first question, which I'm sure is on people's mind, is just a brief background on what is oropharyngeal cancer, how do you define it, how many patients are there, how do they differ from other head and neck patients, et cetera?
Thank you all. Happy to join the conversation. It's exciting to see, again, drugs moving forward in the advanced head and neck cancer space beyond the momentum that has been ongoing for the novel EGFR inhibitors. I've been waiting patiently for the antibody drug conjugates to surface in sort of the next generation of advanced trials for these patients. I think oropharyngeal cancer in general, as you outlined in the beginning of the discussion, is an anatomical distinction of sort of the back of the throat. We think of the tonsils, the base of tongue, sometimes the lingual tonsil or the back of the tongue tonsil and soft palate as making up this sort of area where HPV likes to hide.
As you said, about 85% of oropharynx cases, particularly in never smokers and in the United States, would be attributable or causal related to HPV virus, the highest subtypes being 16, 18, 31, 33, 35, et cetera. We define it largely by a clinical constellation of features. Generally, it often has a predilection for men, as people know, 5 to 1 against women in terms of incidence. We know these are often limited or never smokers, although that can be variable in some instances. They typically are people in their 40s to 60s, although there's some variation there, and that's based on the lead time that it takes for the HPV virus to set up shop in the back of the throat and then lead to changes over time that result in cancer or neoplasia. All of that together sort of defines the HPV-positive patient.
These patients, therefore, compared to HPV-negative patients, tend to be younger, they have less risk factors or carcinogen-based risk factors, and there is sort of a socioeconomic distinction between these patients if you look at demographics and in parts of the world where these patients are most present. Certainly, we have a large catchment in North America as well as in the United States, specifically. I think important, as you pointed out, the trends in the biology of this disease suggest that we're going to continue to see a rise in more of these cases. An elegant question I often get is how is current vaccination, preventative vaccination, impacting these rates? These rates are still going to rise, likely projected through 2040, all the way through and plateau in 2050.
That's another 25 years, and that's because of the lead time in requirement for getting kids between nine and 26 vaccinated, and the time it will take to see epidemiologic shifts in cases. We're not going to see any slowing of cases, at least through 2040 or 2045, based on current predictions, and I think that's really important for thinking about who might benefit from a drug like CRB-701.
Dr. Hanna, on paper, as it were, the data shows us that it seem to be North America and Europe, it's about one in two patients in these studies. Recently, you shared with me some interesting anecdotes around real-world data you're seeing or experiencing in your practice around how many of these patients are walking in through your door, as well as some of the age distributions. We know that they're younger, you referred to it. I think you shared with me an anecdote that frankly surprised me around how young they can actually turn out to be.
Yeah, that's the case. I actually just last week, met a gentleman from the South who's 31 years old with recurrent metastatic HPV-positive head and neck cancer. That just gives you a sense of the lower bound of the age range for some of these patients, and we see patients in their 70s and 80s. I would say, it's particularly at a place like ours at Dana-Farber in Boston, where we have a pretty large New England-based population catchment. We do see a large percentage of patients with HPV-associated disease. As I was sharing with you, I would estimate that our group is probably seeing, on average, five to six new cases a week of curative or definitive head and neck disease related to HPV.
Perhaps, if you take all of our patients over the course of several months, I would say that in some instances, it's almost 50%-70% of patients that are in our clinics have HPV-associated disease. There's going to be some regional and geographic variation, and especially at our center, whereas, maybe at our public hospital down at Boston Medical Center or across town at Mass General Brigham Cancer Institute, there might be some variation. In general, we are seeing a large number of these patients, particularly in urban cities along the East and West Coast, which fits with how quickly the CRB-701 experience and trial has been able to recruit patients with oropharynx and HPV-associated disease with a small number of sites.
I think, a really important point as we think about enrolling a confirmatory registrational trial, there is no shortage of patients in need with HPV-associated disease. Remember, about upwards of 20% or even 25% of all HPV head and neck cancer patients will eventually require advanced metastatic treatment and develop, sadly, either local regional recurrence, persistent disease, incurable or metastatic disease.
One of the paradoxes out there is there are these two competing notions. One is there is a very meaningful population of these oropharyngeal HPV-positive patients. The other one is we have the rise now of these very exciting EGFR bispecifics, and that are generating a lot of excitement and interest. Yet it looks as though the oropharyngeal or HPV-positive patients are being left out of that. Maybe help us understand what is the challenge here with the EGFR bispecifics, and then drawing from that, what is the unmet need if one is an oropharyngeal patient?
Yeah. I think you're highlighting what I've been thinking about over the last year as petosemtamab, which is an EGFR LGR5 bispecific, and ficerafusp alfa, as you know, the EGFR TGF-beta trap, have come into clinic. Now amivantamab sort of catching up quickly, this EGFR c-Met bispecific. Largely, the data is very clear that EGFR signaling is most critical in HPV negative biology or carcinogen-driven biology. It is much less of a biological entity in HPV-associated disease, which is driven more by early proteins E6/E7 and modulation of things like RB and P53.
I think you made an important point that if any of these trials or all of these trials in the first line, whether it's FORTIFY or the LiGeR-HN trials or the OrigAMI studies, are all positive or some are positive, we're going to be looking at a new paradigm in treating HPV negative disease with these novel EGFR therapies. That leaves a wide open gap and for the rising and increasing incidence of HPV positive patients that we're seeing. I can tell you, it's much easier to enroll HPV positive patients just because there are so many less trial options for these folks. As you highlighted, the need is growing. If 20%+ of those patients develop advanced disease or incurable disease, you can see how the numbers are continuing to rise.
I would just sort of focus on peto for a second, because as you said, while it's not confirmed in the trials, both the first and second peto studies, or sorry, monotherapy and second-line and the combination IO plus peto trial in first-line, did enroll a percentage of patients with HPV positive disease. They're confirmatory studies, roughly 30%. It's not clear that they will observe a robust signal in that population for benefit. It may be that the agency, the FDA, decides in the end that there is not enough data or patients to justify a label that includes HPV positive disease. If that is the case, that will make even more of a wide-open space beyond EGFR targeting for patients with HPV positive disease, who right now have pretty limited options after the first-line, our traditional pembrolizumab chemo option.
That puts us in a position where second line, we're relying on garden-variety, old school chemo taxanes, 5-FU methotrexate type drugs, prioritizing clinical trials. Huge developing unmet need. This trial is coming. This phase III trial TEMPO-1 is coming at a very critical time. We talked a little bit about or highlighted the unmet need here, the encouraging efficacy we're seeing. There is a price to pay with this drug, and that is the ocular toxicity. Can you contextualize that both in terms of how you're dealing with it, in terms of your familiarity with ocular tox as an oncologist, and contextualizing also the impact on the patient and what is at stake for the patient at that stage of their disease? I think this is a really important point.
First thing we have to acknowledge is who this patient is and before we talk about the ocular toxicity. This is a patient with an incurable, recurrent metastatic cancer who is going to unfortunately cease to succumb to that cancer at some point without meaningful cancer-directed therapy. With that palliation comes the notion of what toxicities we're willing to accept to extend one's life and to minimize a disruption of quality of life. Let's just be clear about that when we're talking about, yes, there's ocular toxicity, and anything that mentions vision can be a concern. We need to realize that these are incurable patients who have already failed immunotherapy and/or chemoimmunotherapy, and we're trying to extend their life, hopefully by many months, if not years.
Having worked with this drug now for quite some time, I think the first thing to realize is that this does seem to be a reversible problem. While we counsel patients that they may have some issue related to blurry vision or difficulty seeing while driving, for example, that may disrupt function for a period of time, with appropriate monitoring, holding of drug intervention, and interception with certain eye drops, this is a reversible process. As you said, we thankfully have not seen significant persistent long-term effects that we're aware of at this point. I think that's important. I think the other thing to recognize is there are a number of other toxicities related to antibody-drug conjugates as a class, which I've worked with many of them now over the last several years as they've tried to move forward in head and neck.
There's no free lunch here. These patients, there is some toxicity issue associated with a number of these drugs, and you highlighted some which are less of a concern for CRB-701, but extensive peripheral neuropathy is often irreversible and can result in significant mobility issues and daily activity of daily living disruption. That's something that patients need to be aware of. Significant skin toxicity can be an issue. pneumonitis or lung inflammation resulting in discontinuation. Again, we're not seeing those things, and these vision issues tend to be manageable. They do mitigate with drug hold. We have, thankfully, routine availability of ophthalmology. I think that's the other important thing. We haven't run into issues with being able to refer patients to different venues throughout the city. For example, at our site, who can help to manage and monitor these ocular changes, because sometimes there's not even visual symptoms.
It's just the beginning of monitoring changes on an eye exam, for example, where there might be mild corneal inflammation, and we want to be vigilant with eye drops, for example. Again, with a few eye appointments and integrating eye drops, generally, patients are able to continue on drug, sometimes have to dose reduce, but able to maintain or resume dosing and demonstrate efficacy and benefit from the agent. I think that's the clear message I would make. I think the other key point I would say about the ocular toxicity in general is that for most of these patients, when talking to them about pros and cons of different drug therapies, they seem to be very willing to participate in doing the eye care up front and using eye drops preventatively, keeping their eyes moist, et cetera.
I think patient engagement has been a positive signal for how we're able to handle this. The last thing I would say is I would remind the investors and those listening, there are ADCs on the market that already have ocular toxicity warnings. I sometimes use off-label datopotamab. We just got another approval for datopotamab in the breast cancer setting, now also in lung cancer. There's a required ocular exam prior to start. There is a well-established 25% rate of grade 1 to 2 ocular toxicity with that agent, and it seems to be something that patients can manage and that drug is on the market. I do think we also want to contextualize the sort of placement of this drug outside of just head and neck cancer and in the broader ADC-approved landscape.
Thank you. Very, very helpful. Let's turn it over to our audience and operator, if you could go ahead and start the Q&A session, please.
Certainly. We'll now be conducting a question and answer session. If you'd like to be placed into question queue, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue, and you may press star two if you'd like to remove your question from the queue. Once again, that's star one to be placed in the question queue. Our first question today is coming from Brian Abrahams from RBC Capital Markets. Your line is now live.
Thanks so much for taking our questions. Just two from me. I guess first, it sounds like the ocular toxicity continues to be pretty manageable overall, but I was wondering if you could elaborate a little bit more on the overall safety, including the ocular tox by dose at the 3.6 mgs per kg dose, and by the subpopulations. Secondly, just on the TEMPO-01 phase III, can you maybe talk a little bit more about the mechanics of that study? Just how the interim analysis will work, when you think that might occur, what the bar would be for the primary accelerated approval endpoint on overall response, and just maybe a little bit more about that study design. Thank you.
Morning, Brian. Thank you. Let me start and then, Dr. Hanna, if you have anything to add. On the dose by dose, we have that in the poster. There are certain things that we'll wait till the poster comes out. It is smaller numbers. I will say that overall, it's the same pattern. It also doesn't seem to be tumor specific, which is encouraging. I think on Vistic already, Brian, we gave a breakdown of specifically of the discontinuation and interruptions, for the 3.46 for ocular, specifically as a dose. For TEMPO-01, we'll give you more updates at ASCO and shortly after. Again, we're just waiting for the final protocol approval from FDA. Once we have that, we will share that with you.
We'll also share with you the specifics of what is the physician's choice, although I don't think it's particularly exotic, as you can imagine, for example, it's highly unlikely that it'll be TAXOTERE in this population. Dr. Hanna, is there anything you'd like to add at this stage?
Yeah, I would just say to the first question, as Yuval points out, without saying too much, table two, which will be in the poster that's released this week, specifically addresses the question of dose-related ocular toxicity or keratitis. There's a column that outlines the rates by dose level, so you'd be able to compare that to the total rate that was shown in the deck to you today. I would say for the second question around the design of the trial, I will say this is a trial that's involved a number of key opinion leaders, including myself, and I think without saying much about the specifics, I would argue that the bar is probably generally pretty low because you're thinking about a population where they've already been through chemo immunotherapy.
There's no standard agreement or preferred regimen in the second and third-line, which the TEMPO-1 study would address as the comparator. The traditional response rates, it's hard to know for HPV-selected patients because years ago when these drugs were being defined as second and third-line options, we didn't tease out HPV-associated disease at that point in time. I would argue that the response rates benchmark for most of us sits around 20-ish% to even maybe a high end of 25%. That sits pretty low. That would be the bar in general for a second and third-line recurrent metastatic head and neck trial. I think welcoming an ADC versus investigator choice design is very much on brand with what one would expect for a drug like this moving into registration studies.
That's really helpful context. Thanks again.
You're welcome.
Thank you. Next question today is coming from Paul Chang from Guggenheim Partners. Your line is now live.
Hey, good morning. Congrats on the nice update, thanks for taking the question and providing all the helpful commentary. For the head and neck data, understanding it's early days, is there anything you can say about how survival is trending and specifically have you seen enough durability on that front to finalize your powering assumptions for the phase III? Related, how do you think about the control arm bar for survival in oropharyngeal patients? Then I have a follow-up.
It is in that sense early days, although what we're seeing in terms of DCR and TSS is certainly encouraging for that. Paul, I think we're just going to have to wait and see how that matures. The powering assumptions, again, Dr. Hanna has been very helpful with his comments. Remember if I may, what we saw, for example, and this is a little bit of speculation, what we see, for example, in Peto second-line monotherapy is a larger study, but remember that they chose to address all comers. In other words, they have a population that is a mix of HPV negative where they will see strong responses
HPV positive where we know that their responses are not as strong and that could create a certain amount of "drag." We've chosen philosophically to do something that's much more similar to what Vikara and JNJ are doing in their frontline setting, which is to focus exclusively on that one half of the population where we see strong responses and not an effort on another half of the population where we are very unlikely to bring benefit. Dr. Hanna, anything you'd like to add to that?
I think what you're getting at is a great question. I would argue that early clues to the OS benefit is going to come from the durability in PFS, which Yuval highlighted nicely. That PFS for the 2nd, 3rd-line plus median 3-line or more population with CRB-701 is around six months at the preferred 3.6 dose. That bodes well for an advanced population. When you think about, again, not necessarily for this particular drug, but in general, when we think about median OS for a 2nd, 3rd-line population, when we've looked at the follow-up data to KEYNOTE-048 from Dr. Harrington, looking at second PFS2, so to speak, and survival after exposure to chemoimmunotherapy or IO. Trials are hovering around median OS of eight to 10 months.
I would say that's the range we're interested in terms of recognizing that this is also going to be an oropharyngeal population where we need to maybe do a little bit better on the higher end, just because these patients tend to do better with all treatments we give them as compared to an HPV negative patient, even in this setting. All of that's being accounted for and has been accounted for in the registrational design of TEMPO-01. That just gives you some numbers to start to chew on in terms of what we would project for median survival improvement, or sorry, median survival and what we would need to improve upon with the CRB-701 experience.
Got it. Thanks for that. Maybe a quick follow-up for Dr. Hanna. When you think about the provider base that may be treating patients with 701 in the real world, how attuned are you and your peers to a paradigm that bisects by oropharyngeal versus non-oropharyngeal? Currently, is that smoking status a factor that might dictate, for example, EGFR use, or is there some degree of education that's got to happen on that front?
No, I think that's pretty well established. The narrative around HPV causality linked to oropharynx has pretty much the entire head and neck community, and I would say the oncology community in general, even general oncologists who dabble in head and neck, are comfortable with oropharynx versus not. I actually don't think it will be an issue. This is not a new designation. This is not a new way to separate apples and oranges. I think that should be very clear for the oncology community.
Got it. Super helpful. Thank you very much.
Thank you both.
Thank you. Our next question is coming from Amin Makarem from Jefferies. Your line is now live. Hello, Amin. Your line is now live.
Hi. Thank you for taking our questions. A couple questions from us. First, I have a question for Dr. Hanna on patient selection. How straightforward is it to distinguish oropharyngeal patients versus other subtypes of head and neck? Are there clear boundaries there, or are there gray areas when assigning patients? I have a follow-up.
This dovetails on the last question. It's actually pretty clear. When we see patients in clinic and we review scans and we look with an endoscope, a nasopharyngoscopy exam with a camera flexible scope, it's pretty clear that a patient is presenting with a base of tongue primary, which is exophytic and sort of sitting in the back of the tongue or arising from the tonsil. You can even feel this location if you palpate induration around the tonsil. Believe it or not, these anatomical distinctions are pretty straightforward and often correlate clinical exam on our endoscope and our physical exam with what we see on CT imaging. You take into account the fact that usually the demographic and clinical characteristics of the patient align with those physical findings. As we said, limited never smoker, often in their 40s to 60s, predilection for males.
Just for you all, in initial stages, most men present with, or HPV patients or oropharynx patients in general present with a sort of cystic enlarged neck node which is ipsilateral or on the same side as their primary. That's sort of like a bread-and-butter classic presentation. I don't see any concerns with delineating patients anatomically and clinically based on those findings. I think it should be quite straightforward for our community.
Helpful. Thanks. For the TEMPO-01 study design, it includes an adaptive feature for interim analysis and sample size potential re-estimation. What do you think there could be a need for a sample resizing?
Dr. Hanna, go ahead. You were very helpful in that protocol design.
Yeah. I think it's very prudent to have an interim analysis that's assessing response rate. I think for garnering enthusiasm and making sure that we're seeing what we want to see in terms of the phase III component of things as compared to our experience in this growing phase I, which almost feels like a phase II now with dose selection at 3.6. I think we would, as I said before, ideally look for response rates in the second-line advanced head and neck cancer setting for recurrent metastatic disease around that sort of 20%-25% range.
I think the details of the protocol are still being finalized, but if that were to be the case with an acceptable confidence interval, we would then also look at the PFS and OS signal for that first group of patients and then decide, do we need to increase the number of patients in the study to therefore tighten up the power or the signal for an improvement in OS? I think it's an opportunity. It's an opportunity to pause, make sure we're not seeing any new safety concerns, making sure that our phase III experience is doling out what we were expecting in terms of hitting response rates as compared to that initial phase I that we're doing. Make sure that we feel like we have enough patients to adequately assess the power related to an improvement in OS.
This is fairly standard, as many of you know, for contemporary phase III registrational studies. I know that FORTIFY is doing something similar, or did, around its dose selection. Certainly PDL is doing something similar and recently added patients to both their phase II and phase Is.
Helpful. Thanks.
Thank you. Our next question is coming from Jeff Jones from Oppenheimer. Your line is now live.
Good morning, guys. Really appreciate the additional detail here this morning. I guess two questions from us. Can you speak maybe mechanistically, a little bit more to the difference in effect you're seeing in the HPV-positive patients? You mentioned Nectin-4 expression levels, and maybe how you think about that impacting patient selection for the phase III biomarkers and/or subgroup analyses. Curious how you're thinking about first-line, given, as you mentioned, the PADCEV KEYTRUDA data, and how that might impact your thinking about second-line down the road or moving ahead into first-line. Thanks.
Thank you, Jeff. Mechanistically, it fits nicely with a number of things. It's very similar conceptually to the dynamic of cervical cancer, right? We've known that this is one of the richest Nectin-4 tumor types out there, as is cervical. Remember that our very strong preference to date has been not to explore this ADC in bladder, simply for market reasons, commercial reasons. The other thing, Jeff, that I think will be helpful for the audience to realize is, if possible, we would rather avoid a companion diagnostic approach. We would rather avoid having to do a biomarker selection in any of our tumor types. A reminder that is what PADCEV managed to avoid doing in bladder, because bladder is so Nectin-4 enriched that there was really no rationale for having a specific CDX built into it.
In cervical, something like 98% of these women are HPV positive, and in head and neck, oropharyngeal cancer, as we heard today, and we've seen today, both our data sets, as well as the literature indicates something like 80%-plus of these patients are positive. What we prefer to do is the anatomical selection and focus on that. What we've heard from Dr. Hanna and other of our clinicians and KOLs is that is also their strong preference. As you can imagine, this was also a subject of discussions with FDA around that path forward. Dr. Hanna, anything to add to that?
Yeah, I think I would just add a little bit more scientific color there. Nectin-4 is a cell adhesion molecule. It belongs in the family that allows epithelial cells to junction or remain tight. You think about that as being important at the intersection of cells breaking off and leading to metastases. Nectin-4 does play an important role, and there's biology that suggests that it's linked to viral transformation, how epithelial cells differentiate, and also that invasion metastasis question. It's been shown to be able to activate things like PI3K signaling, which 30% of HPV-positive patients have, as well as Wnt/β-catenin signaling. It's also been important in promoting proliferation and motility and epithelial-mesenchymal transition. I think all of that serves pre-clinically to strengthen the relationship between Nectin-4 and HPV.
Fundamentally, the two points clinically I would comment on is that Nectin-4 is a validated target. Many of the patients enrolled for the initial Astellas Pfizer study with EV were HPV positive, and there were response rates, as you all know, in combination with pembro, but also as single agent, as published in the JCO experience. That's now in the guidelines. We know this is a validated target in this population. Then, as you've all said, we have another candidate example of HPV-associated cancer in cervical that's showing nice response rates.
I think all of the totality of that data serves to strengthen its role for HPV cancer. I would say for the second question around avoiding a companion biomarker, I think that is a smart move for a number of reasons, not just financial or from a regulatory standpoint, but there are a couple of arguments as to why you would not want to restrict. When we're running this large TEMPO study, one of the things that could disrupt enrollment, dissuade enrollment, or complicate patients getting on is requiring central testing in real-time for something like P16 or HPV. P16 testing is done at many labs. It's CLIA certified, but not every institution outside of some of the major academic institutions rely on HPV confirmatory ISH or PCR testing to show viral association. Remember, P16 is just a surrogate marker for HPV. It does not imply viral causality.
If you slow a trial down by requiring central testing, you're going to disadvantage patients, you're going to have dropout, you're going to have issues with delays to getting patients on when we can collect that data and check HPV and P16 status ad hoc or as a secondary analysis in the end. We know that the vast majority of these patients, 85+% will have HPV-associated disease in the end, and we'd rather not slow that enrollment. That would perhaps complicate a label. There's no preferred assay, right? People use whatever assay their institution prefers. P16 IHC can be done in a number of CLIA labs, but HPV testing is not unified or central. You can do ISH probes towards several probes. You can do PCR testing.
If we introduce that element of complexity, I think it would be a disservice to the patients and slow the trial down. I think those were some of the fundamental reasons behind an anatomical designation for eligibility as opposed to a laboratory or biomarker companion.
Jeff, just to your second question on frontline, second line, with that, we're going to have to wrap up. What we are emulating is both what PADCEV did in bladder and what peto is doing in head and neck. We start with second line where we already have data, it's actionable. It seems like a very attractive commercial opportunity. We move forward with that is the indication that we'll be first to market if all goes well. Then we also explore frontline as PADCEV did and as peto did. In the frontline setting, we'll see what the data looks like early next year. If the data looks encouraging, and again, we have this precedent of PADCEV, then it'll be very sensible to trigger that as well, knowing though that that is a larger and more longer study than the second line.
It may actually eventually end up eclipsing the second-line indication the same way that these days, for example, very few patients in bladder get PADCEV as monotherapy in second line. It really is all about now frontline plus pembro. That takes time, and it's a much larger effort. Being able to plant the flag as peto is initially in second line will have some very important commercial ramifications.
Can I just add, Nikhil?
Yeah, go for it.
I just want to say that I would second everything you just said. To jump into first-line with a combination right now, regardless of the HPV signal, would be not the appropriate place or the highest unmet need. The highest unmet need is beyond chemoimmunotherapy and IO, where this single agent drug by itself could become an established standard of care for these patients, and replace sort of the outdated and historical controls of chemotherapy and less ideal agents. We in the KOL community are very supportive of pursuing the second, third-line option first.
Thank you for that.
Greatly appreciate that. Thank you.
Thank you, Jeff. With that, I'm going to wrap up. I'm sure there'll be lots of follow-on questions. I look forward to seeing, I hope everybody, starting on Friday at ASCO. A reminder, Friday, sort of late afternoon is our cervical oral presentation. The next day we have the poster. That poster should go live that morning. Of course, we'll put everything on our website as well. Last but not least, our breakfast KOL event on the Monday morning, bright and early at 6:30 A.M. Chicago time, with Dr. Hanna, Dr. Perez, and Dr. Rosenberg.
I'd like to thank Dr. Hanna for his time this morning and for all the hard work he's been putting into this program, as well as, of course, thanking other clinicians, healthcare workers that have been part of this study, and the Corbus team, of course, and last but not least, of course, the patients themselves. Thank you everyone, operator, it's over to you.
Thank you. That does conclude today's teleconference webcast. You may disconnect at your line at this time and have a wonderful day. We thank you for your participation today.
Thank you so much. Bye-bye.
Thank you. Take care.