Webcast: https://event.choruscall.com/mediaframe/webcast.html?webcastid=VEzQVRmI
Participants
- Frank Bedu-Addo, Chief Executive Officer
- Lauren V. Wood, Chief Medical Officer
- Matt Hill, Chief Financial Officer
Frank Bedu-Addo, Chief Executive Officer
Thanks for joining us today to review the updated interim data from the Versatile 002 clinical study in recurrent or metastatic HPV16-positive head and neck cancer. The data was presented at the 2023 ASCO Annual Meeting yesterday. It should be noted that the data presented yesterday was the same data released by PDS Biotech on May 25, 2023. No new information was presented.
Before I start, I would like to remind you that based on all our ongoing Phase II PDS trials, we have reported efficacy data from over 90 patients. In addition, we have reported safety data in over 120 patients. The data has been generated at over 30 clinical sites in four separate studies, including our Phase I monotherapy study. The anti-tumor, immunology, and safety data continue to be consistent across trials, multiple sites, and multiple HPV cancer indications.
At PDS Biotech, we are seeking to provide improved treatment options that are tolerable and that extend patients' lives. Here you see some of the agents that constitute the current state of the art in treating recurrent or metastatic head and neck cancer. I would like to point out that there have been no randomized head-to-head studies comparing the combination of PDS 0101 and Keytruda with Keytruda monotherapy or Keytruda plus chemotherapy.
We will only provide published data and information as a reference. This slide summarizes the efficacy and safety of the current standards of care against which we are benchmarking the PDS 0101-Keytruda combination.
In the Keynote 048 published results, Keytruda monotherapy results in an objective response rate of 19% and a 12-month survival rate of 50%. It is also reported in the Keynote 048 published results that Keytruda plus chemotherapy results in an objective response rate of 36% with a 12-month overall survival rate of 65%.
The median overall survival for Keytruda and Keytruda plus chemotherapy are 12.3 months and 13.6 months respectively. Our ultimate goal is not only to improve the objective response rate but ultimately to extend patients' overall survival. In head and neck cancer, objective response rates to date have not translated to overall survival.
It must also be noted that for Keytruda monotherapy, it is published for Keynote 048 that 17% of patients had severe Grade 3 or higher treatment-related adverse events. With Keytruda plus chemotherapy, the Grade 3 or higher severe treatment-related adverse event rate was 72%.
As a reminder as to how PDS 0101 works, PDS 0101 as a monotherapy and in combination with other agents promotes the induction of high levels of the right type of CD8 killer T cells in the right quantity and with the right tumor killing potency. This promotion of multifunctional T cells plus the HPV 16 specific memory T cells we believe enables PDS 0101 to achieve durable clinical responses with prolonged patient survival.
It is important to note that achieving prolonged survival with a well-tolerated regimen has been one of the most critical limitations of cancer therapy. Our goal by combining PDS 0101 with Keytruda is to increase the percentage of patients who respond to therapy and to enhance the long-term survival of the patients without compounding the toxicity of Keytruda monotherapy.
The inclusion criteria for Versatile 002 requires patients to be PD-L1 positive with a CPS score of 1 or higher and all patients must have HPV 16 positive cancer. HPV 16 positivity represents 60 to 65% of advanced head and neck cancer. The primary endpoint for Versatile 002 is best overall response, BOR, of confirmed complete response, CR, or confirmed partial response, PR, per RESIST 1.1.
Key secondary endpoints are progression-free survival, PFS, overall survival, OS, and safety and tolerability. We announced this past May that we completed enrollment of the full cohort of 54 immune checkpoint inhibitor-naive patients. Patients receive Keytruda by IV every three weeks for 35 cycles or until disease progression, death, or stoppage due to toxicity. PDS 0101 is given by subcutaneous injection every three weeks during the first four cycles only and again at cycle 12 for a total of five doses.
Now let's discuss the study's updated interim results. We presented efficacy data on the modified intent to treat population of 34 patients. These are the patients who have received at least one dose of the combination and who have also had at least one imaging scan post-treatment. This doubles the patient size compared to the data presented at ASCO in 2022. Let's take a look at the patient disease control and the impact of PDS 0101 administered in combination with Keytruda on tumor shrinkage and stabilization to date.
This waterfall plot shows that the majority of patients, about 68%, experienced tumor shrinkage. To date, 70.6% of the patients have disease stabilization or tumor shrinkage. 41.2% of patients have a confirmed or an unconfirmed objective response. 44.1% of patients have disease stabilization and 26.5% have progressive disease. Do note that one of the 34 patients was not available and is therefore not shown on the plot. However, to ensure that our data is not overstated, 34 is the number used in the denominator to calculate the percent response rates.
Let me now explain what we mean by a confirmed or unconfirmed objective response. An objective response occurs when a patient has tumor shrinkage of 30% or more. Patients on the trial receive a scan to evaluate their target tumors every nine weeks. To determine a confirmed response, we adhere to the RESIST 1.1 criteria for best overall response, meaning that if a patient is determined during their scan to have stable disease, partial response, or complete response, this result will be confirmed on the subsequent scan nine weeks later.
And at that point, the patient will then be deemed to have a confirmed stable disease, partial response, or complete response. If the patient has improved from stable disease to partial response on the subsequent scan, that partial response will again have to be confirmed nine weeks later on the subsequent scan.
The unconfirmed patients are the patients who were seen to have a partial response or complete response, but who have not yet received their subsequent scan nine weeks later. Also important, if a patient had, for example, 90% tumor shrinkage, and nine weeks later, an increase in size of 20% is seen over that 90%, even though the tumor size is still significantly below the 30% threshold, that increase of at least 20% over the best observed results will lead to the patient being characterized as having progressive disease. This is what you see with the two patients who are denoted in red, who have tumor shrinkage of about 40% and 70% respectively.
It should be noted that the waterfall plot does not capture the durability of responses, which we will now discuss on the Kaplan-Meier plot for progression-free survival, or PFS. The PFS essentially measures the effectiveness of disease control and how long tumor shrinkage or stabilization continues before disease progression occurs. Here you see the Kaplan-Meier plot showing the calculated median PFS of 10.4 months, with PDS0101 administered in combination with Keytruda.
As I showed earlier, the PFS published in the Keynote 048 study for Keytruda Monotherapy and Keytruda Plus Chemotherapy are 3.2 months and 5 months respectively. What we believe is notable about this PFS result is the compelling durability of the anti-tumor response.
Now here you see the Kaplan-Meier plot for overall survival for PDS0101 administered in combination with Keytruda. In this curve, you see here there's a minimal decline towards the x-axis due to the fact that we have only seen four deaths to date, and approximately 90% of the patients continue to stay alive. As a result of the continued high survival rate of the patients, we have still not reached the median overall survival for the combination. However, we are pleased that the calculated 12-month overall survival rate is 87.1%. As I showed earlier, the 12-month overall survival rate published in the Keynote 048 study for Keytruda Monotherapy and Keytruda Plus Chemotherapy are 50% and 55% respectively.
The spider plot shows the patient's anti-tumor response with time and the rates of tumor shrinkage and progression. The key takeaways here are the following. The majority of patients see tumor shrinkage and therefore are below the baseline. Also, the majority of patients with tumor shrinkage start to respond quite rapidly within about 60 to 90 days. In our Phase 1 monotherapy study of PDS0101, we found that high levels of multifunctional HPV16-specific CDHT cells were induced within 14 days of PDS0101 subcutaneous injection, and we believe the rapid response rate of tumor shrinkage in Versatile 002 is consistent with this observation. This response rate is also consistent with the results in locally advanced cervical cancer.
Dr. Anne Klop at MD Anderson reported at SITC in November 2022 that 100% of patients treated with PDS0101 in chemo radiation had an objective response by day 60 with tumor shrinkage of greater than 60%, and 8 out of 9 patients had a complete response by day 170. Also, we can see that a number of patients are having a durable response in that the trajectory of their tumor size curves is staying flat below the baseline and extending beyond 500 days. This result of the observed durability of the clinical response appears to translate to prolonged overall survival.
As we look at the swimmers plot, it shows the survival of each patient over time. Most notable in this plot is that several patients are approaching two years of survival, and we have seen very few deaths to date with almost 90% of the patients still alive. As I mentioned at the start, we have not compared the combination of PDS0101 and Keytruda head-to-head with any agents in a controlled study. This slide is simply to put the results generated to date in perspective based upon the published results for the state of the art in recurrent metastatic head and neck cancer.
So how are we doing when it comes to tolerability of the combination? With safety, we have evaluated the full intent to treat population of 48 patients. Many patients see mild to moderate injection site reactions and fatigue as their main side effect.
Only four patients out of the 48 have had treatment-related Grade 3 side effects. There have been no Grade 4 or 5 treatment-related adverse events. This is highly encouraging and in agreement with the feedback we have received from several investigators regarding the quality of life experienced by their patients on the combination and the tolerability of the treatment. To date, no patients have left the trial due to treatment-related adverse events, which is very encouraging. To date, PDS0101 does not appear to compound the known toxicity of Keytruda.
To understand how the clinical results and outcomes are evolving as we enroll more patients, we compared key outcomes that were reported at ASCO 2022 for the first 17 patients with the results presented at ASCO 2023 in 34 patients. The analysis shows that the results have remained practically identical and have stayed consistent as more patients have been enrolled.
The promising combination of prolonged overall survival and tolerability of the combination we believe warrants rapid progression to a controlled registrational trial. As we announced recently, we plan to initiate Versatile 003 in the fourth quarter of this year.
As mentioned previously, we have successfully transferred our manufacturing of PDS0101 from our clinical manufacturer to our commercial manufacturer, and the Phase III clinical product has been successfully made and released for use. We expect to file the amended IND in the third quarter of this year, start qualifying sites with the goal of activating 90 to 100 worldwide sites. We plan to initiate the trial in the fourth quarter of this year.
Again, this will be a randomized controlled trial and is being powered for overall survival and progression-free survival as the primary endpoints. We anticipate having two interim analyses which may provide the opportunity for early discussions with the FDA regarding possible accelerated approval pending on the results.
To conclude the ASCO presentation overview, PDS0101 continues to provide strong proof of concept for the Versimmune platform across multiple Phase II studies. We have efficacy data from over 90 patients to date. Importantly, the anti-tumor, biomarker, and immunology data have shown strong consistency and correlation across all types of HPV cancer and at all studied stages of the disease. There has been a strong agreement between preclinical and human results, which we believe is primarily due to the technology's mechanism of action leading to clear translation between preclinical and human clinical results. We look forward to continuing to update you on our progress, not only on Versatile 002 and 003, but also on our other PDS0101 clinical programs.
Additionally, our antibody-conjugated and tumor-targeted IL-12 PDS0301 Phase II pipeline is being studied with standards of care in various solid tumors.
In closing, I would like to take a moment to address a situation that occurred yesterday, mainly in social media, where certain data from the poster presentation were mischaracterized and untrue assertions were directed at our company.
Rather than going into a point-by-point discussion of what was posted or the corrections and apologies that were later issued, I want to use this opportunity to assure all of our
stakeholders that PDS Biotech is an ethical company that takes great care in communicating data from our clinical trials. We strive to present information accurately, objectively, and in great detail in order to minimize the chance for misunderstanding, and because it is the right thing to do considering we are in the business of developing medications that one day will hopefully benefit people who are in the direst of circumstances.
What happened yesterday was unfortunate on several levels, but thankfully, I believe the impact will be short-lived. These data as presented yesterday and discussed this morning are quite promising, and we are highly optimistic about the opportunity to initiate the birth style 003 trial later this year. At this time, I will hand the call over to the operator for the question-and-answer session. Thank you.
Question-and-Answer Session
Louise Chen - Cantor Fitzgerald.
Hi. Congratulations on the data at ASCO, and thanks for taking my questions here. I have three for you. First, where do you think this versatile 002 median overall survival will shake out, and why do you think that?
Secondly, how is the reception at ASCO due to the presentation of your data?
The last one is just on your versatile 003. What would you consider a win in overall survival and progression-free survival in that study? Will there be any differences in terms of the patient population you enroll, and how quickly do you think this trial will enroll? Thank you.
Frank Bedu-Addo, Chief Executive Officer
I will start with question number 1. I'll hand over to Lauren for the second question regarding the feedback at ASCO yesterday. I'll address questions 1 and 3 and then hand over to Lauren.
For versatile 002, where do we think median overall survival will shake out? Well, the data we have today is extremely encouraging in terms of the fact that patients continue to live and have a sustained survival. It is difficult to predict how long the patients are going to live.
I think one of the key reasons why we – there was a gap of duration between when we had our meeting with the FDA regarding moving into Phase 3 and designing the Phase 3 clinical trial is that we had really no visibility to what our PFS was or what our overall survival is going to be. Currently, based upon the fact that we have the 12-month overall survival rate versus what we are comparing – what we will be comparing PDS-01 against, we're able to understand what the potential hazard ratios may be, and therefore, we gain some level of comfort in designing those statistical endpoints.
But I think all I can say at this point is we are extremely encouraged by the high rate of survival we are seeing, which we believe translates very well based upon what we saw in our preclinical studies and what we are seeing in other studies. For example, the triple combination that was run by the National Cancer Institute. Again, we've seen very strong durability of responses there. And very similarly with this data that was presented by MD Anderson at SITC. So, this prolonged survival is consistent among the trials that we're running with PDS-01. So, we will continue to follow these patients and continue to update the markets as we gain more visibility to how long those patients are continuing to survive.
In terms of PFS and OS, what do we consider would be a win? I think based upon the data that we have generated today with the PFS, for example, I think you would agree that the 10 months is significantly higher than what we would have to meet for this product to be approved. And so, very similarly with the overall survival, as I mentioned, we don't have our median overall survival yet, but based upon the 12-month overall survival rates, we can identify what an appropriate hazard ratio should lead us to. And so, as we've designed the Phase 3 clinical trials, we've made sure to ensure that we
are not being overly aggressive with those endpoints.
As we design these, we also take into consideration the fact that our control arm may do better than has been reported in Keynote 048, for example. And so, all these are taken into consideration as we design those endpoints to make sure that we are not being overly aggressive in what we consider those endpoints to be, especially considering the fact that we don't believe we have to meet the goals we've achieved today with PFS and potentially overall survival to have this product approved.
Lauren V. Wood, Chief Medical Officer
There was a lot of enthusiasm and interest from ASCO attendees during the head-and-neck poster session. In her discussant review, Dr. Erminia Massarelli of the City of Hope Comprehensive Cancer Center in Los Angeles noted PDS 0101's novel mechanism of action, favorable toxicity profile, and impressive 12-month overall survival rate were absolutely in agreement with her opinion that a prospective comparative trial is needed to confirm the long-term outcomes in a larger sample size with further examination of biomarkers, as we're planning to do in Versatile 003.
As the data matures from Versatile 002, we'll also continue to examine the durability of the consistent trends that Frank has previously noted and highlighted in the clinical and safety efficacy outcomes that we've observed to date. Thank you.
Calpitt Patel - B. Riley
Hey, good morning. Thanks for taking our questions. Maybe first on the data set, from those nine confirmed responses that you have for the doublet, do we know what the CPS range was for those patients, specifically how many of those patients had high CPS, maybe greater than 20 in that update?
Frank Bedu-Addo, Chief Executive Officer
So, in the demographics, we've noted that 50 percent of the patients had CPS score greater than 20, and the other 50 percent in the MITT population had CPS score between 1 and 19. And this is very similar for what was reported in Keynote 048, where I believe about 51 to 52 percent of patients had CPS score greater than 20.
As we've analyzed our data, there is no statistically significant impact of CPS score on the results that we've seen today with PDS0101 plus Keytruder, which is what you would hope to see because PDS0101's immune response is independent of PD-L1 expression. And that appears to be what we've seen with these patients, where we are not seeing a significant impact of CPS score on the efficacy results.
Calpitt Patel - B. Riley
And then, for the Kaplan-Meier curve for the overall survival, can you talk a little bit about the censoring in that study? It looks like only four patients died and the rest were censored. So, were most of these patients lost to follow-up, or is it just an immature data set that sort of yielded these results? Any additional color would be useful here.
Frank Bedu-Addo, Chief Executive Officer
Yeah, I think the censoring may be creating a little bit of confusion, but essentially all the
patients were evaluated.
If you look at that overall survival plot, the patients involved the full ITT population of 48
patients, and we have the earlier patients, the first 14 patients who do not constitute that MITT but are part of the ITT are the patients, as I described earlier, who have had one dose but who have not yet had their first scan.
And so, when you look at these patients over here, the way this 12-month overall survival rate is calculated, the statistical weighting gives much more weight to the patients who have stayed longer on the trial and who have survived longer. And so, there's much less impact from the patients who have not stayed very long on the trial.
So, for example, if we take out those 14 patients and just concentrate on the MITT, the 12-month overall survival rate goes to 86.5%, so really not much impact of the earlier 14 patients. So, it's a pretty robust calculation based upon the statistics that are used to evaluate these patients, but all of these patients have gone through studies, and as I mentioned, we've only had four deaths on the trial, and if you look at the swimmers plot, it identifies specifically which patients have left the trial and which ones are still on the trial.
Calpitt Patel - B. Riley
And then one last question, just to be crystal clear on the unconfirmed responses. You had five unconfirmed responses, but you said two of those five have progressed and will not be confirmed as responses. Is that correct?
Frank Bedu-Addo, Chief Executive Officer
That is correct.
So, the two patients who have had the red in about 70% and 40% tumor shrinkage, those two patients, due to the fact that their tumor sizes have increased by more than 20% over the best identified response at their previous scan, based upon that, those two patients will not have a confirmed PR or CR.
One of them, for example, had a complication and had to come off the trial. And so, once the patient comes off the trial and missed their treatment, which one of those patients did, that patient then saw progression and had to leave the trial, but we still have to document that the patient who came on the trial has seen progression of their disease. And so, we capture it on that plot, just to make sure that everything is accurately captured.
So, the patient who had the 70% tumor shrinkage, for example, that patient took their dose, had to come off the trial because they couldn't take their subsequent dosing, but we still capture that in our plot.
The other three patients are still on the trial and just haven't gone through their subsequent telemetry scan yet.
Calpitt Patel - B. Riley
And could we see the data for the other three patients in the second half this year?
Frank Bedu-Addo, Chief Executive Officer
Our anticipation is that probably in the second half of this year, by the second quarter of next year, based upon the fact that we have enrolled all the patients at this time, we anticipate that the full data package or the results for the full cohort, the final results, will potentially be presented at ASCO next year.
Leland Gerschel -Oppenheimer.
Hi, good morning, Frank. Thanks for taking our questions. With respect to the PFS, I know it's early estimated based on the KM analysis of 10.4 months, obviously a pretty strong number. At the same time, there's a wide confidence interval there. If you could put sort of into context, based perhaps on other studies, how that may narrow and how medium PFS may come down, even though I know you are presuming that there will be less of a value down the road as you plan your Phase III, but how we should think about kind of the trajectory of medium PFS and the spread as data continue to mature.
Frank Bedu-Addo, Chief Executive Officer
I think what I would be very hesitant to do is to project what we are going to see based upon what other people have seen in other studies, because as you know, our mechanism of action is very different, and we've seen very differentiating data in this trial. So I think I would be very hesitant to say we're going to see XYZ because somebody else has seen XYZ with a different technology in another study.
I think what's very encouraging to us as you look at the waterfall plots and the spider plots is how long these patients are continuing to have ongoing responses. We see very few patients who, if you look at the spider plot, should start to have increase in their tumor size. And so based upon that data today, in terms of some of those patients who have even approached 600 days, I think we are very encouraged by what we are seeing over there, and I think with a trial that's continuing to enroll, we're taking data at a certain – we're taking a snapshot of the data at a specific time. And so I think once we've now enrolled all these patients, let's give it some time, let's get the data accumulated from all the patients, and at that point we can report what the final PFS and overall survival rates are.
But just based upon what we've seen, we can see that this appears to be differentiating from what has been reported in other trials. So we are highly encouraged and we are very optimistic, but just waiting to see what those final numbers will be so we can – we'll have those final numbers as we – and that should come in parallel once we've started the Phase III clinical trial, as I mentioned, by sometime the first half of next year.
Joe Pantgenis -HC Wainwright
Hey, everybody. Good morning. Thanks for the detailed update, and congrats on the data. So, Frank, obviously the – we think the pictures speak volumes, and I'd like to link the spider plot with some of your earlier comments that you touched upon with regard to mechanism of action and maybe get a little more emphasis on it as well. So this – the way we view it is that this spider plot really bawks against the conventional thinking of IO that would need to see, you know, responses evolve over much longer time periods. But the fact that you're seeing, you know, these T cells come in within 14 days and see such rapid responses, I'm just hoping you could link that a little more to the mechanism of action versus typical IO thinking.
Frank Bedu-Addo, Chief Executive Officer
Yes, I think that's something that we have really – we've analyzed and seen. So based upon the mechanism of action, one of the key things that our technology is able to do, as we've discussed before, is really recruit a large number of T cells pretty rapidly by effectively presenting these tumor-specific antigens into the right presentation and processing compartments of the immune system, but simultaneously activate the type 1 interferon signaling pathway, which is a critical immune-activating pathway for CD8 and CD4 T cells. By being able to perform this function pretty rapidly, we see that we're able to generate a pretty rapid anti-tumor response.
And actually, when we met with the FDA, Dr. Katherine Price from Mayo Clinic, she was at us at that meeting with the FDA. And one of the things she mentioned was that when she puts patients on other treatments, like checkpoint inhibitors, for example, it takes quite a while for her to even be able to determine whether or not that patient is going to be a responder. However, with the combination of PDS0101 and Keytruder, she sees those responses occur pretty rapidly. And what's also very interesting or encouraging to her was also the tolerability of the combination that the patients really like getting on this combination.
And so, based upon that mechanism of action, the two key things, one of the reasons why we give just four doses and don't have to continuously dose the patients multiple times is because of this rapid induction of the immune response. And also, very importantly, the mechanism of action leads to a memory T cell response. And so, by generating that memory T cell response with the PDS0101 monotherapy study, we saw that memory T cell response be generated by the third dose, right? And so, we give a subsequent fourth dose, but again, we don't have to continuously dose the patient. And the fifth dose on cycle 12 is really given to reboost that memory response. Just in case that memory response is waning in some patients, we could then boost that response.
So, if you look at the spider plot, that's rapid T cell induction. If T cells are being generated and T cells are actively infiltrating the patient's tumors, as we saw at SITC last year, we would expect that if those T cells are active, we should start to see rapid shrinkage of those tumors. And that's exactly what we see.
The other thing that we seem to be able to achieve here is even after inducing tumor shrinkage, we are able to induce a durable response, and we believe that's due to the fact that the patients are enerating or developing a memory T cell response. So, the body's immune system continues to recognize that foreign agent and continues to fight against that foreign agent, therefore prolonging not only the durability, but also the survival of the patient.
So, we believe this is directly linked to the mechanism by which PDS0101 is acting. And also, what's very encouraging is the fact that we're seeing this across multiple trials, right, very consistent with the cervical cancer trial where they showed those T cells actually very rapidly infiltrating the patient's tumors, and also the National Cancer Institute study where they showed that even terminally ill patients who had failed all treatment options were generating large quantities of these multifunctional HPV-specific T cells. So, again, very consistent across the trials we're running today, which is also very important when investigational immunotherapy.
Robert LaVoyer with Noble Capital Markets.
Good morning, and congratulations on the data. My question has to do with the pattern and the response that you see and whether the tumor shrinkage followed by return of growth of the tumor is something that's common that would result in a sawtooth pattern or whether it's more of a steady decline and just what the tumor is actually doing over the course of the therapy.
Frank Bedu-Addo, Chief Executive Officer
I will attempt to answer that, and I'll also let Lauren add if there's anything I missed that she would like to add.
Every patient is different. Some patients are going to generate stronger immune responses than others, and other patients' tumors are probably going to find ways to eventually start to evade immune attack. That's just the way cancer behaves. Some patients may be a lot sicker, may have much weaker immune responses than others, right?
So we see significant differences in the way these patients respond to treatment. However, what's notable here is, as we compared to the Keynote 04H studies, is the number of patients who are seeing tumor shrinkage, almost 70% of patients seeing tumor shrinkage, which suggests that a really large percentage of these patients are having clinical responses to the combination.
But in addition to that, not only the percentage of patients who are responding but how long these patients are continuing to have these clinical responses, right? And so that's something also very notable that we've seen here that we believe is differentiating.
But in terms of one of the key things we've noted also is that a patient just having progressive disease hasn't necessarily translated to the patient not surviving. If you look at our swimmers plot, there are many patients who have been identified with progressive disease but who continue to thrive and continue to do very well.
Now, one of the things that we have seen in our preclinical studies is what we call pseudo-progression, right? And so as T cells infiltrate tumors, the tumors may swell initially, but then we see a rapid decline, right? That's something that's very difficult to prove in humans, right? But the fact that patients who may see some disease progression continue to thrive and do really well tells us that the combination is actually changing the immunology of the tumors and how the tumors behave. And therefore, even if the tumor is progressing, it appears to be progressing at a much slower rate, right? And therefore, the patients continue to live much longer.
And so all these lead us to be highly encouraged about the ultimate goal that we're trying to achieve here, which is keep the patients alive, have the patients live a high-quality life, and also make it a therapy that is very well, at least well tolerated within the standards of oncology treatment, right? That's our ultimate goal.
Today, everybody thinks about improved efficacy in cancer has to come with increased toxicity. What we are showing here is that we have the potential to improve therapy and survival with a combination therapy that is actually quite well tolerated and on which the patients can live high-quality lives. I think that's what we've seen with the results that we've presented to date.
Lauren, is there anything on your end that you think I might have missed that you'd like to add?
Lauren V. Wood, Chief Medical Officer
No, Frank, I think you've covered it all. We really have not seen any had a kind of sawtooth progression, increase in shrinkage of tumor, increase in tumor, shrinkage of tumor. You've highlighted the fact that, yes, there is a great deal of variability in terms of the kinetics of tumor shrinkage among individuals based on their ability to mount an immune response, but we are seeing this consistent tumor shrinkage
that then is prolonged, and that is contributing, I believe, strongly to the overall survival trends that we're seeing.
Importantly, we do want to try and get at the issue of pseudo-progression. We know that it rarely occurs in head and neck cancer. We have had an investigator report to us one case of pseudo-progression to date, so we're continuing to monitor for that. We're also trying to explore tumor growth rate kinetics that may help us understand tumor growth rates and impacts of PD-SO101 and Keytruda combination therapy on the tumor growth rates, because if there's not only tumor shrinkage but also slowing of the ability of tumors to grow based on the tumor-specific responses that are induced by the combination, that, again, would lead to prolonged and more sustained and durable responses.
I thought the question might come up regarding the median duration of response, and for those individuals who have been responded in this data set, the median duration of response is actually not estimable, with a lower 95% confidence bound of 9.5 months and the upper confidence interval not estimable. So, again, I think the data is consistent in what we're observing in terms of PFS and overall survival and tumor shrinkage.
And just to throw back to Joe's comment about the mechanism of action, we have preliminarily confirmed in versatile 002 subjects that we see induction of HPV-16-specific CD8 and CD4 T-cell responses that are multifunctional and hope to be able to present at a scientific meeting later this year any potential correlation of those multifunctional responses with clinical outcomes.
Robert LaVoyer with Noble Capital Markets.
You just answered my follow-up question. So, the other thing I was going to ask is whether there are any updates on the triple therapy trial design. It's the last mention of it.
Frank Bedu-Addo, Chief Executive Officer
So, no, there are no updates to our triple combination study design at this time.
Kalpitt Patel - B Riley
Yeah, hey, thanks for taking the follow-up. One more question on that waterfall plot. On that footnote, it says four patients experienced unconfirmed tumor shrinkage and subsequently experienced PD. Can you point out in the plot which four patients those are? Thank you.
Frank Bedu-Addo, Chief Executive Officer
You'll notice that there are four patients below the baseline who are colored in red. Only two of them had an objective response. So, there are two who had tumor shrinkage but not an objective response.
So, those other two are not even in the discussion for confirmed or unconfirmed objective responses.
They just had some tumor shrinkage and then subsequently saw some increase in their tumors again. So, you'll see that two are below the 30% tumor shrinkage line and two are above the 30% shrinkage line. Those above the 30% shrinkage line are considered stable disease and not PR. So, those would not be involved in either a confirmed or unconfirmed objective response.
Kalpitt Patel - B Riley
So, it's the four red bars that are pointing downwards that you're referring to, correct?
Frank Bedu-Addo, Chief Executive Officer
The four red bars that are pointing downwards, exactly. Those are the four who had tumor shrinkage and then became a PD after they showed some increase in their tumor sizes. So, remember, Kalpitt, as I explained earlier, so long as you have a 20% increase over your best response, you'll be considered PD using our approach even if your tumor size is significantly lower than the 30% shrinkage. But we also have to distinguish between those who have tumor shrinkage and are stable disease versus those who have tumor shrinkage and have an objective response, which is greater than 30%. So, there's a key distinction between those two populations.
Kalpitt Patel - B Riley
Okay. Maybe we can take it offline, but I don't see the purpose of why you would include those two patients and sort of highlight them. That didn't reach 30%, but any more quality there would be useful.
Frank Bedu-Addo, Chief Executive Officer
I think we're just trying to be very transparent with everyone, right? Yes, we want to make people understand that, yes, they're still stable disease, or the other two are still stable disease and the other two have tumor shrinkage greater than 30%.
However, according to RESIST 1.1 for the best objective response that we are following, we will characterize anybody who has a tumor size increase of greater than 20% as progressive disease. And we're just trying to be extremely transparent as to how we're characterizing these patients and how they're responding.
So, to all who attended our call today, we appreciate you joining today's conference call. We are extremely pleased with the response to our data presented at ASCO this year and also our continued progress. We continue to be excited about our upcoming milestones and we look forward to continuing to update you on our progress. I wish you all a great week and thank you very much.
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