I think the field of cancer and in particular, head neck cancer has been. Somewhat revolutionized with the introduction of immunotherapy. We now use single agent TD1 therapies first line with KEYTRUDA® (pembrolizumab).
However, responses or activity is modest. We only have a response rate to about 16 to 18% with single agent pembrolizumab and the big unmet need in the field is what can we do better? How can we improve? What is arguably a dramatic impact on survival, long term survival in a very tolerable treatment.
So, there is just an announcement about a new study coming from Nektar. They have a medication called Bempegaldesleukin or short, BEMPEG or also called NKTR-214 . What is called PEGylated IL-2 is a very old drug. It's arguably the first immunotherapy we had.
Interleukin-2 has these classic characteristics of immunotherapy with long term overall survival in a fraction of patients. However, it was very toxic. And so it's still used occasionally with proleukin interleukin-2 high dose for melanoma and for kidney cancer. The problem is people get very sick from hypertension vascular leak syndrome.
And it has to be done in an ICU or ICU like setting. And so, it's not feasible to be used broadly NKTR-214, or Bempegaldesleukin (BEMPEG)) . Take the inter look in two and paste it. And so, it leads to two different characteristics. One being it is long acting. And two it is what they call CD-122 bias, meaning some of the unpleasant side effects from.
Into interleukin-2 goes away because it only, or primarily preferentially activates effector cells, CD8 effector cells in case cells and CD4 helper cells, but it does not lead to the vascular leak. And it does not have the effect on TRES and so long story short, and we can go more into the mechanism.
It's a promising agent because we know that interleukin-2 is active. In fact, there's all studies of interleukin-2 and neck cancer with the injected peritumoral or in the metastatic setting. There is single agent activity for interleukin-2 in other cancer types. But now you have this new agent that is more favorable and the study is very simple.
The study is KEYTRUDA® (pembrolizumab) and anti-PD1 agent in the first line setting versus the combination. Bempegaldesleukin (BEMPEG) plus KEYTRUDA® (pembrolizumab). So, we are testing the addition of Bempegaldesleukin (BEMPEG) or NKTR-214 in addition to KEYTRUDA® (pembrolizumab). So that's the brief outline this is a large randomized. Phase 2/ 3 study.
It's really meant as a phase three study, but there will be an interim look at the data first. And this has potential to change the standard of care first line, if it turns out to be positive obviously we don't know how it will turn out, but it's exciting to have a combination being tested to potentially, know, improve upon NTPD1 activity.
And it's not chemotherapy. It is actually, mechanistically very well aligned with checkpoint inhibitors. It is immunotherapy.
What are the most common questions? I think there's a lot of data with interleukin two in good and bad ways. As I mentioned, it has activity in melanoma and renal cell cancers, FDA approved. So is Bempegaldesleukin (BEMPEG). Different from regular interleukin-2. I think the two characteristics, as I mentioned before, is that it's peated, it's long acting.
So, you don't have to give it as a continuous infusion. You can do it in the outpatient setting. So, it's a lot more convenient. You don't need an ICU admission or inpatient state, and the side effects are much better. So, what are the side effects? The side effects are still related to the mechanism of two.
But they're much, much more tolerable. So, the most common side effects are flu-like symptoms and a rash. So, they are classic immunotherapy side effects skin itching. So, they're typical for what we want the immune system to do. But they're no longer the vascular leak.
They're no longer patients becoming severely hypertensive that have gone away. So, it becomes much, much more feasible as an outpatient medication. And also, you give it at a regular interval rather than having to do a continuous infusion with what's high. That's the first question, how is it given?
And the side effects are much better. The discontinuation rate is very low compared to the major side effects regularly to look into, so that's question one, question two. What's the data so far? Why is this so exciting? Why do you care about this in head and neck cancer?
And so, I would say one is, we know in, in melanoma the combination of MPA and nivolumab has received FDA breakthrough designation. They have a response rate of, I believe, 53% and a high. CR rate of 34%. I should probably crosscheck those numbers, but that's really good. If you treat melanomas I think you get, you realize that especially the CR rate is.
Is remarkable. And we know that deep responses or complete responses are those responses at last. And so, if you think about long term survival, the deeper, the response and those analyses have been done in multiple tumor types, deep responses are meaningful because they correlate with long term survival.
So, I think that's exciting data. There's also exciting data in lung cancer and actually Bristol Myers is running phase 3 studies in several indications with nivolumab plus. The other part, the side effects, activities so far, I should point out that this study is using KEYTRUDA® (pembrolizumab) as KEYTRUDA® (pembrolizumab) is a standard of care.
So, this is a collaboration of Nektar with Merck. And so, this is now KEYTRUDA® (pembrolizumab) another PD1, they are actually data of KEYTRUDA® (pembrolizumab) also with Bempegaldesleukin (BEMPEG). That's a phase two study again in lung cancer. This is now a study applying this to another disease where there is, good preliminary data from, old data with interleukin-2 of looking at the L2 mechanism.
What other questions mechanistically do you know why does this make sense? Why would you do this? There is very nice translational data already, and they suggest that interleukin-2 in particular, Bempegaldesleukin (BEMPEG) does two things that we care about. It leads to a marked increase in proliferation of T cells. So CD8 cells and NK cells, T-effector cells essentially. While it does not have as strong of an effect on the immunosuppressive cells like T regulatory cells. So that's very positive. The other thing that's very intriguing is in tissue samples pre and on treatment, it does appear that PD1 negative patients or tumors can turn PD1 positive.
So, IL2 is essentially, as you pour into the inflammation or the fire to lead to PDL1 expression, is that really going to happen every single time? I don't know, but the early data suggests that I L two is a very effective mediator of increased PDL1 expression. So especially, if you have tumors that may not be high on PDL1, or even PDL1 negative This may be something that helps actually increase the ability of then the checkpoint in which work.
So, the translational data is very much aligned with what we want to see. And if you look at inflammation signatures there's a gamut adhere signature. This has been worked on actually by a number of researchers at Merck and other companies. They suggest that these gamut signatures predict benefit.
IL2 is a very effective medium. So, the mechanism makes a lot of sense. It's very much aligned. It's what we want to do with immunotherapy. Other than that, I think those are probably the three biggest questions that people ask me. So, why, what is the data so far? And then the side effects.
I mean as with every study, you have to wait for the outcome to know if it really will affect patients. The potential is very significant. So, Bempegaldesleukin (BEMPEG) will. Is in phase three testing in melanoma that could read out soon. I don't know the details, but I believe that could change practice for melanoma, for head and neck cancer.
I do believe that KEYTRUDA® (pembrolizumab) alone is a dramatic treatment, but the response rate only on the order of 16 to 18%, there's a lot of room for improvement. I'm very hopeful that this will change the standard of care in the first line. If the study is positive, I think it's a very valuable study because this would be an improvement upon KEYTRUDA® (pembrolizumab) alone.
So, I'm very hopeful that this is a study that might change this standard of care. Again, we'll have to. We'll have to wait until the study enrolls and reads.
The study is just launching. So, I think the next step is to enroll in the study. Maybe get biomarker data. The other part is we can certainly look forward to the other cancer types, melanoma, lung cancer, bladder cancer, to see activity of Bempegaldesleukin (BEMPEG) in those diseases. I think oftentimes, immunotherapies have efficacy across indications.
So, I believe that. These other cancer types that are further along will provide us some good guidance. Again, I believe the early data are quite exciting. These are non-randomized studies, but the randomized data in these other tumor types we will know soon and again I am optimistic that once that's the case, we will have a lot of momentum for this study for head and neck cancer as,
I think IL2 is a tried and true. However, quite toxic effective immunotherapy. We know that IL2 works Bempegaldesleukin (BEMPEG) or NKTR-214, or Bempegaldesleukin (BEMPEG) is a new version of, IL2 that's long acting that avoids the side effects of IL2 but has all the right characteristics of increasing PDL1 leading to massive T-cell proliferation.
And again, the early data in melanoma and lung cancer are quite exciting. So, what I would like to say as a closing statement, this is exciting to see another. Immunotherapy moves forward. The combination with KEYTRUDA® (pembrolizumab), I had neck cancer makes a lot of sense and I have another treatment that's promising that may actually change or improve on what we already have with NTP1 agents.
Tanguy Seiwert, MD, Director, Head and Neck Cancer Oncology Disease Group, Co-Director Bloomberg~Kimmel Institute for Immunotherapy/HNC Program, Assistant Professor of Oncology, Assistant Professor of Otolaryngology-Head and Neck Surgery at Johns Hopkins University, speaks about the Nektar Announces Agreement for Phase 2/3 Study of IL-2 Pathway Agonist, Bempegaldesleukin, in Combination with Merck's KEYTRUDA® (pembrolizumab) in Patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN).
Nektar Therapeutics announced today that it has entered into a clinical trial collaboration and supply agreement with Merck (known as MSD outside the US and Canada) for a Phase 2/3 study of bempegaldesleukin (NKTR-214, BEMPEG), Nektar's investigational IL-2 pathway agent, in combination with Merck's KEYTRUDA® (pembrolizumab) for first-line treatment of patients with metastatic or unreselective cancer The research will begin in the second half of 2021.
The Phase 2/3 trial, which is planned to enroll 500 patients with metastatic or recurrent SCCHN with PD-L1 expressing tumors, will be conducted by Nektar under the terms of the agreement. Patients would be randomly assigned to receive either BEMPEG plus pembrolizumab or only pembrolizumab. After the first 200 patients enrolled have had a minimum of four months of follow-up, the Phase 2 section of the study will include an interim review of overall response rate (ORR). The research will resume if the ORR exceeds a predetermined futility boundary, and the remaining 300 patients will be enrolled in the Phase 3 portion of the study. ORR and overall survival (OS) are the trial's primary endpoints; progression free survival (PFS) is a secondary endpoint.