So today, this one discussion is going to be different because your job and my job is going to be at stake as an oncologist if the upcoming predictions in this conversation come true. And to be honest, we would all love that. Can we really cure cancer? Hello and welcome back to the Oncology Brothers podcast. I'm Rahul Gossain, a practicing community medical oncologist here with my brother and co-host Rohit Gossain. As always with these discussions, our mission is to bridge the gap between academic research and community practice where majority of our cancer patients are getting treatment today.
That's right, Rahul. We have been talking about cancer treatment conversations around microbiome and immune modulation. Even going back, that is before immune checkpoint inhibitor, we were using IL2 treatment to excite immune system to recognize cancer cells. Today we're talking about immune restoration strategy focus on Anktiva, an IL-15 receptor superagonist to unpack what we have at hand. We're excited to welcome a true pioneer in the field of oncology, Dr. Patrick Soon-Shiong. A transplant surgeon by training, importantly he helped change the field of cancer about 20 years ago, that is bringing nab-paclitaxel which we still use in our clinic routinely for lung, pancreatic, and breast cancers. Patrick, thanks so much for joining us.
Patrick, welcome. As Rohit mentioned, your work led to the approval of nab-paclitaxel, Abraxane, back in 2005. And more than 20 years later, we're still using this heavily in our clinical practice. But now, your work has been around IL-15 receptor agonist with hope to cure cancer. This is currently approved in non-muscle invasive bladder cancer here in the US and more recently this received an accelerated approval in Saudi Arabia for non-small cell lung cancer with immunotherapy. Can you touch a little more on the mechanism of action for Anktiva? You know, as medical oncologists, we feel very comfortable with PD-1, PD-L1, and CTLA-4 blockade. But what's the biology around IL-15?
Well, thank you for having me. So, look, I love the idea that I'm talking to community oncologists. That's where actually all the patients are. That's how we treat patients where we can treat them as outpatients. And your patients are your patients for life. They trust you. They're there locally. And by the way, I heard your opening. This is not to replace the community oncologist. In fact, not to enhance it. So, let me give you a little bit of sad sort of scientific error, so to speak. You spoke about IL-2 and you spoke about IL-15. As you know, IL-2 got accepted, approved way, way, way back for renal cell carcinoma. Sadly the mistake, and this is where the mistake was in the scientific understanding and we've only learned of this mistake now, is IL-2 and IL-15, which is these two cytokines in your body, so they're natural products in your body, stimulate the same receptor on the T-cells and NK cells. So if you use IL-2, when it goes onto the T-cells, guess what happens? It stimulates the suppressor cells. It actually went the wrong way and that's why it was not only toxic, it didn't work. On the other hand, when you stimulate IL-15 on your T-cell, it proliferates the T-cells and makes them a killer T-cell. So in 2012, the NIH/NCI wrote a paper that the most important cytokine or interleukin in the history of medicine that could cure cancer was IL-15. So why was it never approved or developed? Well, they tried. The NIH tried, NCI tried because when they injected it, it lasted for a few minutes, it was gone. So we modified this IL-15 so that it has a long acting and it's a subcutaneous injection. That's it. A subcutaneous outpatient injection to allow your body to be the factory. And this lasts so that your T-cells grow, your NK cells grow, your memory T-cells grow and now you have your killer cells around your tumor independent of the tumor type. That was a revelation that I said wow, it's not what I call the cure of cancer. This is the foundation of how we can attack cancer and address it. What was really disturbing to me, and I trained under Don Morton in melanoma at UCLA and the cancer center. I did all the Whipples and then I would follow the patients when the oncologist would treat them. As soon as you give chemotherapy, you should ask your colleagues. You all look at the CBC and you look at hemoglobin, you look for anemia and you give epoetin, you look at the ANC and you give Neupogen and you give Neulasta so you can give more chemo. Right? It turns out that both chemo and radiation knocks out your NK cells and your T-cells. Do you need your NK cells and T-cells to kill cancer? And the answer to that is yes. I mean, we all of us never been taught to look at ALC, not ANC, but ALC. And the reason for that is there's never been a treatment ever in the history of medicine to stimulate your NK cells with a single injection and increase your ALC. We have now found that if your ALC is below 1,000, you're in real trouble. If we get your ALC above 1,000 to 1,200, we triple the median overall survival of lung cancer. We've done a randomized clinical trial to show that in lung cancer against checkpoint inhibitor versus checkpoint plus Anktiva, the ALC goes up, checkpoint goes down. If you get chemo radiation, you should look at your patients that you sent to radiation, look at the ALC two weeks, three weeks after. I would guarantee you 90% ALC will be dropped below 1,000. So this is what happens where for the first time we have in our armamentarium ability to give a patient an outpatient injection and stimulate the ALC and once you do that all of a sudden patients that were in progression turn around. So we are now seeing complete responses in glioblastoma, recurrent glioblastoma. We're seeing patients with triple negative breast cancer, lung cancer, prostate cancer. And the answer is why? Because it's universal. So this is one of the first universal truths is that we have in our body the power within us to stimulate the very cells that kill cancer with a simple subcutaneous injection that's already approved but a tiny subset of bladder cancer.
Well, thank you so much Patrick to cover that important mechanism of action that is trying to expand and activate the natural killer cells or NK cells to restore anti-tumor immunity. Well, as you mentioned, multiple studies around Anktiva have shown that what we are trying to do is improve that lymphocyte count. From US standpoint, we have this approved in bladder space.
So if you go to clinicaltrials.gov and type in the word QUILT, I made up that word. It meant Quantitative Integrative Lifelong Trial. We've done that in triple negative breast cancer, pancreatic cancer, head and neck cancer, Hodgkin's lymphoma, published, and you're seeing this universal increase in survival. So let's talk about even lung cancer. We did a randomized clinical trial in first-line lung cancer, showed specifically statistically significant increased ALC when we compared the checkpoint inhibitor alone versus checkpoint inhibitor plus Anktiva. We then did a single arm trial in patients who failed chemo radiation, progressing on checkpoint, second-line lung cancer, where the current standard in your practice would be docetaxel, median survival 7 to 9 months. Every trial that's been done, the pragmatic trial showed that no matter what we do it's 7 to 9 months. When we take these patients, we raise ALC to 1,200 in about 78% of patients. We're now seeing median survival of 25 months in these same patients. So yes, it's applicable. And then we did that same trial called QUILT 3.055, 10 different tumor types, exactly the same thing with the hazard ratios of 0.3 and 0.4, highly significant, highly statistically significant. And we submitted this now for publication in one of the peer reviews. It gets more exciting than that because if we can use your body as the factory to make NK cells, imagine then if we give you an injection of Anktiva and then 3 to 4 days later we do what we call an apheresis. We've now invented the way of taking that leukapheresis, deconstructing that into NK cells, INKT cells and T-cells and grow them in the billions, freeze them down and give them as a product, as an outpatient hang to any patient. These NK cells are allogeneic. They're in clinical trials right now. We call them MSANK which is Memory Cytokine-Enhanced NK cells. And my goal is when you combine these two, you literally will have the World Bank of Natural Killer Cells for all community oncologists to hang as outpatients in their clinic.
You know, we keep talking about community oncology and this being outpatient because that is the big need. Our patients want to stay closer to home. And coming back to the results from the QUILT trial, these results are exciting and we should not sit on something that is active and not get this to our patients right away, but we also have to be cautious in ensuring we're not providing false hope and that is where large phase three trials come in place today. Where do we stand for Anktiva in terms of clinical trials and how close are we of this becoming a reality for patients? Again, what data do we have in today for larger studies?
