NKTR-214 & Nivolumab: Synergistic Activity Across Tumor Types - Episode 1
Adi Diab, MD:Immunotherapy is not a new treatment for oncology; it’s one of the oldest treatment modalities for oncology. It started over 100 years with using bacteria and toxins in sarcoma patients, and then it was noticed that the immune system can shrink the tumors.
But the real breakthrough came only after 100 years, what we know right now as immuno-oncology, and when anti-agents of antiCTLA4 was proven for the first time to demonstrate an overall survival benefit. And that was a different thinking of understanding the immune system. For the first time, we understand that we do not necessarily need to stimulate the immune system, but we need to prevent the natural inhibition of the body against the immune system. And that has been a breakthrough for immunotherapy. It started with CTLA4 blockade and then it continued with a PD-1 blockade or PD-L1 blockade for the same sake.
These were the breakthroughs that were translated into clinical benefits, into clinical trials demonstrating the advantage of survival benefits. It started with melanoma and then across other solid tumors and even with lymphoma.
The battle with cancer and the immune system, we can say the cancer is still winning. Cancer kills more than 500,000 Americans every year. However, we see a shift in the tide with the immune system and immunotherapy now improving and developing into multiple regimens, and we can see the survival benefit. The advantage of immunotherapy is that what it offers is durable responses. And you can tell patients sometimes that instead of they have a terminal disease, now they have a disease that is potentially curable. That is a real relief for the patients and for the oncologists who were not able to do that.
Cytokine therapy is an old therapy; it’s not a new therapy. It has been in practice over 4 decades. And cytokines are known to stimulate the immune system and lead to proliferation of certain immune cells, including T cells, both CD4 and CD8 T cells, as well as natural killers. And those all play a part into the fight against cancer. However, the problem was with high-dose IL-2. It’s the toxicity associated with this regimen. This regimen leads to very rapid and overactive immune stimulation and inflammation in the body, and that is associated with severe toxicity, allowing the patient to be only treated in certain settings. And selective patients only can tolerate this treatment. So, it could not be applied for all patients, and it was not tested properly in the clinical trials for so many patients to really tease out how much beneficial this drug is. This drug was only approved for metastatic melanoma and renal cell carcinoma. But for years and years, and even in the current era of immunotherapy, we understand that cytokines are overlapping immune stimulators differently from checkpoint inhibitors, differently from antiCTLA4, and differently from anti–PD-1. And we try to incorporate them in a safe way into a regimen of immune therapy that can further push and improve the efficacy of these agents.
Transcript edited for clarity.