Results from a recent clinical trial to treat lung cancer show that a novel immunotherapy combination is surprisingly effective at controlling the disease's progression. The study, published April 4 in the journal The Lancet Oncology, focused on non-small cell lung cancer, which is the most common form of lung cancer.
The results are from a clinical trial that began in 2016. The trial studied the combination of a checkpoint drug, nivolumab, with a new and powerful immune stimulation drug, ALT-803 in patients with pretreated, advanced, or metastatic non-small cell lung cancer.
Patients with metastatic non-small cell lung cancer will always progress after chemotherapy, so most patients go on to be treated with immunotherapy, a type of therapy that uses the body's immune system to fight cancer. One class of immunotherapeutic drugs is known as "checkpoint" inhibitors, as they target checkpoints in immune system regulation to allow the body's natural defenses, such as white blood cells, to more effectively target the cancer.
Immunologist John Wrangle, M.D., of the Hollings Cancer Center at the Medical University of South Carolina said it's a promising therapy that can be delivered in an outpatient setting. "People don't talk about 'curing' patients with metastatic lung cancer. We now get to flirt with the idea for certain patients using immunotherapy. And at the very least we have a significant proportion of patients enjoying prolonged survival even if we can't call them 'cured'," he said.
Mark Rubinstein, Ph.D, who co-designed the study with Wrangle said, "What's unique about our trial is that it's two completely different types of drugs that have never been combined in humans before, and the trial demonstrated that these drugs can be safely administered, and also, there's evidence that it may help patients where checkpoint therapy is not good enough alone.”
Checkpoint drugs (or checkpoint inhibitors) target checkpoints in immune system regulation to allow the body's natural defenses, such as white blood cells, to more effectively target the cancer. ALT-103 is an immune stimulation drug that activates the immune system to mobilize lymphocytes against tumor cells. It is an interleukin-15 complex consisting of IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. ALT-803 has improved pharmacokinetic properties, longer persistence in lymphoid tissues and enhanced anti-tumor activity compared to native, non-complexed IL-15.
Patients who have stopped responding to checkpoint therapy may be helped significantly by adding ALT-803. Pre-clinical studies have shown that ALT-803 activates the immune system to mobilize lymphocytes against tumor cells and could potentially serve as an important component in combination treatments. Of the 21 patients treated, nine previously either had stable disease or responded to single-agent immunotherapy before becoming resistant to this treatment. Of these nine patients, 100 percent either had stable disease or had a partial response to the treatment used in this study.
ALT-803 is being developed by Altor Bioscience. It is currently being studied in eight clinical trials including one for HIV patients.
Nivolumab, trade name, Opdivo is owned by Bristol-Myers Squibb.