Novel Immunotherapy Combo for Lung Cancer Shows Promise in Early Trial

The therapy is a combination of a checkpoint drug, nivolumab, and a new immune stimulation drug, ALT-803.

A novel immunotherapy combination may help patients with non-small cell lung cancer who do not benefit from checkpoint therapy alone, according to a new study published in The Lancet Oncology.

Immunologist John Wrangle, MD, of the Hollings Cancer Center at the Medical University of South Carolina and colleague Mark Rubinstein, PhD, also of the Hollings Cancer Center, designed the clinical trial, which began in 2016.

The therapy is a combination of a checkpoint drug, nivolumab, and a new immune stimulation drug, ALT-803, both of which have never been combined before. According to the study, pre-clinical research shows that ALT-803 activates the immune system to mobilize lymphocytes against tumor cells and could potentially serve as an important component in combination treatments. The stimulator is a combination of an immune system growth factor for certain kinds of white blood cells, including natural killer cells and T cells, and its soluble receptor.

“What’s unique about our trial is that its 2 completely different types of drugs that have never been combined in humans before, and the trial demonstrated that these drugs can be safely administered,” Dr Rubinstein said in a press release about the study. “And also, there’s evidence that it may help patients where checkpoint therapy is not good enough alone.”

Most patients with metastatic non-small cell lung cancer are treated with immunotherapy following chemotherapy. “Checkpoint” inhibitors, a class of immunotherapeutic drugs, target checkpoints in immune system regulation to allow the body’s natural defenses to more effectively target cancer.

In the trial, 21 patients were treated at 4-dose levels of ALT-803 in combination with nivolumab. Of the 21 patients treated in the clinical trial, 9 previously either had stable disease or responded to single-agent immunotherapy before becoming resistant. Of these 9 patients, 100% either had stable disease or had a partial response to the treatment used in the study, according to the findings.

Notably, this immunotherapy combination can be administered in an outpatient setting, unlike other immunotherapies that require hospital admission.

Dr Wrangle noted that, although the results are promising, further studies are needed to evaluate the combination in a larger group of patients; however, the trial results are a step in the right direction for cancer treatment.

“Whereas for decades the modalities of therapy were surgery, radiation, and chemotherapy, the last decade has brought targeted therapy and more recently, immunotherapy,” Dr Wrangle said in the press release. “It fundamentally alters the balance of power between your body and your cancer.”

References

Wrangle JM, Vamsidhar V, Patel MR, et al. ALT-803, an IL-15 superagonist, in combination with nivolumab in patients with metastatic non-small cell lung cancer: a non-randomised, open-label, phase 1b trial. The Lancet Oncology. 2018. Doi: https://doi.org/10.1016/S1470-2045(18)30148-7

New immunotherapy for lung cancer shows promise of success [news release]. MUSC’s website. http://academicdepartments.musc.edu/newscenter/2018/hcc-lancet-study/index.html. Accessed April 6, 2018.