Immune Stimulant in Combination With Nivolumab for Metastatic Lung Cancer
Posted: Monday, June 18, 2018
Metastatic non–small cell lung cancer (NSCLC) often fails to respond to immunotherapy using checkpoint inhibitors. According to a new study, using the immune stimulant ALT-803 (an interleukin-2 [IL-2] or IL-15Rbg agonist cytokine) to boost treatment with the checkpoint inhibitor nivolumab appears to be safe and tolerable. The findings, which suggest a possible role for a new class of agents in this patient population, were published in The Lancet Oncology by John Wrangle, MD, and Mark P. Rubinstein, PhD, of the Hollings Cancer Center at the Medical University of South Carolina, Charleston, and colleagues.
“There’s evidence that it may help patients where checkpoint therapy is not good enough alone,” Dr. Rubinstein said in a Medical University of South Carolina press release. “We need to treat a few hundred patients in order to get a better sense of how to refine the synergy of these two classes of drugs,” added Dr. Wrangle.
The nonrandomized, open-label phase Ib trial treated 21 patients. All had previously treated, histologically or cytologically confirmed stage IIIB or IV NSCLC. They received ALT-803 subcutaneously once per week for 5 weeks, followed by 1 week off, for four 6-week cycles. The trial tested four escalating doses of ALT-803: 6, 10, 15, and 20 μg/kg. Patients also received nivolumab intravenously every 2 weeks.
The investigators recommend a safe and tolerable phase II dosage of 20 μg/kg of ALT-803 once per week, with nivolumab every 2 weeks. There were no dose-limiting toxicities, and the study did not reach the maximum tolerated dose. Two patients displayed adverse effects of lymphocytopenia and fatigue. The most severe adverse effect was a grade 3 myocardial infarction in one patient.