IL-15 Superagonist Plus Nivolumab in Advanced NSCLC
In a phase Ib trial reported in The Lancet Oncology, Wrangle et al found evidence of activity of the combination of nivolumab (Opdivo) and the interleukin (IL)-15 superagonist ALT-803 in patients with previously treated advanced non–small cell lung cancer (NSCLC). ALT-803 targets the shared IL-2 and IL-15Rβγ pathway, resulting in augmented lymphocyte response; such agents have been found to induce complete and durable responses in some cancers.
Study Details
In the study, 21 patients with previously treated stage IIIB or IV NSCLC from 3 U.S. sites were enrolled between January 2016 and June 2017. They were treated with nivolumab initially at 3 mg/kg and subsequently (upon FDA approval) at 240 mg every 2 weeks (either as new treatment or continued treatment at disease progression) plus ALT-803 subcutaneously once per week on weeks 1 to 5 of four 6-week cycles for 6 months. ALT-803 was given at 1 of 4 escalating dose levels of 6, 10, 15, or 20 μg/kg. Phase II enrolment of patients is ongoing.
Toxicities
No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached. The most common adverse events were injection-site reaction (90% of patients) and flu-like symptoms (71%). The most common grade 3 adverse events were lymphocytopenia (10%) and fatigue (10%). One patient had grade 3 myocardial infarction. No grade 4 or 5 adverse events were observed. The recommended phase II dose of ALT-803 is 20 μg/kg once per week in combination with nivolumab 240 mg every 2 weeks.
Responses
Objective response was observed in 6 patients (29%). Nine (43%) had a decrease in target lesion size, and disease control was observed in 16 (76%). Median progression-free survival was 9.4 months. Median overall survival was 17.4 months.
The investigators concluded, “ALT-803 in combination with nivolumab can be safely administered in an outpatient setting. The promising clinical activity observed with the addition of ALT-803 to the regimen of patients with programmed cell death protein 1 (PD-1) monoclonal antibody relapsed and refractory disease shows evidence of antitumour activity for a new class of agents in NSCLC.”
The study was supported by Altor BioScience (a NantWorks company), National Institutes of Health, and Medical University of South Carolina Hollings Cancer Center.
Mark P. Rubinstein, PhD, of the Departments of Surgery and Microbiology and Immunology, Medical University of South Carolina, Charleston, is the corresponding author of The Lancet Oncology article.
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