NantKwest Inc. announced the launch of a novel triple combination, phase II clinical trial in Merkel cell carcinoma (MCC). NantKwest’s phase II immunotherapy trial builds upon the company’s earlier phase II single-combination study using its proprietary, off-the-shelf aNKTM natural killer cell therapy and IL-15/Fc superagonist (N-803), which produced an objective responses in 3 of 7 patients. In this new clinical trial, patients will be dosed with: the novel chemotherapy-free combination of haNK cell therapy, which are aNK cells that are genetically engineered to express the high-affinity variant of the CD16 receptor (V158 Fc?RIIIa), avelumab, a PD-L1 targeting checkpoint inhibitor, and N-803, a superagonist IL-15/Fc cytokine therapy, in a regimen designed to synergistically optimize the therapeutic potential of each agent. In preclinical and human clinical studies conducted by NantKwest, the combination of haNK cells with a number of different therapeutic antibodies, including avelumab, led to enhanced tumor cell killing when compared to the use of the antibody alone. The IL-15/Fc superagonist N-803, developed by NantCell, Inc., an affiliate company, has been shown to synergistically activate NK and T cells and enhance cancer cell killing in both single agent and combination therapy. The PD-L1 checkpoint inhibitor avelumab, a monoclonal antibody developed by Merck KGaA and approved in 2017 by the FDA, targets the programmed death-ligand 1 protein (PD-L1), commonly expressed on a wide range of cancer cells. Avelumab works by blocking PD-L1 from binding PD-1 receptors on T-cells, resulting in an increase in CD8+ T-cell immune responses. This effect is amplified with the addition of N-803 and haNK cells. With encouraging preclinical and clinical responses already demonstrated for aNK as a single agent therapy or in combination, the company believe this existing dataset provides validation for novel, triple combination clinical trial design. MCC is a rare and aggressive skin cancer that arises from uncontrolled growth of cells in the skin. Increasing in incidence, approximately 2,500 new cases are reported in the U.S. each year. Patients with metastatic or locally advanced MCC have an extremely poor prognosis, with less than 20% of patients surviving longer than five years. Typically these patients are treated with a range of drugs, including chemotherapy, which can result in significant side effects. Although new immune therapies have the potential to improve survival, MCC is still fatal for a majority patients who have progressed on or after treatment with a checkpoint inhibitor and represents an unmet medical need. The Phase II clinical study will evaluate a combination therapy with off-the-shelf CD16-targeted natural killer cells (haNK), the IL-15 superagonist (N-803), and avelumab, without the use of cytotoxic chemotherapy, in subjects with MCC that have progressed on or after treatment with a checkpoint inhibitor. The combination of these agents have been safely studied in previous clinical trials for other solid cancer indications. The goal of combining these therapies is to synergistically maximize the killing of cancer cells while attempting to spare patients from chemotherapy and its associated adverse side effects.