Phase I Trial of ALT-803, a Novel Recombinant Interleukin-15 Complex, in Patients with Advanced Solid Tumors.

Publication Type:

Journal Article


Clinical cancer research : an official journal of the American Association for Cancer Research (2018)


Flow Cytometry Core Facility


BACKGROUND: IL-15 induces the activation and proliferation of NK and memory CD8+ T cells and has preclinical antitumor activity. Given the superior activity and favorable kinetics of ALT-803 (IL-15N72D:IL-15RαSu/IgG1 Fc complex) over recombinant human IL-15 (rhIL-15) in animal models, we performed this first-in-human Phase I trial of ALT-803 in patients with advanced solid tumors. METHODS: Patients with incurable advanced melanoma, renal cell, non-small cell lung, and head and neck cancer were treated with ALT-803 0.3-6 mg/kg weekly i.v. or 6-20 mg/kg weekly s.c. for 4 consecutive weeks, every 6 weeks. Immune correlates included pharmacokinetics, immunogenicity, lymphocyte expansion and function. Clinical endpoints were toxicity and antitumor activity. RESULTS: Twenty-four patients were enrolled; eleven received i.v. and 13 received s.c. ALT-803. Of these patients, 9 had melanoma, 6 renal, 3 head and neck, and 6 lung cancer. Although total lymphocyte and CD8+ T cell expansion were modest, NK cell numbers rose significantly. Neither anti-ALT-803 antibodies nor clinical activity were observed. Overall, ALT-803 was well-tolerated, with adverse effects including fatigue and nausea most commonly with i.v. administration, while painful injection site wheal was reported most commonly with s.c. ALT-803. CONCLUSIONS: Subcutaneous ALT-803 produced the expected NK cell expansion and was well-tolerated with minimal cytokine toxicities and a strong local inflammatory reaction at injection sites in advanced cancer patients. These data, together with compelling evidence of synergy in preclinical and clinical studies, provide the rationale for combining ALT-803 with other anti-cancer agents.