The following article features coverage from the Society of Immunotherapy of Cancer (SITC) 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

NIZ985 demonstrated antitumor activity in combination with spartalizumab with a tolerable safety profile among patients with advanced solid tumors, according to the results of a phase 1/1b trial presented at the virtual Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020).

NIZ985 is a subcutaneous treatment comprising a heterodimer of interleukin (IL)-15 and IL-15Rα, which inhibits tumor growth in animal models by promoting tumor infiltration of CD8-positive T-cell and natural killer cells.

The open-label phase 1/1b dose-escalation and expansion study included 83 patients. Patients in the dose-escalation portion (47 individuals) received increasing doses of NIZ985 as a monotherapy or in combination with spartalizumab. The 1 μg/kg dose of NIZ985 plus the 400 mg dose of spartalizumab were selected for the dose-expansion portion (36 individuals).

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The primary endpoint was safety and tolerability, maximum tolerated dose (MTD), and recommended dose for expansion. Secondary endpoints included antitumor activity, pharmacokinetics (PK), and pharmacodynamics.

At baseline, the majority of patients had received at least 3 prior lines of therapy (70%), followed by 2 prior lines (16%), and 1 prior line (6%). Prior exposure to an immune checkpoint inhibitor (ICI) was present in 50% of patients.

There were no dose-limiting toxicities. The most common treatment-related adverse events (TRAEs) included injection site reactions, chills, fatigue, pyrexia, nausea, and arthralgia with the NIZ985 monotherapy. For the combination regimen, the most common TRAEs were injection site reaction, fatigue, flu-like symptoms, and myalgia.

Serious adverse events (SAEs) developed in 6 patients, which were considered to be related to the treatment.

The objective response rate (ORR) and disease control rate (DCR) was 0% and 30%, respectively, with NIZ985 monotherapy, and 5% and 32%, respectively, with NIZ985 plus spartalizumab.

John A. Thompson, MD, of the University of Washington Seattle Cancer Care in Seattle, and presenter of the study, said that “NIZ985 displays approximately dose-proportional, time-dependent [pharmacokinetics], and a cytokine and proliferating lymphocyte response profile consistent with target engagement.”

Dr Thompson concluded that “antitumor activity was limited for NIZ985 as a single agent; however, preliminary responses were observed for combination treatment with spartalizumab … warranting further investigation.”

Disclosures: The study summarized in this article was sponsored by Novartis. The University of Washington receives funding from Novartis, Pfizer, Trillium, Xencor, and Merck to fund research by Dr Thompson.

Read more of Cancer Therapy Advisor‘s coverage of the SITC 2020 meeting by visiting the conference page.


Leidner R, Wang-Gillam A, Gupta S, et al. Phase I/Ib first-in-human study of NIZ985 (HetIL-15; IL-15/IL-15Rα) alone and in combination with spartalizumab, in adults with advanced and metastatic solid tumors. Presented at: Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020); November 11-14, 2020. Abstract 386. J Immunother Cancer. 2020;8(Suppl 3):A656–A959.