Nektar Therapeutics is launching a first-in-human Phase 1 clinical trial assessing the safety and efficacy of its investigational agent NKTR-255 in people with relapsed or refractory non-Hodgkin’s lymphoma and multiple myeloma.
The study (NCT04136756) is recruiting up to 82 patients across multiple U.S. sites and also will test a combination of NKTR-255 and Darzalex (daratumumab) in heavily-treated multiple myeloma patients.
Natural killer (NK) cells are key players in the fight against tumors but their insufficient numbers and short lifespan have limited their applicability as a treatment against cancer.
NKTR-255 is an activator of the interleukin-15 (IL-15) receptor, which promotes the survival and expansion of NK cells and other tumor-killing T-cells, without increasing the numbers or activity of immunosuppressive cells.
The investigational therapy also promotes the formation of long-term immune memory, which may lead to a sustained immune response against cancer cells.
Compared with recombinant IL-15 injections, NKTR-255 — given intravenously, or through the vein — may bring some advantages. In particular, it takes longer to be cleared from the body, which allows for less frequent administration, more convenience, and fewer toxicities.
In previous preclinical studies, NKTR-255 displayed anti-tumor activity and increased the proliferation and activation of NK cells resulting in sustained anti-tumor activity. It also improved the clearance of tumor cells flagged by an anti-cancer antibody — a mechanism that relies on NK cell activity — in an animal model of lymphoma.
The ongoing, open-label Phase 1 trial will include a dose-escalation and a dose-expansion part. First, researchers will include 40 lymphoma and myeloma patients and give them escalating doses of NKTR-255 once every three weeks to determine the optimal dose for additional studies.
Then, the dose expansion phase will include two separate groups of people. In one group, participants will receive NKTR-255 alone to continue studying its safety and efficacy. The researchers note that these patients may have received prior CAR T-cell therapies for their disease. The second group will include myeloma patients who received at least three prior lines of therapy. These participants will be given NKTR-255 in combination with the anti-CD38 antibody Darzalex.
In addition to safety — the primary outcome — the trial also will assess efficacy, tumor biomarkers, and the behavior of NKTR-255 inside the body. Specifically, the trial will examine the medication’s absorption, distribution, metabolism, and excretion.
“We are excited to launch the first-in-human clinical study of NKTR-255, which has shown promising and substantial anti-tumor activity in our preclinical studies,” Wei Lin, Nektar’s senior vice president and head of development, said in a press release.
“By increasing the number and activity of NK cells, NKTR-255 has the potential to enhance the host’s tumor-fighting response, both as a single agent and in combination with tumor-targeting antibodies, including daratumumab and rituximab,” Lin added.