Nektar Therapeutics is launching a first-in-human Phase 1 clinical trial to assess the safety and efficacy of NKTR-255 in adults with relapsed or refractory multiple myeloma and non-Hodgkin’s lymphoma.
“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, MD, the company’s senior vice president and head of development, said in a press release.
People with cancer have reduced amounts of natural killer (NK) cells, a type of immune cell that recognizes and attacks cancer cells. NK cells are also needed for targeted therapies — which specifically recognize cancer cells and trigger an immune response — to work, and low amounts of NK cells may explain why these therapies sometimes fail.
NKTR-255 activates the interleukin-15 (IL-15) receptor, which promotes the survival and proliferation of NK cells and other tumor-killing cells, without increasing the activity or numbers of immunosuppressive cells.
The investigational therapy also induces the proliferation of cells responsible for long-term immunological memory, resulting in a sustained anti-tumor response.
IL-15, the molecule that naturally activates the IL-15 receptor, has previously been used as a treatment for cancer, but it is rapidly degraded by the body and requires frequent administration and high doses, which leads to toxicity. NKTR-255 was specifically designed to overcome these challenges.
In preclinical models of lymphoma and myeloma, NKTR-255 showed anti-tumor activity and enhanced the proliferation and activation of NK cells. Combining this investigational treatment with the antibody therapy Darzalex (daratumumab) also increased the toxicity against cancer cells.
“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 [Darzalez] and rituximab,” Lin said.
The Phase 1 trial (NCT04136756) is recruiting up to 82 participants across multiple U.S. sites and will evaluate the safety and efficacy of NKTR-255 in adults with multiple myeloma or non-Hodgkin’s lymphoma.
The study will have two parts: dose escalation and dose expansion. The first part will evaluate the safety and tolerability of escalating doses of NKTR-255 in approximately 40 patients to establish a recommended dose.
The dose-expansion part will divide participants into two groups. The first will continue to receive NKTR-255 alone. The second group will include multiple myeloma patients who have previously received at least three lines of therapy, and they will take NKTR-255 and Darzalex.
Besides safety and efficacy, the trial will evaluate anti-tumor activity, tumor biomarkers, and how NKTR-255 behaves inside the body, focusing on absorption, distribution, metabolism, and excretion.