NKTR-255

About NKTR-255

NKTR-255 is an IL-15 receptor agonist designed to activate the IL-15 pathway and expand natural killer (NK) cells and promote the survival and expansion of memory CD8+ T cells without inducing suppressive regulatory T cells. Through optimal engagement of the IL-15Rα/IL-2Rβγ receptor complex, NKTR-255 enhances formation of long-term immunological memory, which may lead to sustained anti-tumor immune response. NKTR-255 is uniquely designed to overcome the challenges of recombinant IL-15, which is rapidly cleared from the body and must be administered frequently and in high doses, limiting its utility due to toxicity and convenience of use.

One of the big challenges in treating cancer patients with targeted monoclonal antibodies is that the cancer patients have a deficiency in key effector cells like NK cells that are needed to work with the monoclonal antibodies.^1,2 In nonclinical studies, NKTR‑255 exhibited anti-tumor activity and substantially enhanced in vivo proliferation and activation of NK cells to provide sustained cytotoxic function.³ In a preclinical lymphoma model where single agent daratumumab was ineffective, NKTR-255 treatment, in combination with daratumumab, increased NK cell numbers and activity in bone marrow tissue and enhanced ADCC-mediated tumor cell clearance in the bone marrow compartment.⁴

In oncology, NKTR-255 is being evaluated in combination with T cell redirection therapies, novel CAR-Ts, anti-HER2 antibodies and anti-CD20 antibodies via an ADCC-focused mechanism in preclinical models of liquid and solid tumors. NKTR-255 is also being evaluated in combination with anti-retroviral and immune modulator therapies through a research collaboration with Gilead.

About the Phase 1 Study

The NKTR-255 Phase 1 study is an open-label, dose escalation and dose expansion study in patients with select hematological malignancies (relapsed or refractory NHL or MM). The dose escalation phase of the study will evaluate the safety and tolerability of NKTR-255 as monotherapy in approximately 40 patients in order to establish a recommended Phase 2 dose (RP2D) for NKTR-255. The dose expansion phase of the study will enroll in two separate cohorts: the first cohort will enroll patients with MM or NHL (relapsed salvage) to evaluate the NKTR-255 RP2D as a monotherapy and the second cohort will enroll patients with MM or NHL (relapsed/refractory salvage) to evaluate the NKTR-255 RP2D in combination with targeted antibodies, including anti-CD38 monoclonal antibody, daratumumab. The study will also evaluate pharmacokinetic and pharmacodynamic effects, anti-tumor activity and biomarker assessments.

For more information, please visit clinicaltrials.gov and search NCT04136756.

¹_{Messaoudene M., et al., (2017) Patient’s Natural Killer Cells in the Era of Targeted Therapies: Role for Tumor Killers. Front. Immunol. 8:683.}

²_{Farnault, L., et al., Hematological Malignancies Escape from NK Cell Innate Immune Surveillance: Mechanisms and Therapeutic Implications. Clinical and Developmental Immunology Volume 2012, Article ID 421702, 8 pages}

³ _{Journal for ImmunoTherapy of Cancer 2017 5(Suppl 2):87; P332.}

⁴_{Miyazaki T., et al., NKTR-255, a polymer-conjugated IL-15 enhances anti-tumor NK cell responses and synergizes with monoclonal antibodies to provide long-term survival in human lymphoma model. In: Proceedings of the Annual Meeting of the AACR; 2019. Abstract 3265.}