Investigational Immunotherapy Focus of Phase I Trial in Resistant Myeloma
Posted: Wednesday, January 6, 2021
In a first-in-human study of three patients with heavily pretreated, relapsed or refractory multiple myeloma and one patient with non-Hodgkin lymphoma, the investigational immunotherapy NKTR-255 showed biologic activity and induced a response in the patient with lymphoma and one with multiple myeloma, reported Nina Shah, MD, of the University of California, San Francisco, and colleagues during the 2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 355). The results of this study, published simultaneously in the Journal for ImmunoTherapy of Cancer, also showed the agent was well tolerated.
“In preclinical studies, NKTR-255 enhanced antibody-dependent cellular cytotoxicity…of daratumumab, rituximab, trastuzumab, and cetuximab, resulting in synergistic anticancer activity,” explained the team. NKTR-255 engages interleukin-15 (IL-15) Rα and IL-2/IL-15Rβγ, which lead to natural killer and CD8-positive T-cell expansion, proliferation, and activation, Dr. Shah and colleagues described. As a polymer-conjugated recombinant human IL-15 agonist, the agent maintains the full spectrum of IL-15 biology and reportedly provides sustained pharmacodynamic responses without the need for daily dosing.
The cohort received escalating doses of NKTR-255 intravenously every 3 weeks, and no serious adverse events or dose-limiting toxicities were reported. The patient with non-Hodgkin lymphoma “achieved reduced metabolic activity in all prespecified target lesions after five cycles,” described Dr. Shah and co-investigators. A 63-year-old patient with high-risk, recurrent, stage III multiple myeloma with complex cytogenetics “achieved stable disease after three cycles on NKTR-255 monotherapy,” they continued. He had previously relapsed after receiving other combination regimens.
Together, the preclinical and preliminary clinical data “support continued dose escalation of NKTR-255,” concluded the team. The phase I trial is ongoing.
Disclosure: For full disclosures of the study authors, visit jitc.bmj.com.