The partnership will assess the safety and efficacy of Nektar's NKTR-214, a CD122-biased agonist, in combination with entinostat, Syndax's oral, small molecule Class 1 specific HDAC inhibitor, in patients with metastatic melanoma who have previously progressed on treatment with an anti-PD-1 (programmed death receptor-1) agent.
Under the terms of the agreement, Syndax and Nektar will collaborate on a study to evaluate the combination. The Phase 1b portion of the trial aims to establish safety and a recommended dose for the combination regimen and will be followed by a Phase 2 portion designed to assess efficacy, as defined by objective response rate and durability of response.
Progression free survival and overall survival will also be evaluated. Correlative biomarker analyses that aim to identify patients with enhanced responses to the combination, including analyses exploring the potential of elevated levels of classical peripheral blood monocytes, will be incorporated.
Syndax will be responsible for conducting the Phase 1b/2 trial and the agreement includes a provision where the parties may extend the collaboration to include a pivotal trial based on mutual interest.
Syndax CEO Briggs Morrison said: “We are excited to be working with Nektar as we build upon our strategy of establishing clinical collaborations to test novel combinations of entinostat with leading edge immune therapies.
“Previous Phase 2 data with entinostat and high dose IL-2 in renal cell cancer1 and our promising preclinical data generated with NKTR-214, laid the scientific and clinical foundation for this collaboration.”
In preclinical testing, the results of which were recently presented at the 2018 American Association of Cancer Research Annual Meeting2, the combination of entinostat and NKTR-214 significantly inhibited tumor growth in tumor models of kidney and colon cancer.
The anti-tumor activity of the combination was accompanied by a dramatic increase in the activation and cytotoxic activity of CD8+ T cells in the tumor, along with modulation of immune suppressor cells found in the tumor microenvironment.
Nektar senior vice president and chief scientific officer Dr Jonathan Zalevsky said: "The combination of NKTR-214 and entinostat demonstrated a unique synergy in our preclinical models which warrants further study in the clinic.
"Importantly, we observed elevated levels of cytokine-positive tumor-infiltrating cytotoxic T cells following treatment with the combination. We believe this important preclinical finding could translate to improved tumor responses in patients who have become refractory to checkpoint inhibitors. We look forward to working with Syndax as this combination advances into the clinic."
Additional financial details and other terms of the agreement were not disclosed.
Source: Company Press Release