On May 30, 2018 Syndax Pharmaceuticals, Inc. (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, and Nektar Therapeutics (Nasdaq: NKTR) reported a non-exclusive, clinical collaboration to evaluate 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 (Press release, Syndax, MAY 30, 2018, View Source [SID1234526966]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
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.
"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," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "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. Working with Nektar allows us to increase the potential impact entinostat may have in the treatment of PD-1 refractory metastatic melanoma patients, and complements the exciting data we have seen when combining entinostat with KEYTRUDA in a similar population."
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.
"The combination of NKTR-214 and entinostat demonstrated a unique synergy in our preclinical models which warrants further study in the clinic," said Jonathan Zalevsky, Ph.D, Senior Vice President and Chief Scientific Officer of Nektar. "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.
About Entinostat
Entinostat is a once-weekly, oral, small molecule, class I HDAC inhibitor currently being evaluated in a Phase 3 clinical trial in combination with exemestane for advanced hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer, an indication for which it has been granted Breakthrough Therapy Designation by the FDA. Entinostat has been shown to block the function of immune suppressive cells in the tumor microenvironment, and is being evaluated in combination with several approved PD-1/PD-L1 antagonists, including in ongoing Phase 1b/2 clinical trials combining entinostat with KEYTRUDA from Merck & Co., Inc. for non-small cell lung cancer, melanoma and colorectal cancer; with TECENTRIQ from Genentech, Inc. for triple negative breast cancer as well as advanced hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer; and with BAVENCIO from Pfizer Inc. and Merck KGaA, Darmstadt, Germany, for ovarian cancer.
About NKTR-214
NKTR-214 is an experimental therapy designed to stimulate cancer-killing immune cells in the body by targeting CD122 specific receptors found on the surface of these immune cells, known as CD8+ effector T cells and Natural Killer (NK) cells. Growing these tumor-infiltrating lymphocytes (TILs) in vivo and replenishing the immune system is critically important as many patients battling cancer lack sufficient TIL populations to benefit from approved checkpoint inhibitor therapies. In preclinical studies, treatment with NKTR-214 resulted in a rapid expansion of these cells and mobilization into the tumor micro-environment.1,2 NKTR-214 has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.