Nektar and Syndax, which have new data on immuno-oncology drugs due for presentation at ASCO in the coming days, have agreed to pair them up in a combination trial.
The study will look at how Nektar’s CD122-biased agonist NKTR-214 and Syndax’ HDAC inhibitor entinostat shape up when given as a duo to patients with metastatic melanoma who have previously been treated with a PD-1 inhibitor such as Merck’s Keytruda (pembrolizumab) or Bristol-Myers Squibb’s Opdivo (nivolumab).
It’s some welcome good news for Syndax, which needs to build confidence in entinostat after the publication of the ASCO abstracts earlier this month, and in particular a combination study of entinostat with Keytruda in non-small cell lung cancer with an 11% response rate that disappointed investors and caused its shares to slide.
Nektar will be reporting the results of the phase 1/2 PIVOT trial of NKTR-214 plus Opdivo in patients with advanced solid tumors at ASCO on Saturday, while Syndax is due to report data from several trials of entinostat, including the Keytruda NSCLC study and other trials in pancreatic, colorectal and skin cancer.
The new trial follows the commonly-used approach of a phase 1b stage to determine dosing and a phase 2 efficacy stage that will look at overall response rates, the durability of responses, and other endpoints like progression-free survival and overall survival. It will also use biomarkers to try to gauge the effect of the combo, and particularly blood monocyte levels that—according to Syndax—can be used to predict when patients will respond to therapy.
The company used the monocyte biomarker to identify a subgroup of patients in the Keytruda combination study in NSCLC that had a response rate of 29%, putting a rosier spin on the data, and it will be interesting to see how the ASCO delegates respond to that analysis.
There is already some data backing up the concept of combining Syndax and Nektar’s drugs. At the AACR meeting in April, preclinical data showed that the two drugs were able to block tumor growth in models of kidney and colon cancer, thanks to a hike in the activity of cytotoxic T cells and a reduction in immune suppressor cells in the tumor microenvironment.
If all goes to plan with the phase 1/2 trial, the agreement includes an option to progress to a pivotal study which would be run by Syndax.
Syndax’ CEO Briggs Morrison, M.D., said that “previous phase 2 data with entinostat and high dose IL-2 in renal cell cancer 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.”
In the meantime, the biotech is also pairing the HDAC inhibitor with Roche’s PD-L1 inhibitor Tecentriq (atezolizumab) in triple-negative breast cancer with results due later this year, as well as Merck KGaA/Pfizer’s PD-1 drug Bavencio (avelumab) in ovarian cancer.