Syndax’s HDAC inhibitor entinostat missed its primary endpoints in a pair of phase 1b/2 trials combining it with anti-PD-1 drugs from Genentech and Merck KGaA and Pfizer. The company will now “defer advancement” of its entinostat/PD-1 combination programs so it can throw its weight behind leukemia drug SNDX-5613 and its entinostat program in HR-positive breast cancer.
The first trial, ENCORE 602, tested entinostat with Genentech’s Tecentriq in patients with triple-negative breast cancer, and the second trial, ENCORE 603, tested it alongside Merck KGaA and Pfizer’s Bavencio in patients with ovarian cancer. The combinations failed to improve progression-free survival in both studies, Syndax said in its fourth-quarter update.
Waltham, Massachusetts-based Syndax is also pairing entinostat with Merck’s Keytruda; the combination is in the clinic for non-small cell lung cancer, colorectal cancer and melanoma. It, too, will be put on hold while Syndax works on its E2112 program, a combination of entinostat and the hormone therapy exemestane, which is currently in a phase 3 study for HR-positive, HER2-negative, metastatic breast cancer.
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"While we are encouraged by ENCORE 601 entinostat-KEYTRUDA combination data in NSCLC and melanoma which suggests that entinostat has the ability to overcome resistance in PD-1 refractory patients, we believe that it is in the best interest of our stakeholders to prioritize our resources ahead of the E2112 OS readout, at which time we will make a determination on next steps for the I-O combination program,” said Syndax CEO Briggs Morrison, M.D., in the statement.
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Once it has E2112 data in hand, Syndax will decide if it wants to advance its entinostat/PD-1 programs into one or more registration trials, the company said. It expects the next interim analysis in the second quarter of 2019.