Syndax hits pause on entinostat/PD-1 program after midstage failures

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Waltham, Massachusetts-based Syndax is also pairing entinostat with Merck’s Keytruda, but that program will also be on hold as the company focuses on its breast cancer program. (kai kalhh)

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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RELATED: Syndax claims biomarker predicts increased benefit of HDAC/PD-1 combination in NSCLC

"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.

RELATED: Despite ASCO wobble, Syndax pals up with Nektar on entinostat combo trial

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. 

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