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Zenith Epigenetics to Explore BET Inhibitor Combinations in Multiple NCI-Sponsored Trials

NEW YORK – Zenith Epigenetics on Wednesday said it will begin seven National Cancer Institute-sponsored clinical trials of its BET inhibitor ZEN-3694 in biomarker-defined cancers.

The trials will evaluate ZEN-3694 in combination with other drugs, including targeted therapy, immunotherapy, and chemotherapy. Zenith is working with the NCI's Cancer Therapy Evaluation Program to conduct the trials.

"A rich translational program is embedded in each trial to validate the mechanism of action and identify markers of response and resistance," the Calgary, Alberta-based firm said in a statement.

In a Phase Ib trial, the company is exploring the activity of ZEN-3694 with Merck's Keytruda (pembrolizumab) and nab-paclitaxel chemotherapy in patients with metastatic triple-negative breast cancer whose tumors are PD-L1 negative.

Another Phase I/Ib trial will evaluate ZEN-3694 plus Bristol Myers Squibb's Opdivo (nivolumab), with or without BMS's Yervoy (ipilimumab) in patients with advanced solid tumors and BRCA wild-type platinum-resistant ovarian cancer. In this trial, researchers will track patients' outcomes based on their circulating tumor DNA, as well as their PD-L1, CCNE1, MYC, and BRD4 expression before and after treatment.

In a Phase II trial, Zenith will evaluate ZEN-3694 in combination with Pfizer's PARP inhibitor Talzenna (talazoparib) in a range of solid tumor types, including cancers with alterations in KRAS, and BRCA1/2 or other DNA damage response genes.

And in a Phase I study, Zenith will pair ZEN-3694 with Pfizer's MEK inhibitor Mektovi (binimetinib) in patients with triple-negative breast cancer and in patients with RAS pathway-altered solid tumors, including mutations in KRAS, NRAS, HRAS, or BRAF, inactivating NF1 mutations, and BRAF fusions.

Additional NCI-sponsored trials will evaluate ZEN-3694 in combination with chemotherapy and the BET inhibitor with CDK4/6 inhibitors in nuclear protein in testis (NUT) carcinoma, as well as with Syndax's HDAC inhibitor entinostat in advanced and refractory solid tumors and lymphomas.

Separate from these NCI-sponsored trials, Zenith also has two ongoing programs involving ZEN-3694. In one program, it is exploring ZEN-3694 with Astellas/Pfizer's Xtandi (enzalutamide) with or without Keytruda in metastatic castration-resistant prostate cancer. In another Phase II program, ZEN-3694 is being studied with Talzenna in triple-negative breast cancer.