FDA Approves Fast Track for ZEN-3694 and Abemaciclib in NUT Carcinoma

On July 14, 2025, the U.S. Food and Drug Administration (FDA) granted fast track designation to ZEN-3694 in combination with abemaciclib (Verzenio) for the treatment of unresectable or metastatic NUT carcinoma, a rare and aggressive cancer that currently has no approved therapies. This designation aims to expedite the development and review of ZEN-3694, offering hope to patients who have exhausted existing treatment options.

NUT carcinoma, characterized by the fusion of the NUTM1 gene with transcriptional regulators, leads to the overexpression of oncogenes, causing unregulated tumor growth. ZEN-3694, a selective BET inhibitor, works by interrupting the activity of the NUT fusion protein, which has demonstrated enhanced antitumor activity when combined with abemaciclib, a CDK4/6 inhibitor (Zenith Epigenetics, 2025).

The FDA's fast track designation is pivotal for accelerating the clinical development of ZEN-3694, as stated by Donald McCaffrey, President and CEO of Zenith Epigenetics: "We are thrilled that the FDA has recognized the strong potential of ZEN-3694 in benefiting patients with NUT carcinoma, an extremely aggressive, deadly cancer, for which there are no effective or approved treatments."

Currently, ZEN-3694 is under evaluation in a phase 1 clinical trial (NCT05372640) that includes both adult and pediatric patients aged 12 years and older with previously treated malignancies, including breast cancer and other solid tumors. The trial aims to evaluate the maximum tolerated dose, response rates, and overall survival outcomes (ClinicalTrials.gov, 2025).

The enrollment criteria for the trial require participants to have a histologically confirmed diagnosis of unresectable or metastatic cancer, with no effective standard treatment available. Patients eligible for this study may have undergone any number of previous therapies, including prior BET inhibitors and CDK4/6 inhibitors, provided they have resolved any acute effects from prior chemotherapy (Zenith Epigenetics, 2025).

The primary endpoints of the trial include defining the recommended phase 2 dose of ZEN-3694, incidence of adverse events (AEs), and overall response rates. Secondary objectives will assess pharmacokinetics and thymidine kinase levels (Zenith Epigenetics, 2025).

The combination therapy of ZEN-3694 and abemaciclib has shown promising results, overcoming common resistance mechanisms observed with monotherapy. Furthermore, the treatment has been well-tolerated, presenting a favorable adverse effect profile, which is crucial for patients undergoing long-term therapy (Zenith Epigenetics, 2025).

The FDA's fast track designation signifies a critical step in the fight against NUT carcinoma, potentially bringing a life-saving treatment option to patients sooner. Zenith Epigenetics is also pursuing orphan drug and breakthrough therapy designations for ZEN-3694, underlining its commitment to developing innovative cancer therapies.

As the clinical trial progresses, the oncology community is hopeful that ZEN-3694, in combination with abemaciclib, will provide a new avenue of treatment for patients grappling with this devastating disease (Zenith Epigenetics, 2025).