FDA Fast Track Designation Accelerates Novel Therapy for NUT Carcinoma

Zenith Epigenetics announced that its lead clinical candidate, ZEN-3694, has received fast track designation from the FDA for the treatment of metastatic or unresectable NUT carcinoma. This designation applies to ZEN-3694 when used in combination with abemaciclib (Verzenio) in patients who have received at least 1 prior line of chemotherapy. This is a significant development for an aggressive and deadly cancer with no currently approved treatments.

The FDA's fast track program aims to expedite the development and review of drugs that treat serious conditions and fill an unmet medical need. Benefits of this designation for ZEN-3694 include more frequent interactions with the FDA and eligibility for accelerated approval and priority review, all of which are designed to bring this potential therapy to patients more rapidly.

"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," said Donald McCaffrey, president and CEO of Zenith Epigenetics, in a press release. "Fast track designation will accelerate ZEN-3694's clinical NUT carcinoma program by expediting its development and review and allow us to deliver this potentially life-saving drug to patients sooner."

NUT carcinoma can affect both adults and children, primarily manifesting in the head, neck, and thoracic regions. Despite its rarity, it is estimated that up to 10,000 cases may occur annually, and it is frequently underdiagnosed. The prognosis for patients with NUT carcinoma is exceptionally poor, with a median overall survival of approximately 6 months, underscoring the critical unmet medical need that ZEN-3694 aims to address.

ZEN-3694 is an orally available BET inhibitor, representing a targeted approach to disrupting the molecular drivers of NUT carcinoma. The drug functions by interfering with the activity of the NUT fusion protein, which is known to aberrantly drive oncogenic gene expression in this particular cancer. Preclinical and early clinical data suggest that ZEN-3694 possesses both single-agent activity and enhanced efficacy when used in combination with other agents.

Notably, the combination of ZEN-3694 and abemaciclib has demonstrated superior response rates and duration of response compared to single-agent BET inhibitors in prior investigations. This synergistic effect is particularly promising given the aggressive nature of NUT carcinoma and the limited efficacy of existing chemotherapy regimens. The therapeutic rationale for combining a BET inhibitor with abemaciclib, a CDK4/6 inhibitor, is rooted in targeting distinct yet convergent pathways that contribute to cell proliferation and survival in cancer.

ZEN-3694 is currently being evaluated in two active clinical trials for NUT carcinoma. One trial (NCT05372640) investigates ZEN-3694 in combination with abemaciclib, directly aligning with the fast track designation. Another ongoing trial (NCT05019716) explores ZEN-3694 in combination with cisplatin and etoposide, a conventional chemotherapy backbone often used in aggressive solid tumors. These trials are crucial for establishing the safety and efficacy profile of ZEN-3694 in various therapeutic contexts for NUT carcinoma.

REFERENCE:

FDA grants Zenith’s ZEN-3694 fast track status. News release. Zenith Epigenetics. July 14, 2025. Accessed July 15, 2025. https://tinyurl.com/2kf5uvmz