FDA Imposes Partial Hold on Zentalis Cancer Trials Following Patient Deaths

The FDA has imposed a partial clinical hold on three cancer treatment studies conducted by Zentalis Pharmaceuticals following the deaths of two patients. This announcement led to a significant drop in the company's stock, which fell by approximately 30% in premarket trading on Tuesday.

Azenosertib, the leading candidate from Zentalis, is undergoing more than ten different trials, both as a standalone treatment and in combination with other therapies. The FDA's partial clinical hold affects three specific studies: a Phase I dose escalation study for solid tumors, a Phase II trial for platinum-resistant ovarian cancer (PROC), and a Phase II study for uterine serous carcinoma (USC). The two patient deaths occurred during the Phase II PROC study, known as DENALI, and were attributed to presumed sepsis.

Zentalis CEO Kimberly Blackwell emphasized the company's commitment to patient safety, stating, "Patient safety is our top priority and any deaths that occur in the setting of clinical trials are unfortunate. We are working closely with the FDA to resolve this partial clinical hold as quickly as possible." She added that over 500 patients have been treated with azenosertib, a first-in-class small molecule. Blackwell also noted that the data gathered so far suggest a favorable therapeutic index, which could offer significant benefits to women facing PROC and USC.

Further safety and efficacy data from the DENALI study's Cohort 1b, which has over 100 enrolled patients, are anticipated later this year. Azenosertib functions by inhibiting WEE1, a DNA damage response kinase, pushing cancer cells into mitosis without the capacity to repair damaged DNA, thus leading to cell death. Currently, there are no FDA-approved WEE1 inhibitors. Zentalis is exploring azenosertib not just as a monotherapy but also in combination with traditional chemotherapy, DNA-damaging agents, and molecularly targeted therapies in early-stage studies.

The partial clinical hold will not affect Zentalis' ongoing trial with GlaxoSmithKline, which is testing azenosertib in combination with GSK’s PARP inhibitor Zejula for PROC. The initial results from the Phase I/II MAMMOTH trial are expected in the latter half of 2024.

In its financial report for the first quarter of 2024, released in May, Zentalis projected that the first New Drug Application (NDA) for azenosertib would be submitted in 2026 for a gynecologic malignancy.