Following two deaths due to presumed sepsis, the FDA has placed a partial clinical hold on three trials for Zentalis’ azenosertib including a Phase I in solid tumors, Phase II in platinum-resistant ovarian cancer and Phase II in uterine serous carcinoma.
The FDA placed a partial clinical hold on three of Zentalis Pharmaceuticals’ cancer treatment studies following two patient deaths. The company’s stock plunged around 30% in premarket trading Tuesday following the announcement.
Azenosertib, Zentalis’ lead candidate, is in more than 10 ongoing trials as a monotherapy and in combination studies. The FDA’s partial clinical hold impacts a Phase I dose escalation study in solid tumors, a Phase II trial in platinum-resistant ovarian cancer (PROC) and a Phase II study in uterine serous carcinoma (USC). The two recent deaths due to presumed sepsis occurred in the Phase II PROC study, dubbed DENALI.
“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,” Zentalis CEO Kimberly Blackwell said in a statement.
Blackwell noted that more than 500 patients have been treated with the first-in-class small molecule, adding “we believe that our data indicate a favorable therapeutic index that could potentially offer meaningful benefits to women facing PROC and USC.”
Safety and efficacy data are expected later this year from Cohort 1b of the DENALI study, which has completed enrollment with more than 100 patients.
Azenosertib inhibits WEE1, a DNA damage response kinase, with the intention of driving cancer cells into mitosis without the ability to repair damaged DNA, resulting in cell death. To date, there are no WEE1 inhibitors currently approved by the FDA. In addition to testing the small molecule as a monotherapy, Zentalis is also combining it with traditional chemotherapy and DNA damaging agents, as well as molecularly targeted agents in early-stage studies.
The partial clinical hold will not delay Zentalis’ trial in collaboration with GlaxoSmithKline, testing azenosertib with GSK’s PARP inhibitor Zejula in PROC. Topline data from the duo’s Phase I/II MAMMOTH trial are slated for readout in the second half of 2024.
In Zentalis’ first quarter of 2024 financials release in May, the company projected its first NDA for azenosertib would be submitted in 2026 for a “gynecologic malignancy.”
Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.
