Following the success of a phase 1 study that showed its potential for accelerated FDA approval in the future, the WEE-1 inhibitor, ZN-c3 has been dosed for the first time in the newly launched phase 2 study, which is exploring the agent for the treatment of adult women with recurrent or persistent uterine serous carcinoma.
Following the success of a phase 1 study that showed its potential for accelerated FDA approval in the future, the WEE-1 inhibitor, ZN-c3 has been dosed for the first time in the newly launched phase 2 study, which is exploring the agent for the treatment of adult women with recurrent or persistent uterine serous carcinoma (USC).1
“This trial, with its potential accelerated approval pathway, underscores our potential ability to efficiently develop and advance promising therapeutic candidates in hopes of delivering them to patients quickly,” said Anthony Sun, MD, chairman and chief executive officer of Zentalis Pharmaceuticals, in a statement.
Zentails Pharmaceuticals announced in a press release that the open-label, multicenter phase 2, study (NCT04814108) will assess the clinical activity, safety, pharmacokinetics, and related biomarkers of ZN-c3 in patients with recurrent or persistent USC. The estimated study enrollment is 100 patients who will be evaluated for the primary end point of objective response rate per RECIST v1.1, and the secondary end points of duration of response (DOR), progression-free survival (PFS), and the safety and tolerability defined by the severity and frequency of adverse events (AEs).
“Dosing the first patient in this phase 2 trial is an important next step toward our goal of developing a safe and effective therapy for the thousands of women in the U.S. diagnosed with USC annually. Despite current treatment options, USC–a highly aggressive form of endometrial cancer–has an extremely poor prognosis, with survival rates ranging between 30% to 50%. We believe that our potentially first- and best-in-class oral WEE1 inhibitor, ZN-c3, represents one of the most promising clinical advances in DNA damage response and synthetic lethality to date, and if successfully developed and approved, has the potential to redefine the USC treatment landscape.”
In the previous phase 1 study, ZN-c3 demonstrated an early signal of clinical activity in heavily pretreated patients with advanced solid tumors. The agent was also found to be safe and tolerable in these patients.2
A total of 39 patients were treated and evaluated on ZN-c3 in the phase 1 study. Sixteen of the patients had baseline tumor assessment and of those individuals, stable disease was seen in 5 and partial responses (PRs) were achieved in 2 of them following treatment with ZN-c3. Further, a 42% reduction in tumor burden was observed in 1 patient with colorectal cancer and metastases in the liver, lymphoma nodes, and pleura after achieving a PR.
Most patients experienced a treatment-related AE (TRAE) during the study (n = 30). Nausea, diarrhea, vomiting, and fatigue were the most frequently reported TRAEs.
The phase 2 study is further evaluating the promising results observed in phase 1. There is also research ongoing to determine mechanisms of response and potential biomarker use.
ZN-c3 is believed to be a first-in-class and best-in-class oral WEE-1 inhibitor. The drug works by preventing tumor growth and causing tumor regression by generating DNA damage in the cancer cells. Outside of the gynecologic cancer space, ZN-c3 has received orphan drug designation and rare pediatric disease designation by the FDA for pediatric osteosarcoma.1
The phase 2 study of ZN-c3 is recruiting female patients aged 18 years or older with recurrent of persistent USC, and ECOG performance status of 0 or 1, measurable disease per RECIST v1.1, and adequate hematologic and organ function who agree to take effective contraception. Patients are actively being recruited at study sites in Michigan and Wisconsin.
The estimated completion date of the study is December 1, 2023.
1. Zentalis Pharmaceuticals announces first patient dosed in potentially registrational phase 2 study of ZN-c3 in patients with uterine serous carcinoma. News release. Zentalis Pharmaceuticals. August 2, 2021. Accessed August 3, 2021. https://bit.ly/3jlG9tZ
2. Tolcher A, Mamdani H, Chalasani P, et al. Abstract CT016: Clinical activity of single-agent ZN-c3, an oral WEE1 inhibitor, in a phase 1 dose-escalation trial in patients with advanced solid tumors. Cancer Res. 2021; 81 (Suppl 13): CT016. doi: 10.1158/1538-7445.AM2021-CT016