Dr Westin on Early Findings With Azenosertib in High-Grade Serous Ovarian Cancer


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Shannon N. Westin, MD, MPH, FACOG, discusses the DENALI trial of azenosertib in patients with high-grade serous ovarian cancer.

Shannon N. Westin, MD, MPH, FACOG, director, Early Drug Development, clinical medical director, professor, Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, codirector, Ovarian Cancer Moonshot Program, The University of Texas MD Anderson Cancer Center, discusses the potential implications of the phase 2 DENALI trial (NCT05128825) of azenosertib (ZN-c3) in patients with high-grade serous ovarian, fallopian tube, or primary peritoneal cancer.

Early data from the phase 1 ZN-c3-001 study (NCT04158336) have been reported, Westin says. This trial was designed to identify the optimal dose and treatment schedule of azenosertib, Westin explains. Azenosertib does not need to be administered daily; instead, it is given on an intermittent schedule, Westin notes. During the phase 1 portion, early efficacy signals with the agent were alsoobserved in patients with ovarian cancer, as well as those with uterine cancer and other solid tumors, Westin adds.

To be eligible for enrollment in DENALI, patients with ovarian cancer must have received between 1 and 4 prior lines of therapy. This included prior treatment with bevacizumab (Avastin), as bevacizumab is one of the most active agents in platinum-resistant disease, Westin says. Bevacizumab is typically administered in combination with chemotherapy, such as weekly paclitaxel. Regarding other potential prior lines of therapy, mirvetuximab soravtansine-gynx (Elahere) is an FDA-approved antibody-drug conjugate for patients with folate receptor α (FRα)–high, platinum-resistant ovarian cancer. This disease subtype comprises approximately 20% to 30% of the total ovarian cancer population, according to Westin. Patients who do not have FRα-positive disease may have received other lines of chemotherapy or investigational agents as part of clinical trials, Westin explains.

The DENALI trial is an important research opportunity for patients with ovarian cancer, Westin emphasizes. Going forward, investigators will aim to determine whether azenosertib is active regardless of patients’ CCNE1 amplification status or whether it is only effective in patients with CCNE1-amplified disease, Westin says. Although azenosertib is a promising novel agent for ovarian cancer, it should only be given to patients in whom it will be effective, Westin notes. Ongoing research, including DENALI, may help identify the patient subgroup that will derive the most benefit from the agent, according to Westin. Future investigations may discover biomarkers beyond CCNE1 and FRα that may be leveraged in other patient populations, Westin concludes.

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