ASCO: Zentalis showcases ovarian cancer data that will take WEE1 to phase 3
26 May 2023
Clinical ResultASCOPhase 3Phase 2Phase 1
Preview
Source: FierceBiotech
New data are enough for Zentalis Pharmaceuticals to begin preparations for a phase 3 study comparing azenosertib dosed intermittently in combination with either carboplatin or paclitaxel.
A year after getting Pfizer’s backing, Zentalis Pharmaceuticals says new data for a WEE1 candidate justifies putting the asset into a phase 3 study for ovarian cancer next year.
The phase 1b trial enrolled 115 patients with platinum-resistant ovarian cancer, of which 94 were evaluable by the April 10 cutoff. The findings—published in an abstract ahead of this year’s American Society of Clinical Oncology annual meeting—showed that the synthetic lethal WEE1 inhibitorWEE1 inhibitor azenosertib plus the chemotherapy paclitaxel produced an overall response rate (ORR) of 50%.
When given in a regimen with other chemotherapies like gemcitabine or carboplatin, the WEE1 candidate demonstrated an ORR of 38.5% and 35.7%, respectively. A regimen with pegylated liposomal doxorubicin posted the lowest ORR at 19.4%.
As for median progression-free survival (mPFS), azenosertib plus carboplatin came out on top at 10.4 months, followed by azenosertib plus gemcitabine at 8.3 months. The regimens that included paclitaxel and pegylated liposomal doxorubicin only saw mPFS of 7.4 months and 6.3 months, respectively.
Zentalis was also able to test for expression of the Cyclin E1 protein in 82 of the patients and the biotech noted that Cyclin E1+ status was associated with a superior ORR and a longer mPFS. This finding “showcase[es] the potential synergy of WEE1 inhibition with chemotherapy in this patient population,” the biotech concluded.
The most common treatment-related adverse events of grade 3 or above across all cohorts were thrombocytopenia (27.5%), neutropenia (25.5%), anemia (15.7%) and fatigue (9.8%).
The data are enough for Zentalis to begin preparations for a phase 3 study comparing azenosertib dosed intermittently in combination with either carboplatin or paclitaxel in patients with Cyclin E1+status and with platinum-sensitive ovarian cancer. The biotech expects to launch the late-stage trial in the first quarter of 2024.
“Azenosertib is emerging as a very promising clinical candidate, with demonstrated anti-tumor activity in difficult-to-treat tumor types when used in combination with standard chemotherapy regimens,” Zentalis CEO Kimberly Blackwell, M.D., said in the release. “The addition of azenosertib increased ORRs and mPFS over those observed historically with chemotherapy alone, or compared to adavosertib in combination with chemotherapy.”
Despite Pfizer throwing its weight behind ZentalisZentalis with a $25 million investment in April 2022, the biotech was able to retain full economic ownership of azenosertib, then known as ZN-c3. At the time, Zentalis said it planned to use the Big Pharma’s cash to support clinical trials of azenosertib and ZN-d5, an oral inhibitor of BCL-2 in development in blood cancers including acute myeloid leukemia and non-Hodgkin lymphoma.
WEE1 enzymes play a role in the DNA damage response, or DDR, pathway. The idea behind WEE1 inhibitorsWEE1 inhibitors is that they could boost the efficacy of DNA-damaging therapies by forcing tumors to replicate damaged DNA before it is fixed.
For more details,please visit the original website
The content of the article does not represent any opinions of Synapse and its affiliated companies. If there is any copyright infringement or error, please contact us, and we will deal with it within 24 hours.
Organizations
Drugs
Hot reports
Get started for free today!
Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.
Start your data trial now!
Synapse data is also accessible to external entities via APIs or data packages. Leverages most recent intelligence information, enabling fullest potential.