Zentalis Pharmaceuticals (ZNTL) 7th Annual Oncology Innovation Summit: Insights for ASCO & EHA summary

Key clinical updates and trial insights

• Phase I-B MUIR study of azenosertib plus paclitaxel in platinum-resistant ovarian cancer showed a manageable safety profile and efficacy exceeding historical paclitaxel data; optimal dose identified as 250 mg once daily, five days on, two days off.

• The combination's benefit supports broader application in earlier ovarian cancer lines and other tumor types where taxanes are standard, such as breast and other solid tumors.

• DENALI Part 2 is enrolling to support accelerated approval, with 400 mg five days on, two days off selected as the optimal monotherapy dose based on superior efficacy and comparable safety to 300 mg.

• Part 2C was added to include patients previously treated with taxane regimens, aiming for a representative population and to strengthen the dataset.

• Efficacy expectations for pivotal readout are a response rate of 30% ±5% and duration of response between five and six months, with top-line data expected by year-end.

Safety and tolerability profile

• Safety improvements noted in newer studies, with lower discontinuation rates and no treatment-related Grade 5 events in recent cohorts.

• Adverse events of interest include neutropenia, GI effects, and fatigue, with high-grade events less frequent than with chemotherapy or ADCs.

• The agent does not cause neuropathy, eye toxicity, ILD, or hair loss, differentiating it from other therapies.

• Oral administration offers convenience and independence for patients.

Strategic positioning and future directions

• Azenosertib is positioned as a monotherapy for Cyclin E1-high patients and as a combination partner in ovarian and other cancers.

• Sequencing opportunities exist post-ADC therapy, with potential for combination regimens in evolving treatment landscapes.

• Preclinical data support activity in ADC-resistant models and triple-negative breast cancer, suggesting broader utility.