Zentalis Pharmaceuticals to Present Promising Results from Phase 1 Trial of Azenosertib and Gemcitabine in Relapsed or Refractory Osteosarcoma at 2024 American Society of Clinical Oncology Annual Meeting

Administration of azenosertib combined with gemcitabine was well tolerated and resulted in clinically meaningful increase in event-free survival compared to historical comparators

Results support further evaluation of azenosertib combined with gemcitabine in relapsed or refractory osteosarcoma through an investigator-initiated Phase 2 trial

NEW YORK and SAN DIEGO, May 23, 2024 (GLOBE NEWSWIRE) -- Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers, today announced the presentation of final results from a Phase 1 trial of azenosertib and gemcitabine in relapsed or refractory (R/R) osteosarcoma at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

“We are pleased to report the final results from our Phase 1 trial evaluating azenosertib administered with gemcitabine in patients with relapsed or refractory osteosarcoma,” said Kimberly Blackwell, M.D., Chief Executive Officer of Zentalis. “Azenosertib was well tolerated and clinically active in combination with gemcitabine and a go-forward dose was identified. Most importantly, the event-free survival results demonstrate a tripling in the proportion of patients without progression or death at 18 weeks compared with historical control patients. These results support studying the combination in patients facing this aggressive cancer, which we expect will occur in an upcoming investigator-initiated Phase 2 trial. We also look forward to presenting additional data on azenosertib in gynecological malignancies later this year as our development path continues to progress on track.”

Data Highlights and Conclusions:

• 31 patients were enrolled in the study, of which 31 were evaluable for safety, 29 were evaluable for dose-limiting toxicities and 28 were evaluable for efficacy. The median age was 27 (range 12-76) and 21 patients (68%) were ≤39 years old. Patients received a median of 3 (range 1-9) prior therapies, including 10 patients (32%) who had previous treatment with gemcitabine.
• The 18-week event-free survival rate (EFS; time from treatment initiation until disease progression or death due to any cause) was 39% (11/28) across all dose levels. The EFS observed in the study compares favorably to historical cohorts with a similar patient population where a 16-week EFS of ~12% has been reported¹.
• The maximum tolerated dose (MTD) of azenosertib was determined to be 150 mg daily on a 5:2 schedule (5 days on, 2 days off) + gemcitabine 800 mg/m².
• At the MTD, the most frequent grade ≥3 adverse events (≥20%) included thrombocytopenia and lymphopenia (33% each); there were no grade 4 thrombocytopenia events or instances of febrile neutropenia at the MTD.
• Data support further investigation of azenosertib administered in combination with gemcitabine in patients with R/R osteosarcoma in an upcoming investigator-initiated Phase 2 trial.