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
“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
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.
1 Lagmay JP, et al. J Clin Oncol. 2016;34(25):3031-3038.
“Historically, the management of relapsed and/or refractory osteosarcoma has been limited to cytotoxic chemotherapy and only recently, tyrosine kinase inhibitors, with suboptimal outcomes,” said Viswatej Avutu, M.D., Sarcoma Medical Oncology Service and Pediatric Sarcoma Team,
Study Design
Phase 1 dose-finding study (NCT04833582) assessed azenosertib administered in combination with gemcitabine in patients ≥12 years of age. The primary endpoint was the incidence and severity of dose-limiting toxicities. Secondary endpoints included the incidence and severity of adverse events and EFS at 18 weeks per RECIST v1.1.
Poster Presentation Details:
The full abstract (#11525) is available here on the
Title: Phase 1 Results of the WEE1 Inhibitor, Azenosertib, in Combination With Gemcitabine in Adult and Pediatric Patients With Relapsed or Refractory Osteosarcoma.
Presenter: Dr. Viswatej Avutu, Sarcoma Medical Oncology Service and Pediatric Sarcoma Team,
Session Title: Poster Session – Sarcoma
Session Date and Time:
About Azenosertib
Azenosertib is a novel, selective, and orally bioavailable inhibitor of WEE1 currently being evaluated as a monotherapy and combination clinical studies in ovarian cancer and additional tumor types. WEE1 acts as a master regulator of the G1-S and G2-M cell cycle checkpoints, through negative regulation of both CDK1 and CDK2, to prevent replication of cells with damaged DNA. By inhibiting WEE1, azenosertib enables cell cycle progression, despite high levels of DNA damage, thereby resulting in the accumulation of DNA damage and leading to mitotic catastrophe and cancer cell death.
About
Zentalis® Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers. The Company’s lead product candidate, azenosertib (ZN-c3), is a potentially first-in-class and best-in-class WEE1 inhibitor for advanced solid tumors and hematologic malignancies. Azenosertib is being evaluated as a monotherapy and in combination across multiple clinical trials and has broad franchise potential. In clinical trials, azenosertib has been well tolerated and has demonstrated anti-tumor activity as a single agent across multiple tumor types and in combination with several chemotherapy backbones. As part of its azenosertib clinical development program, the Company is exploring enrichment strategies targeting tumors of high genomic instability, such as Cyclin E1 positive tumors, homologous recombination deficient tumors and tumors with oncogenic driver mutations. The Company is also leveraging its extensive experience and capabilities across cancer biology and medicinal chemistry to advance its research on protein degraders. Zentalis has operations in both
For more information, please visit www.zentalis.com. Follow Zentalis on X/Twitter at @ZentalisP and on LinkedIn at www.linkedin.com/company/zentalis-pharmaceuticals.
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Contact:
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