Zentalis Pharmaceuticals reports promising results from Phase 1 trial of azenosertib, gemcitabine combo

Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a trailblazer in developing small molecule therapeutics for cancer, has released the final results of its Phase 1 trial combining azenosertib with gemcitabine for relapsed or refractory osteosarcoma. The study findings, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, showcased a notable improvement in event-free survival, signaling a potential breakthrough in treating this aggressive cancer.

Dr. Kimberly Blackwell, Chief Executive Officer at Zentalis, expressed optimism about the trial’s outcomes. “The results from our Phase 1 trial evaluating azenosertib in combination with gemcitabine have demonstrated that this treatment is well-tolerated and clinically effective. We identified an optimal go-forward dose and observed a tripling in event-free survival at 18 weeks compared to historical controls,” said Dr. Blackwell. The promising results have paved the way for further investigation in a Phase 2 trial, specifically targeting patients with this challenging cancer type.

The trial enrolled 31 patients, all evaluable for safety, with most under 39 years of age, reflecting a younger demographic often impacted by osteosarcoma. The 18-week event-free survival rate stood at 39%, a significant increase from the approximately 12% observed in similar historical cohorts. The maximum tolerated dose of azenosertib was established, providing a foundation for the upcoming Phase 2 study.

Azenosertib, a novel inhibitor targeting the WEE1 protein, is critical in regulating cell cycle checkpoints and DNA damage repair. By inhibiting WEE1, azenosertib promotes cell cycle progression in the presence of DNA damage, leading to cancer cell death. This mechanism offers a new approach to treating osteosarcoma, particularly in cases where traditional therapies have failed.

Dr. Viswatej Avutu from the Memorial Sloan Kettering Cancer Center highlighted the need for new therapeutic options. “The management of relapsed and/or refractory osteosarcoma has largely been confined to cytotoxic chemotherapy and recently, tyrosine kinase inhibitors, with limited success. Azenosertib represents a new class of drugs that provides hope for a more effective and tolerable treatment,” stated Dr. Avutu.

With its promising Phase 1 results, Zentalis Pharmaceuticals is set to further explore azenosertib’s efficacy in a Phase 2 trial and additional studies focusing on gynecological malignancies later this year. The ongoing development underscores Zentalis’ commitment to advancing cancer treatment through innovative therapeutic strategies.