Zentalis Pharmaceuticals Announces First Patient Dosed in DENALI Part 2 Clinical Trial of Azenosertib in Patients with Cyclin E1+ PROC
Zentalis Pharmaceuticals (ZNTL) has initiated Part 2 of the Phase 2 DENALI clinical trial for azenosertib in patients with Cyclin E1+ platinum-resistant ovarian cancer (PROC). The trial consists of two parts: Part 2a aims to confirm optimal dosing with approximately 30 patients at each of two dose levels (400mg QD 5:2 and 300mg QD 5:2), while Part 2b will enroll about 70 additional patients at the selected dose.
Previous results from Part 1b showed promising outcomes with a 34.9% objective response rate and 6.3-month median duration of response in response-evaluable patients (n=43). The company expects topline data from DENALI Part 2 by year-end 2026, which could potentially support accelerated FDA approval. Zentalis estimates that approximately half of PROC patients overexpress Cyclin E1 protein, making them potential candidates for azenosertib treatment.
Zentalis Pharmaceuticals (ZNTL) ha avviato la Parte 2 dello studio clinico di Fase 2 DENALI per azenosertib in pazienti con carcinoma ovarico resistente al platino (PROC) positivo a Ciclin E1. Lo studio è suddiviso in due fasi: la Parte 2a mira a confermare il dosaggio ottimale con circa 30 pazienti per ciascuno dei due livelli di dose (400mg QD 5:2 e 300mg QD 5:2), mentre la Parte 2b arruolerà circa 70 pazienti aggiuntivi al dosaggio selezionato.
I risultati precedenti della Parte 1b hanno mostrato esiti promettenti con un tasso di risposta obiettiva del 34,9% e una durata mediana della risposta di 6,3 mesi nei pazienti valutabili per la risposta (n=43). L’azienda prevede di ottenere i dati principali della Parte 2 di DENALI entro la fine del 2026, che potrebbero supportare un’approvazione accelerata da parte della FDA. Zentalis stima che circa la metà dei pazienti con PROC sovraesprima la proteina Ciclin E1, rendendoli potenziali candidati al trattamento con azenosertib.
Zentalis Pharmaceuticals (ZNTL) ha iniciado la Parte 2 del ensayo clínico de Fase 2 DENALI para azenosertib en pacientes con cáncer de ovario resistente al platino (PROC) positivo para Ciclin E1. El ensayo consta de dos partes: la Parte 2a tiene como objetivo confirmar la dosis óptima con aproximadamente 30 pacientes en cada uno de dos niveles de dosis (400mg QD 5:2 y 300mg QD 5:2), mientras que la Parte 2b inscribirá a unos 70 pacientes adicionales a la dosis seleccionada.
Los resultados previos de la Parte 1b mostraron resultados prometedores con una tasa de respuesta objetiva del 34,9% y una duración mediana de la respuesta de 6,3 meses en pacientes evaluables para la respuesta (n=43). La compañía espera datos principales de la Parte 2 de DENALI para finales de 2026, lo que podría respaldar una aprobación acelerada por parte de la FDA. Zentalis estima que aproximadamente la mitad de los pacientes con PROC sobreexpresan la proteína Ciclin E1, lo que los convierte en candidatos potenciales para el tratamiento con azenosertib.
Zentalis Pharmaceuticals (ZNTL)는 시클린 E1 양성 백금 내성 난소암(PROC) 환자를 대상으로 하는 아제노서티브 임상 2상 DENALI 시험의 2부를 시작했습니다. 이 시험은 두 부분으로 구성되어 있으며, 2a부는 두 가지 용량 수준(400mg QD 5:2 및 300mg QD 5:2)에서 각각 약 30명의 환자를 대상으로 최적 용량을 확인하는 것이 목표이고, 2b부는 선택된 용량으로 약 70명의 추가 환자를 등록할 예정입니다.
1b부의 이전 결과는 반응 평가 대상 환자(n=43)에서 객관적 반응률 34.9%와 반응 지속 중앙값 6.3개월이라는 유망한 결과를 보여주었습니다. 회사는 2026년 말까지 DENALI 2부의 주요 데이터를 기대하고 있으며, 이는 FDA의 가속 승인 지원에 기여할 수 있습니다. Zentalis는 PROC 환자의 약 절반이 시클린 E1 단백질을 과발현하여 아제노서티브 치료의 잠재적 후보자가 될 것으로 추정합니다.
Zentalis Pharmaceuticals (ZNTL) a lancé la partie 2 de l’essai clinique de phase 2 DENALI pour l’azénosertib chez des patientes atteintes d’un cancer de l’ovaire résistant au platine et positif pour la cycline E1 (PROC). L’essai se compose de deux parties : la partie 2a vise à confirmer la dose optimale avec environ 30 patientes à chacun des deux niveaux de dose (400mg QD 5:2 et 300mg QD 5:2), tandis que la partie 2b recrutera environ 70 patientes supplémentaires à la dose sélectionnée.
Les résultats précédents de la partie 1b ont montré des résultats prometteurs avec un taux de réponse objective de 34,9% et une durée médiane de réponse de 6,3 mois chez les patientes évaluables (n=43). L’entreprise prévoit d’obtenir les données principales de la partie 2 de DENALI d’ici la fin 2026, ce qui pourrait potentiellement soutenir une approbation accélérée par la FDA. Zentalis estime qu’environ la moitié des patientes atteintes de PROC surexpriment la protéine cycline E1, ce qui en fait des candidates potentielles au traitement par azénosertib.
Zentalis Pharmaceuticals (ZNTL) hat den zweiten Teil der Phase-2-Studie DENALI für Azenosertib bei Patienten mit Cyclin E1+ platinresistentem Ovarialkarzinom (PROC) gestartet. Die Studie besteht aus zwei Teilen: Teil 2a soll mit etwa 30 Patienten pro Dosisstufe (400mg QD 5:2 und 300mg QD 5:2) die optimale Dosierung bestätigen, während Teil 2b etwa 70 weitere Patienten mit der ausgewählten Dosis einschließt.
Frühere Ergebnisse aus Teil 1b zeigten vielversprechende Resultate mit einer objektiven Ansprechrate von 34,9% und einer medianen Ansprechdauer von 6,3 Monaten bei bewertbaren Patienten (n=43). Das Unternehmen erwartet die wichtigsten Daten aus Teil 2 von DENALI bis Ende 2026, die eine beschleunigte Zulassung durch die FDA unterstützen könnten. Zentalis schätzt, dass etwa die Hälfte der PROC-Patienten das Cyclin E1-Protein überexprimiert und somit potenzielle Kandidaten für eine Behandlung mit Azenosertib sind.
- 34.9% objective response rate in Part 1b trial shows promising clinical efficacy
- Potential for accelerated FDA approval pathway
- Identified Cyclin E1 as specific predictive biomarker for patient selection
- Large addressable market with ~50% of PROC patients potentially eligible for treatment
- Topline data not expected until end of 2026
- Final FDA approval still subject to review and uncertain
- Median duration of response of 6.3 months is still subject to change
Insights
Zentalis's Phase 2 trial advancement for azenosertib shows promising early efficacy in platinum-resistant ovarian cancer with a strategically targeted biomarker approach.
The initiation of patient dosing in DENALI Part 2 marks a significant milestone in the clinical development pathway for azenosertib in Cyclin E1+ platinum-resistant ovarian cancer (PROC) - a condition with traditionally poor outcomes and treatment options. The registration-intent design with FDA alignment provides a clearer regulatory pathway that could potentially support accelerated approval if successful.
The trial's structured approach is methodically designed: Part 2a will confirm the optimal dose between 300mg and 400mg on an intermittent 5:2 schedule (five days on, two days off), while Part 2b will expand enrollment at the selected dose. The previously disclosed
The company's biomarker strategy targeting Cyclin E1 protein overexpression regardless of gene amplification is particularly noteworthy. This approach represents precision medicine principles by identifying the approximately
However, investors should note the extended timeline - topline data isn't expected until year-end 2026, indicating a significant waiting period before potential commercialization. While the WEE1 inhibition mechanism represents a novel approach in ovarian cancer, and the company positions azenosertib as potentially "first-in-class and best-in-class," the clinical development still carries the inherent risks of any Phase 2 program.
Phase 2 registration-intent trial enrolling Part 2a dose confirmation arms
Topline data from DENALI Part 2 anticipated by year end 2026 with the potential to support an accelerated approval, subject to FDA feedback
SAN DIEGO, April 28, 2025 (GLOBE NEWSWIRE) -- Zentalis® Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company developing a potentially first-in-class and best-in-class WEE1 inhibitor for patients with ovarian cancer and other tumor types, today announced that the first patient has been dosed in Part 2 of the Phase 2 DENALI clinical trial (NCT05128825) of azenosertib in patients with Cyclin E1+ platinum-resistant ovarian cancer (PROC).
As previously disclosed, the Company aligned with the U.S. Food and Drug Administration (FDA) on the design of DENALI Part 2, which allows for seamless enrollment in the two parts of the trial:
- Part 2a is designed to confirm the primary dose-of-interest with a target enrollment of approximately 30 patients at each of two dose levels: 400mg QD 5:2 and 300mg QD 5:2 (intermittent daily dosing on a five days on, two days off dosing schedule).
- Part 2b is designed to enroll approximately 70 additional patients at the selected dose, which will be informed by the Part 2a results, subject to FDA feedback.
The Company expects to disclose topline data from DENALI Part 2 by year end 2026 and if successful, this trial has the potential to support an accelerated approval, subject to FDA review.
“Dosing the first patient in Part 2 of the DENALI study is an important milestone for Zentalis as we continue the clinical development of azenosertib,” said Ingmar Bruns, M.D., Chief Medical Officer of Zentalis. “We are proud that azenosertib is one step closer to our goal of addressing a tremendous unmet need. We are grateful to our patients and their families for participating in this trial, which has the potential to result in a treatment option for thousands of women diagnosed with Cyclin E1+ PROC.”
Previously disclosed clinical data from Part 1b of the DENALI study showed clinically meaningful results in patients with Cyclin E1+ PROC. As of the January 13, 2025 data cutoff, patients who were response-evaluable (n=43) had an objective response rate (ORR) of
The data also established Cyclin E1 protein overexpression, regardless of CCNE1 gene amplification, as a sensitive and specific predictive biomarker that can be used to identify patients who could potentially derive benefit from azenosertib. Zentalis estimates that about half of PROC patients overexpress Cyclin E1 protein based on its proprietary immunohistochemistry cutoff.
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
Zentalis® Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing azenosertib (ZN-c3), a potentially first-in-class and best-in-class WEE1 inhibitor for patients with Cyclin E1+ platinum-resistant ovarian cancer (PROC). Azenosertib is being evaluated as a monotherapy and in combination across multiple tumor types in 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. The Company is also leveraging its extensive experience and capabilities to translate its science to advance research on additional areas of opportunity for azenosertib outside PROC. Zentalis has operations in San Diego.
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
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, but not limited to, statements regarding the potential of azenosertib, including the potential for azenosertib to become a treatment option for women with Cyclin E1+ PROC, our goal for azenosertib to address a tremendous unmet need; our anticipated milestones and the timing thereof, including the timing of clinical data disclosures; the potential to advance research on additional areas of opportunity for azenosertib outside PROC; the potential for azenosertib to be first-in-class and best-in-class; the potential for Cyclin E1 to serve as a sensitive and predictive biomarker that can be used to identify patients who could potentially derive benefit from azenosertib; our estimate of how many PROC patients overexpress Cyclin E1 based on our proprietary immunohistochemistry cutoff; and our planned clinical development strategy and regulatory strategy for azenosertib and the timing thereof, including plans for registration-intent studies and the potential for DENALI Part 2 to support an accelerated approval. The terms “anticipated,” “can,” “could,” “estimate,” “expect,” “intent,” “opportunity,” “potential,” and “will” and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our limited operating history, which may make it difficult to evaluate our current business and predict our future success and viability; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; our plans, including the costs thereof, of development of companion diagnostics; our substantial dependence on the success of azenosertib; the outcome of preclinical testing and early trials may not be predictive of the success of later clinical trials; failure to identify additional product candidates and develop or commercialize marketable products; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process or ongoing regulatory obligations; failure to obtain U.S. or international marketing approval; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; effects of significant competition; the possibility of system failures or security breaches; risks relating to intellectual property; our ability to attract, retain and motivate qualified personnel, and risks relating to management transitions; significant costs as a result of operating as a public company; and the other important factors discussed under the caption “Risk Factors” in our most recently filed periodic report on Form 10-K or 10-Q and subsequent filings with the U.S. Securities and Exchange Commission (SEC) and our other filings with the SEC. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.
ZENTALIS® and its associated logo are trademarks of Zentalis and/or its affiliates. All website addresses and other links in this press release are for information only and are not intended to be an active link or to incorporate any website or other information into this press release.
Contact:
Haibo Wang - Chief Business Officer
Ron Moldaver - Investor Relations
ir@zentalis.com
FAQ
What are the key results from DENALI Part 1b trial for ZNTL's azenosertib?
When will Zentalis (ZNTL) release topline data for DENALI Part 2?
How many patients will be enrolled in DENALI Part 2 clinical trial?
What percentage of PROC patients could potentially benefit from azenosertib treatment?
What are the dosing levels being tested in DENALI Part 2a for ZNTL's azenosertib?
