Zentalis Pharmaceuticals Presents Updated Clinical Data at the Society of Gynecologic Oncology 2025 Annual Meeting on Women’s Cancer
Zentalis Pharmaceuticals (NASDAQ: ZNTL) has presented updated clinical data from Part 1b of the DENALI trial for azenosertib in platinum-resistant ovarian cancer (PROC) patients at the SGO 2025 Annual Meeting. The trial showed an objective response rate (ORR) of 34.9% in response-evaluable patients with Cyclin E1+ PROC tumors, and a median duration of response (mDOR) of 6.3 months.
The Phase 2 single-arm study evaluated azenosertib monotherapy at 400mg QD 5:2 dose in 102 PROC patients. The data demonstrated Cyclin E1 protein overexpression as a predictive biomarker, with approximately 50% of PROC patients overexpressing Cyclin E1. Common treatment-related adverse events included gastrointestinal toxicities and fatigue.
The company plans to initiate DENALI Part 2 in 1H 2025, with topline data expected by year-end 2026. If successful, the trial could support accelerated approval, subject to FDA review.
Zentalis Pharmaceuticals (NASDAQ: ZNTL) ha presentato dati clinici aggiornati dalla Parte 1b dello studio DENALI per azenosertib in pazienti con cancro ovarico resistente al platino (PROC) durante l'Annual Meeting SGO 2025. Lo studio ha mostrato un tasso di risposta obiettivo (ORR) del 34,9% nei pazienti valutabili in risposta con tumori PROC positivi per Cyclin E1, e una durata mediana della risposta (mDOR) di 6,3 mesi.
Lo studio di fase 2, a braccio singolo, ha valutato la monoterapia con azenosertib a 400 mg QD nel dosaggio 5:2 in 102 pazienti PROC. I dati hanno dimostrato l'iperespressione della proteina Cyclin E1 come biomarcatore predittivo, con circa il 50% dei pazienti PROC che mostrano un'iperespressione di Cyclin E1. Gli eventi avversi comuni correlati al trattamento includevano tossicità gastrointestinali e affaticamento.
L'azienda prevede di avviare la Parte 2 di DENALI nella prima metà del 2025, con dati preliminari attesi entro la fine del 2026. Se avrà successo, lo studio potrebbe supportare un'approvazione accelerata, soggetta alla revisione della FDA.
Zentalis Pharmaceuticals (NASDAQ: ZNTL) ha presentado datos clínicos actualizados de la Parte 1b del ensayo DENALI para azenosertib en pacientes con cáncer de ovario resistente al platino (PROC) en la Reunión Anual SGO 2025. El ensayo mostró una tasa de respuesta objetiva (ORR) del 34,9% en pacientes evaluables en respuesta con tumores PROC positivos para Cyclin E1, y una duración mediana de la respuesta (mDOR) de 6,3 meses.
El estudio de fase 2, de brazo único, evaluó la monoterapia con azenosertib a 400 mg QD en una dosis 5:2 en 102 pacientes PROC. Los datos demostraron la sobreexpresión de la proteína Cyclin E1 como un biomarcador predictivo, con aproximadamente el 50% de los pacientes PROC sobreexpresando Cyclin E1. Los eventos adversos comunes relacionados con el tratamiento incluyeron toxicidades gastrointestinales y fatiga.
La empresa planea iniciar la Parte 2 de DENALI en la primera mitad de 2025, con datos preliminares esperados para finales de 2026. Si tiene éxito, el ensayo podría apoyar una aprobación acelerada, sujeta a la revisión de la FDA.
젠탈리스 제약 (NASDAQ: ZNTL)는 SGO 2025 연례 회의에서 플래티넘 내성 난소암 (PROC) 환자에 대한 아제노세르티브의 DENALI 시험 1b 부분의 업데이트된 임상 데이터를 발표했습니다. 이 시험은 Cyclin E1+ PROC 종양을 가진 반응 평가 가능한 환자에서 객관적 반응률 (ORR) 34.9%를 보여주었으며, 반응의 중간 지속 기간 (mDOR)은 6.3개월입니다.
2상 단일군 연구는 102명의 PROC 환자에게 400mg QD 5:2 용량으로 아제노세르티브 단독 요법을 평가했습니다. 데이터는 Cyclin E1 단백질의 과발현을 예측 바이오마커로 보여주었으며, 약 50%의 PROC 환자가 Cyclin E1을 과발현했습니다. 일반적인 치료 관련 부작용으로는 위장관 독성과 피로가 포함되었습니다.
회사는 2025년 상반기에 DENALI 2부를 시작할 계획이며, 2026년 연말까지 주요 데이터를 기대하고 있습니다. 성공할 경우, 이 시험은 FDA 검토를 조건으로 가속 승인을 지원할 수 있습니다.
Zentalis Pharmaceuticals (NASDAQ: ZNTL) a présenté des données cliniques mises à jour de la Partie 1b de l'essai DENALI pour l'azenosertib chez des patients atteints de cancer de l'ovaire résistant au platine (PROC) lors de la Réunion Annuelle SGO 2025. L'essai a montré un taux de réponse objectif (ORR) de 34,9% chez les patients évaluables en réponse présentant des tumeurs PROC positives pour Cyclin E1, et une durée médiane de réponse (mDOR) de 6,3 mois.
L'étude de phase 2 à bras unique a évalué la monothérapie par azenosertib à 400 mg QD dans un dosage 5:2 chez 102 patients PROC. Les données ont démontré l'hyperexpression de la protéine Cyclin E1 comme biomarqueur prédictif, avec environ 50 % des patients PROC hyper exprimant Cyclin E1. Les événements indésirables courants liés au traitement comprenaient des toxicités gastro-intestinales et de la fatigue.
L'entreprise prévoit de lancer la Partie 2 de DENALI dans la première moitié de 2025, avec des données préliminaires attendues d'ici la fin de 2026. Si l'essai réussit, il pourrait soutenir une approbation accélérée, sous réserve de l'examen de la FDA.
Zentalis Pharmaceuticals (NASDAQ: ZNTL) hat aktualisierte klinische Daten aus Teil 1b der DENALI-Studie für Azenosertib bei platin-resistenten Ovarialkarzinom-Patienten (PROC) auf dem SGO 2025 Jahresmeeting vorgestellt. Die Studie zeigte eine objektive Ansprechrate (ORR) von 34,9% bei ansprechbaren Patienten mit Cyclin E1+ PROC-Tumoren und eine mediane Ansprechdauer (mDOR) von 6,3 Monaten.
Die Phase-2-Studie mit einer einzigen Gruppe bewertete die Monotherapie mit Azenosertib in einer Dosis von 400 mg QD 5:2 bei 102 PROC-Patienten. Die Daten zeigten die Überexpression des Cyclin E1-Proteins als prädiktiven Biomarker, wobei etwa 50% der PROC-Patienten Cyclin E1 überexprimierten. Zu den häufigen behandlungsbedingten Nebenwirkungen gehörten gastrointestinale Toxizitäten und Müdigkeit.
Das Unternehmen plant, die DENALI-Teil 2 in der ersten Hälfte von 2025 zu starten, wobei die ersten Daten bis Ende 2026 erwartet werden. Sollte es erfolgreich sein, könnte die Studie eine beschleunigte Zulassung unterstützen, die der FDA-Prüfung unterliegt.
- Strong 34.9% objective response rate in Cyclin E1+ PROC patients
- Median duration of response of 6.3 months with some responses still ongoing
- Clear biomarker strategy with Cyclin E1 protein overexpression
- Potential accelerated approval pathway identified
- Demonstrated synergistic effects with ADC combinations in preclinical studies
- patient population with only 50% of PROC patients overexpressing Cyclin E1
- Notable adverse events including GI toxicities and fatigue
- Final approval requires additional Phase 3 confirmatory study
- Topline data not expected until end of 2026
Insights
Zentalis Pharmaceuticals has presented updated clinical data for azenosertib that demonstrates continued efficacy in platinum-resistant ovarian cancer (PROC) patients. The 34.9% objective response rate in Cyclin E1+ tumors coupled with a 6.3-month median duration of response represents meaningful clinical activity in a difficult-to-treat patient population.
The company's progression toward Part 2 of the DENALI trial in 1H 2025 establishes a clear development pathway with potential for accelerated approval should results remain consistent. This positions Zentalis with a potential first-in-class WEE1 inhibitor that addresses a specific biomarker-defined subset of patients with treatment options.
The biomarker strategy is particularly noteworthy – by focusing on Cyclin E1 overexpression (estimated in ~50% of PROC patients), Zentalis has identified a specific patient population likely to respond to treatment. This targeted approach aligns with current precision medicine trends that typically receive favorable regulatory consideration.
The preclinical data showing synergistic effects when combined with antibody-drug conjugates (ADCs) suggests potential for expanded market opportunities beyond monotherapy. This creates multiple pathways for commercial success while diversifying clinical development risk.
For a company with a
The updated azenosertib data from DENALI Part 1b represents clinically meaningful activity in platinum-resistant ovarian cancer patients with Cyclin E1 overexpression. The 34.9% response rate in this biomarker-positive population is particularly significant considering the efficacy of current treatments in PROC, where response rates with standard therapies typically range from 10-15%.
The 6.3-month median duration of response adds important context to the efficacy profile. For PROC patients who often experience rapid disease progression, achieving responses lasting over 6 months represents a potentially meaningful clinical benefit. It's worth noting this metric may improve as the data matures, as some patients had ongoing responses at the cutoff date.
Mechanistically, the WEE1 inhibition approach specifically targeting Cyclin E1-overexpressing tumors is scientifically sound. These tumors typically exhibit replication stress and genomic instability, creating vulnerability to cell cycle checkpoint inhibition. The biomarker selection strategy appears robust, with Zentalis developing a proprietary immunohistochemistry cutoff that could identify responders regardless of whether they have CCNE1 gene amplification.
The safety profile remains consistent with previous reports, with gastrointestinal toxicities and fatigue being most common. The intermittent dosing schedule (5 days on, 2 days off) likely helps manage these adverse events while maintaining efficacy.
The preclinical combination data with microtubule inhibitor-based ADCs is mechanistically compelling. By disrupting both cell cycle checkpoints and microtubule dynamics, this approach could overcome resistance mechanisms and enhance tumor cell death while potentially reducing required doses of each agent.
Azenosertib median duration of response (mDOR) updated to 6.3 months in the ongoing DENALI Part 1b clinical trial in patients with platinum-resistant ovarian cancer (PROC) and continues to demonstrate an objective response rate (ORR) of ~
On track to initiate Part 2 of the ongoing DENALI clinical trial in 1H 2025, with registration-intent topline data anticipated by year end 2026
Company also presents preclinical combination data of azenosertib with microtubule inhibitor-based antibody drug conjugates (ADCs) demonstrating synergistic antitumor effects
SAN DIEGO, March 15, 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 updated clinical data from Part 1b of the ongoing DENALI clinical trial of azenosertib in patients with PROC in an oral presentation at the Society of Gynecologic Oncology (SGO) 2025 Annual Meeting on Women’s Cancer.
DENALI Part 1b is a Phase 2 single-arm study that evaluated azenosertib monotherapy at the 400mg QD 5:2 dose (once daily, five days on, two days off, or the “intermittent schedule”) in patients with PROC (n=102).
As of the January 13, 2025 data cutoff, patients with Cyclin E1+ PROC tumors who were response-evaluable (patients who had at least one scan after receiving azenosertib) demonstrated an ORR of
The presentation also demonstrates 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 based on its proprietary immunohistochemistry cutoff.
As of the January 13, 2025 data cutoff, the safety and tolerability profile was consistent with the safety and tolerability profile from the Company’s January 29, 2025 investor event, which included data based off a cutoff date of December 2, 2024, with no new safety findings. Gastrointestinal toxicities and fatigue were found to be the most common treatment-related adverse events.
“The presentation of the updated DENALI Part 1b data at the SGO Annual Meeting supports our continued development of azenosertib,” said Ingmar Bruns, M.D., Chief Medical Officer of Zentalis. “The clear anti-tumor activity and durable response observed highlights the potential of azenosertib to become an important treatment option for patients with Cyclin E1+ PROC. We are proud to have shared these data with many of the world’s leading gynecologic oncologists at SGO as part of our continued commitment to patients living with PROC.”
“Platinum-resistant ovarian cancer is one of the most challenging types of ovarian cancer to treat. Tumors overexpressing Cyclin E1 protein exhibit poorer outcomes after standard of care chemotherapy regimens," said Fiona Simpkins, M.D., Director of Clinical & Translational Gynecologic Oncology Research at the University of Pennsylvania, and lead principal investigator in the DENALI study. “Developing new therapies for this subset of ovarian cancer patients is urgently needed. DENALI Part 1b results are exciting as they show that the WEE1 inhibitor, azenosertib, is active in a Cyclin E1 biomarker selective population potentially addressing a clinical unmet need.”
The Company is on track to initiate enrollment of DENALI Part 2 in the first half of 2025 and expects to disclose topline data from DENALI Part 2 by year end 2026. DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA review. Zentalis plans to treat the same patient population in a Phase 3 randomized confirmatory study, subject to FDA review, which the Company plans to enroll concurrently with DENALI Part 2b.
Tomorrow, the Company will also present preclinical data of azenosertib during a poster presentation at the SGO Annual Meeting. The poster data highlights synergistic effects and significantly improved tumor growth inhibition in in vitro and in vivo preclinical models using a combination of azenosertib and microtubule inhibitor-based ADCs. Together with the previous data that azenosertib synergized with TOPO1 inhibitor based ADCs, these results indicate that azenosertib could be used as a generalizable combination partner with ADCs for improving responses in patients with advanced solid tumors.
The oral presentation and poster can be accessed through the “Publications” section of the Zentalis website.
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 an important treatment option for patients with Cyclin E1+ PROC, the potential for azenosertib to address a clinical unmet need, and the potential for azenosertib to be used as a generalizable combination partner with ADCs for improving responses in patients with advanced solid tumors; our anticipated milestones and the timing thereof, including the anticipated timing of initiation of clinical trials and 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,” “on track,” “opportunity,” “plan,” “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 our lead product candidate, 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 latest efficacy results for azenosertib in the DENALI Part 1b trial for PROC patients?
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