Kronos Bio Announces First Patient Dosed with KB-0742 in an Expansion Cohort Focused on Platinum-Resistant High-Grade Serous Ovarian Cancer
Kronos Bio (NASDAQ: KRON) has dosed the first patient in an expansion cohort of its KB-0742 clinical trial, focusing on platinum-resistant high-grade serous ovarian cancer (HGSOC). The trial uses an 80mg dose on a four-days-on, three-days-off schedule, which cleared the dose escalation phase. This dosing regimen is expected to provide a 1.8-fold increase in AUC compared to the previous 60mg three-days-on, four-days-off schedule.
KB-0742 has shown a favorable safety profile in over 100 patients, with no grade 3 or 4 neutropenia observed. The company plans to provide an efficacy update on this expansion cohort in the first half of 2025. HGSOC is particularly sensitive to CDK9 inhibition due to MYC amplification or overexpression and homologous recombination deficiencies, affecting a significant portion of ovarian cancer patients.
Kronos Bio (NASDAQ: KRON) ha somministrato il primo trattamento al paziente di una coorte di espansione del suo trial clinico KB-0742, focalizzandosi sul cancro ovarico seroso di alto grado resistente al platino (HGSOC). Il trial utilizza una dose di 80mg seguendo un programma di quattro giorni di trattamento seguiti da tre giorni di pausa, che ha superato la fase di escalation della dose. Questo schema di dosaggio prevede un aumento di 1,8 volte dell'AUC rispetto al precedente schema di 60mg con tre giorni di trattamento e quattro di pausa.
KB-0742 ha mostrato un profilo di sicurezza favorevole in oltre 100 pazienti, con nessun caso di neutropenia di grado 3 o 4 osservato. L'azienda prevede di fornire un aggiornamento sull'efficacia di questa coorte di espansione nella prima metà del 2025. L'HGSOC è particolarmente sensibile all'inibizione del CDK9 a causa dell'amplificazione o sovraespressione di MYC e delle difetti di ricombinazione omologa, che colpiscono una parte significativa dei pazienti con cancro ovarico.
Kronos Bio (NASDAQ: KRON) ha administrado la primera dosis al paciente en una cohorte de expansión de su ensayo clínico KB-0742, centrado en el cáncer de ovario seroso de alto grado resistente al platino (HGSOC). El ensayo utiliza una dosis de 80 mg con un esquema de cuatro días de tratamiento seguido de tres días de descanso, que ha superado la fase de escalada de la dosis. Este régimen de dosificación se espera que proporcione un incremento de 1.8 veces en el AUC en comparación con el anterior esquema de 60 mg con tres días de tratamiento y cuatro días de descanso.
KB-0742 ha demostrado un perfil de seguridad favorable en más de 100 pacientes, sin neutropenia de grado 3 o 4 observada. La compañía planea proporcionar una actualización de eficacia sobre esta cohorte de expansión en la primera mitad de 2025. El HGSOC es particularmente sensible a la inhibición del CDK9 debido a la amplificación o sobreexpresión de MYC y a deficiencias de recombinación homóloga, que afectan a una parte significativa de los pacientes con cáncer de ovario.
크로노스 바이오 (NASDAQ: KRON)는 백금 저항성 고급 성계란 암(HGSOC)에 중점을 두고 KB-0742 임상 시험의 확장 코호트에서 첫 번째 환자에게 투여하였습니다. 이번 시험은 4일 치료 후 3일 휴식으로 구성된 80mg 용량을 사용하며, 이 용량 증량 단계를 통과했습니다. 이 용량 일정은 이전의 60mg, 3일 치료 후 4일 휴식 일정과 비교하여 AUC가 1.8배 증가할 것으로 기대됩니다.
KB-0742는 100명 이상의 환자에서 유리한 안전 프로필을 보여주었으며, 3급 또는 4급 호중구감소증은 관찰되지 않았습니다. 회사는 2025년 상반기에 이 확장 코호트에 대한 효능 업데이트를 제공할 계획입니다. HGSOC는 MYC 증폭 또는 과발현 및 동원자 교환 결핍으로 인해 CDK9 억제에 특히 민감하여, 이는 난소암 환자의 상당 부분에 영향을 미칩니다.
Kronos Bio (NASDAQ: KRON) a administré la première dose à un patient dans une cohorte d'expansion de son essai clinique KB-0742, se concentrant sur le cancer de l'ovaire séreux de haut grade résistant au platine (HGSOC). L'essai utilise une dose de 80mg selon un calendrier de quatre jours de traitement suivis de trois jours de repos, qui a franchi la phase d'escalade de dose. Ce schéma de posologie devrait permettre une augmentation de 1,8 fois de l'AUC par rapport à l'ancien schéma de 60mg en trois jours de traitement et quatre jours de repos.
KB-0742 a montré un profil de sécurité favorable chez plus de 100 patients, sans neutropénie de grade 3 ou 4 observée. La société prévoit de fournir une mise à jour sur l'efficacité de cette cohorte d'expansion au premier semestre 2025. L'HGSOC est particulièrement sensible à l'inhibition du CDK9 en raison d'une amplification ou surexpression de MYC ainsi que de déficiences de recombinaison homologue, touchant une proportion significative des patientes atteintes de cancer de l'ovaire.
Kronos Bio (NASDAQ: KRON) hat den ersten Patienten in einer Erweiterungs-Kohorte seiner klinischen Studie KB-0742 dosiert, die sich auf platin-resistenten hochgradigen serösen Eierstockkrebs (HGSOC) konzentriert. Die Studie verwendet eine 80mg-Dosis bei einem Vier-Tage-behandeln, drei-Tage-pause Schema, das die Dosis-Eskalations-Phase erfolgreich durchlaufen hat. Dieses Dosierungsschema wird voraussichtlich eine 1,8-fache Erhöhung der AUC im Vergleich zum vorherigen 60mg, drei-Tage-behandeln, vier-Tage-pause Schema bieten.
KB-0742 hat ein günstiges Sicherheitsprofil bei über 100 Patienten gezeigt, ohne dass Neutropenie Grad 3 oder 4 beobachtet wurde. Das Unternehmen plant, im ersten Halbjahr 2025 ein Update zur Wirksamkeit dieser Erweiterungs-Kohorte anzubieten. HGSOC ist besonders empfindlich gegenüber CDK9-Inhibition aufgrund von MYC-Amplifikation oder -Überexpression und Defekten der homologen Rekombination, die einen signifikanten Teil der Patientinnen mit Eierstockkrebs betreffen.
- KB-0742 cleared 80mg four-days-on, three-days-off dosing schedule in dose escalation
- Safety database of over 100 patients with no grade 3 or 4 neutropenia observed
- Preliminary anti-tumor activity shown in transcriptionally addicted solid tumors at 60mg dose
- New dosing regimen expected to provide 1.8-fold increase in AUC over seven days
- Prolonged stable disease of over 300 days observed in one platinum-resistant HGSOC patient
- None.
Insights
The initiation of the expansion cohort with KB-0742 in platinum-resistant high-grade serous ovarian cancer (HGSOC) is promising. HGSOC is a challenging cancer type with high unmet medical needs, particularly due to resistance to standard platinum-based therapies. The fact that KB-0742 targets CDK9, which is critical in transcription regulation, gives it a unique mechanism of action that could prove beneficial for patients with MYC amplification or homologous recombination deficiencies (HRD+). The preliminary safety data of over 100 patients without severe neutropenia is encouraging, suggesting that KB-0742 may be well-tolerated while potentially offering significant therapeutic benefits.
The data shared by Kronos Bio regarding the pharmacokinetics of KB-0742 is particularly noteworthy. The 1.8-fold increase in AUC with the 80mg four-days-on, three-days-off schedule compared to the 60mg dose indicates a potentially more effective treatment regimen. This adjustment could lead to better clinical outcomes in terms of tumor reduction and disease stabilization. The promise to provide an efficacy update in the first half of 2025 indicates that there is a clear timeline for prospective data, which will be important for investors and stakeholders monitoring the development of KB-0742.
The announcement of dosing the first patient in this expansion cohort could have a positive impact on Kronos Bio's stock value. The clear path to an efficacy update in 2025 provides a timeline for potential market triggers. Additionally, the focus on a high unmet need area like platinum-resistant HGSOC suggests that if KB-0742 shows positive results, it could capture significant market interest. The clinical progress, combined with the substantial patient population affected by HGSOC and the lack of effective treatments, positions KB-0742 as a valuable asset for Kronos Bio, potentially boosting investor confidence.
— KB-0742 cleared 80mg four-days-on, three-days-off dosing schedule in dose escalation —
— Company expects to provide an efficacy update on this expansion cohort in 1H 2025 —
SAN MATEO, Calif. and CAMBRIDGE, Mass., July 23, 2024 (GLOBE NEWSWIRE) -- Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to developing small molecule therapeutics that address cancers and other diseases driven by deregulated transcription, today announced the first patient dosed in an expansion cohort with KB-0742 at a dose of 80mg given on a four-days-on, three-days-off schedule. This expansion cohort is enrolling platinum-resistant patients with high-grade serous ovarian cancer (HGSOC), a tumor type which is particularly sensitive to CDK9 inhibition due to MYC amplification or overexpression and deficiencies in homologous recombination (HRD+).
“To date, KB-0742 has a safety database of over 100 patients, with no grade 3 or 4 neutropenia observed, and has shown preliminary anti-tumor activity in transcriptionally addicted solid tumors at the 60mg dose given three-days-on, four-days-off,” said Norbert Bischofberger, Ph.D., president and chief executive officer, Kronos Bio, Inc., “Pharmacokinetic modeling of 80mg four-days-on, three-days-off schedule shows a 1.8-fold increase in AUC over seven days relative to the 60mg three-days-on, four-days-off schedule. With this dose and schedule, we believe that KB-0742 will deliver therapeutic responses in this high unmet need population. We look forward to providing an update on the efficacy of KB-0742 in the first half of 2025.”
In the United States there are an estimated 22,000 new cases of ovarian cancer each year, with a five-year survival rate of less than
“We are excited for the focused expansion of KB-0742 in platinum-resistant HGSOC. KB-0742 has to date provided prolonged stable disease of over 300 days in one of my platinum-resistant HGSOC patients,” said Howard “Skip” A. Burris M.D., president of Sarah Cannon Research Institute (SCRI). “HGSOC patients have limited treatment options after progressing on platinum therapy and KB-0742 brings new possibilities to those battling this devastating disease.”
Kronos Bio, Inc (Nasdaq: KRON) is a clinical-stage company dedicated to developing small molecule therapeutics that address deregulated transcription, a hallmark of cancer and other diseases. Our proprietary discovery engine decodes complex transcription factor regulatory networks to identify druggable cofactors. We screen for and optimize small molecules that target these cofactors in a tumor-specific context. These efforts have yielded a preclinical pipeline along with two internally developed drug candidates. KB-0742 targets CDK9 to address MYC deregulation in solid tumors and KB-9558 targets p300 to address IRF4 dependence in multiple myeloma.
Kronos Bio is based in San Mateo, Calif., and has a research facility in Cambridge, Mass. For more information, visit https://www.kronosbio.com/ or follow the Company on LinkedIn.
About KB-0742:
KB-0742 is a selective, oral inhibitor of CDK9, a key cofactor of oncogenic MYC transcription factor activity. KB-0742-1001 (NCT04718675) is a Phase 1/2 open-label dose escalation and cohort expansion study of KB-0742 as a treatment for MYC-amplified and other transcriptionally addicted relapsed or refractory solid tumors. KB-0742 is currently being studied in an expansion cohort focused on platinum-resistant high-grade serous ovarian cancer patients.
Forward-Looking Statements
Statements in this press release that are not statements of historical fact are forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release, in some cases, uses terms such as “anticipate,” “believe,” “could,” “expect,” “plan,” “will,” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding Kronos Bio’s intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, the next expected efficacy update on the expansion cohort in the KB-0742 trial; projections from pharmacokinetic modeling; our belief that KB-0742 will deliver therapeutic responses; estimated patient populations; the potential of Kronos Bio’s product candidates and its proprietary discovery engine; and other statements that are not historical fact. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: changes in the macroeconomic environment or competitive landscape that impact Kronos Bio’s business; whether Kronos Bio will be able to progress its clinical trials on the timelines anticipated, including due to risks inherent in the clinical development of novel therapeutics; risks related to Kronos Bio’s limited experience as a company in conducting clinical trials; the risk that results of preclinical studies, early clinical trials (including preliminary results) and pharmacokinetic modeling are not necessarily predictive of future results; risks associated with enrolling clinical trials; and risks associated with the sufficiency of Kronos Bio’s cash resources and need for additional capital. These and other risks are described in greater detail in Kronos Bio’s filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in its Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, filed with the SEC on May 9, 2024. Any forward-looking statements that are made in this press release speak only as of the date of this press release and are based on management’s assumptions and estimates as of such date. Except as required by law, Kronos Bio assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.
Source: Kronos Bio, Inc.
Investor & Media Contact:
Margaux Bennett
Vice President, Corporate Development and Investor Relations, Kronos Bio, Inc.
650-781-5026
mbennett@kronosbio.com
FAQ
What is the new dosing schedule for KB-0742 in the Kronos Bio expansion cohort?
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