IDEAYA Biosciences Announces Successful FDA Type D Meeting on Phase 3 Registrational Trial Design for Darovasertib as Neoadjuvant Therapy for Primary Uveal Melanoma
IDEAYA Biosciences (NASDAQ:IDYA) has announced a successful FDA Type D meeting regarding the Phase 3 registrational trial design for darovasertib as neoadjuvant therapy for primary uveal melanoma (UM). The company plans to initiate the Phase 3 randomized trial in H1 2025, involving approximately 520 patients randomized 2:1 to treatment versus control.
The trial will include two cohorts: 120 enucleation-eligible UM patients and 400 plaque brachytherapy (PB) eligible patients. For the enucleation cohort, the primary endpoint is eye preservation rate, while the PB cohort's primary endpoint focuses on vision loss measurement. Both cohorts require no detriment to Event-Free-Survival as a secondary endpoint.
Darovasertib, a protein kinase C inhibitor, has received FDA Breakthrough Therapy Designation for neoadjuvant therapy in enucleation-recommended primary UM and Fast Track designation for combination therapy in metastatic UM. The trial will use 300mg BID darovasertib as the move-forward dose.
IDEAYA Biosciences (NASDAQ:IDYA) ha annunciato un incontro di successo con la FDA di Tipo D riguardante il design della sperimentazione registrativa di Fase 3 per darovasertib come terapia neoadiuvante per il melanoma uveale primario (UM). L'azienda prevede di avviare la sperimentazione randomizzata di Fase 3 nel primo semestre del 2025, coinvolgendo circa 520 pazienti randomizzati in un rapporto di 2:1 tra trattamento e controllo.
La sperimentazione includerà due coorti: 120 pazienti con UM idonei all'enucleazione e 400 pazienti idonei alla brachiterapia a placche (PB). Per la coorte di enucleazione, l'endpoint primario è il tasso di conservazione dell'occhio, mentre l'endpoint primario della coorte PB si concentra sulla misurazione della perdita della vista. Entrambe le coorti richiedono che non ci sia alcun danno alla sopravvivenza libera da eventi come endpoint secondario.
Darovasertib, un inibitore della proteina chinasi C, ha ricevuto la Designazione di Terapia Innovativa dalla FDA per la terapia neoadiuvante nei casi di UM primario raccomandati per enucleazione e la Designazione Fast Track per la terapia combinata nell'UM metastatico. La sperimentazione utilizzerà darovasertib a 300 mg BID come dose da proseguire.
IDEAYA Biosciences (NASDAQ:IDYA) ha anunciado una reunión exitosa de Tipo D con la FDA respecto al diseño del ensayo registrativo de Fase 3 para darovasertib como terapia neoadyuvante para el melanoma uveal primario (UM). La compañía planea iniciar el ensayo aleatorizado de Fase 3 en la primera mitad de 2025, involucrando aproximadamente a 520 pacientes aleatorizados en una proporción de 2:1 entre tratamiento y control.
El ensayo incluirá dos cohortes: 120 pacientes con UM elegibles para enucleación y 400 pacientes elegibles para braquiterapia con placas (PB). Para la cohorte de enucleación, el objetivo primario es la tasa de preservación del ojo, mientras que el objetivo primario de la cohorte PB se centra en la medición de la pérdida de visión. Ambas cohortes requieren que no haya detrimento en la Supervivencia Libre de Eventos como objetivo secundario.
Darovasertib, un inhibidor de la proteína quinasa C, ha recibido la Designación de Terapia Innovadora de la FDA para la terapia neoadyuvante en UM primario recomendado para enucleación y la Designación Fast Track para terapia combinada en UM metastático. El ensayo utilizará darovasertib a 300 mg BID como la dosis a seguir.
IDEAYA 바이오사이언스(NASDAQ:IDYA)는 기본 유리멜라노마(UM)에 대한 신보조요법으로 다로바세르티브의 3상 등록 시험 설계에 관한 성공적인 FDA D형 회의를 발표했습니다. 이 회사는 2025년 상반기에 약 520명의 환자를 무작위로 2:1 비율로 치료군과 대조군에 배정하여 3상 무작위 시험을 시작할 계획입니다.
시험은 두 개의 집단을 포함합니다: 120명의 유리멜라노마 환자와 400명의 플라크 브라키치료(PB) 적격 환자. 유리멜라노마 집단의 주요 목표는 눈 보존율이며, PB 집단의 주요 목표는 시력 손실 측정에 중점을 둡니다. 두 집단 모두 사건 발생 없는 생존율(Event-Free Survival)에 대한 손상이 없어야 합니다.
다로바세르티브는 단백질 키나제 C 억제제로, 유리멜라노마에 대한 신보조요법으로 FDA 혁신 치료 지정(Breakthrough Therapy Designation)과 전이성 유리멜라노마에 대한 병용 치료로 신속 심사(Fast Track) 지정을 받았습니다. 이 시험에서는 300mg BID의 다로바세르티브를 진행할 용량으로 사용할 예정입니다.
IDEAYA Biosciences (NASDAQ:IDYA) a annoncé une réunion réussie de type D avec la FDA concernant la conception de l'essai d'enregistrement de phase 3 pour le darovasertib en tant que thérapie néoadjuvante pour le mélanome uvéal primaire (UM). L'entreprise prévoit de lancer l'essai randomisé de phase 3 au premier semestre 2025, impliquant environ 520 patients randomisés dans un rapport de 2:1 entre traitement et contrôle.
L'essai comprendra deux cohortes : 120 patients UM éligibles à l'enucleation et 400 patients éligibles à la brachythérapie à plaques (PB). Pour la cohorte d'enucleation, le critère principal est le taux de conservation de l'œil, tandis que le critère principal de la cohorte PB se concentre sur la mesure de la perte de vision. Les deux cohortes exigent qu'il n'y ait aucun préjudice à la survie sans événement en tant que critère secondaire.
Le darovasertib, un inhibiteur de la protéine kinase C, a reçu la désignation de thérapie innovante de la FDA pour la thérapie néoadjuvante dans les cas de mélanome primaire recommandés pour l'enucleation et la désignation Fast Track pour la thérapie combinée dans le mélanome métastatique. L'essai utilisera 300 mg BID de darovasertib comme dose à suivre.
IDEAYA Biosciences (NASDAQ:IDYA) hat ein erfolgreiches FDA-Typ-D-Meeting bezüglich des Designs der registrierenden Phase-3-Studie für Darovasertib als neoadjuvante Therapie für primäres uveales Melanom (UM) angekündigt. Das Unternehmen plant, die randomisierte Phase-3-Studie im ersten Halbjahr 2025 zu beginnen, wobei etwa 520 Patienten im Verhältnis 2:1 für Behandlung und Kontrolle randomisiert werden.
Die Studie wird zwei Kohorten umfassen: 120 UM-Patienten, die für eine Enukleation geeignet sind, und 400 Patienten, die für die Plaque-Brachytherapie (PB) geeignet sind. Für die Enukleationskohorte ist der primäre Endpunkt die Augenbewahrungsrate, während der primäre Endpunkt der PB-Kohorte sich auf die Messung des Sehverlusts konzentriert. Beide Kohorten erfordern, dass es keinen Nachteil für die ereignisfreie Überlebensrate als sekundären Endpunkt gibt.
Darovasertib, ein Hemmer der Proteinkinase C, hat von der FDA die Breakthrough-Therapy-Designierung für die neoadjuvante Therapie bei primärem UM, das zur Enukleation empfohlen wird, und die Fast-Track-Designierung für die Kombinationstherapie bei metastatischem UM erhalten. Die Studie wird 300 mg BID Darovasertib als die weiterverwendete Dosis verwenden.
- FDA Breakthrough Therapy Designation received for darovasertib
- Successful FDA Type D meeting confirming registrational trial design
- Potential for early regulatory submission of enucleation cohort data
- Clear regulatory pathway established with defined endpoints
- Phase 3 trial initiation not until H1 2025
- Large patient enrollment required (520 patients) may extend trial timeline
- Multiple cohorts and endpoints increase trial complexity
Insights
IDEAYA's successful FDA Type D meeting represents a significant regulatory milestone for darovasertib's development path. The FDA's acceptance of eye preservation rate and proportion of patients with vision loss as primary endpoints, rather than requiring survival improvement, substantially de-risks the approval pathway for this uveal melanoma treatment.
The agency's agreement to these endpoints reflects recognition of the urgent unmet need in this patient population, where current treatment options are and often result in vision loss or complete eye removal. What's particularly notable is the FDA's acceptance of a non-inferiority requirement for Event-Free-Survival as a secondary endpoint ("no detriment" with overlapping confidence intervals), rather than demanding superiority.
The Breakthrough Therapy Designation previously granted provides significant regulatory advantages including intensive FDA guidance and potential for priority review. This, combined with the established trial design clarity, creates a well-defined path to market. The potential for sequential submissions - with the enucleation cohort data potentially submitted before the plaque brachytherapy cohort - could accelerate commercialization timelines.
With a clear regulatory strategy now established and endpoints that don't require demonstrating survival advantages, IDEAYA has dramatically improved its probability of technical and regulatory success for darovasertib in primary uveal melanoma.
Darovasertib's development pathway represents a potentially transformative approach to primary uveal melanoma (UM) treatment. The neoadjuvant strategy - administering therapy before standard interventions like enucleation or plaque brachytherapy - addresses a critical therapeutic gap in UM management.
The clinical endpoints chosen are particularly patient-centered and meaningful. For enucleation patients, the eye preservation rate endpoint directly addresses the most devastating outcome of UM - complete eye removal. For plaque brachytherapy patients, measuring vision preservation (preventing >15-letter ETDRS BCVA loss) targets maintaining functional vision, a key quality-of-life metric.
The drug's mechanism as a protein kinase C (PKC) inhibitor is scientifically sound for UM, where PKC signaling drives tumor growth. The 300mg BID dosing confirms an acceptable safety profile at therapeutic levels. Most compelling is the existing clinical efficacy evidence cited - promising results in over 90 neoadjuvant patients that likely supported the breakthrough designation.
With dual cohorts totaling 520 patients and 2:1 randomization, the trial is robustly powered. The potential for sequential cohort submissions creates multiple near-term value inflection points while addressing both patient populations with distinct treatment needs. This comprehensive approach to primary UM makes darovasertib a potential standard-of-care intervention for this rare but devastating ocular cancer.
- Targeting to initiate Phase 3 randomized registrational trial for darovasertib in the neoadjuvant setting in primary UM in H1 2025
- Clinical endpoints supportive of full approval based on FDA Type D Meeting: Eye preservation rate as the primary endpoint for enucleation patients. Proportion of patients with best corrected visual acuity 15-letter loss from time of randomization and time of completion of plaque brachytherapy (PB) as the primary endpoint for PB patients. No detriment to Event-Free-Survival (EFS) is required for both cohorts as a secondary endpoint
- We project registrational trial enrollment for the enucleation cohort will be 120 patients and 400 patients for the plaque brachytherapy cohort with a 2:1 randomization
- Potential to submit the enucleation cohort data for regulatory review earlier than the PB cohort pending the EFS data maturity in both cohorts
"The successful FDA Type D meeting provides darovasertib a registrational path as neoadjuvant therapy for UM, using primary clinical endpoints of eye preservation and proportion of patients with vision loss, with no detriment to EFS as a secondary endpoint required for both cohorts. Based on the promising clinical efficacy and safety observed with darovasertib in the neoadjuvant setting in over 90 patients and the recent Breakthrough Therapy Designation by the US FDA, we are excited to advance the darovasertib program into our second registrational trial," said Dr. Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.
Darovasertib is a potent and selective protein kinase C (PKC) inhibitor being developed to broadly address primary and metastatic UM (MUM). Darovasertib has received
FDA Guidance from the Type D Meeting on the Phase 3 Neoadjuvant Darovasertib Registrational Trial Design for Potential Regulatory Approval in Primary UM
IDEAYA is targeting to initiate the Phase 3 randomized clinical trial evaluating neoadjuvant darovasertib in primary UM in the first half of 2025. The randomized Phase 3 clinical trial design incorporates guidance and feedback from the
In the Phase 3 clinical trial, we currently project approximately 520 patients will be randomized 2:1 to the darovasertib treatment versus control arm. There will be 2 cohorts enrolled: 1) 120 enucleation eligible UM patients, 2) 400 PB eligible UM patients. For the enucleation cohort, the randomization will be with or without darovasertib as neoadjuvant therapy. For the PB cohort, the randomization will be darovasertib followed by PB versus PB alone.
Key highlights of the Phase 3 registrational trial design in neoadjuvant UM, based on FDA guidance:
- Eye preservation rate (exceed lower bound of
10% eye preservation rate with a95% confidence interval) is the primary endpoint for the enucleation UM cohort - Proportion of patients with vision loss from the time of randomization and time of completion of PB is the primary endpoint for the plaque brachytherapy cohort. Vision detriment will be measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA) of >15-letters lost
- No detriment to Event-Free-Survival (EFS) is a secondary endpoint for both cohorts and is required for approval. No detriment is defined as overlapping confidence intervals
- Additional secondary endpoints: Overall Response Rate (>
20% ocular tumor shrinkage by product of diameters), proportion of patients with clinically significant macular edema, proportion of subjects with 20/200 vision loss or worse (legal blindness), proportion of subjects with reduction of radiation dose of >20% delivered to key eye structures - Potential to submit the enucleation cohort data for regulatory review earlier than the PB cohort pending the EFS data maturity in both cohorts
- 300mg BID darovasertib will be the move-forward dose for the registrational trial
About IDEAYA Biosciences
IDEAYA is a precision medicine oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. IDEAYA's approach integrates capabilities in identifying and validating translational biomarkers with drug discovery to select patient populations most likely to benefit from its targeted therapies. IDEAYA is applying its research and drug discovery capabilities to synthetic lethality – which represents an emerging class of precision medicine targets.
Forward-Looking Statements
This press release contains forward-looking statements, including, but not limited to, statements related to: (i) the potential regulatory approval of darovasertib as neoadjuvant therapy for primary UM; (ii) the potential therapeutic benefit, including safety and efficacy, of darovasertib; and (iii) the design and timing of the Phase 3 clinical trial of darovasertib for neoadjuvant for primary UM. Such forward-looking statements involve substantial risks and uncertainties that could cause IDEAYA's preclinical and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including IDEAYA's programs' early stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, IDEAYA's ability to successfully establish, protect and defend its intellectual property, and other matters that could affect the sufficiency of existing cash to fund operations. IDEAYA undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of IDEAYA in general, see IDEAYA's Annual Report on Form 10-K dated February 20, 2024 and any current and periodic reports filed with the
Investor and Media Contact
IDEAYA Biosciences
Andres Ruiz Briseno
Chief Accounting Officer
investor@ideayabio.com
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