A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma: Substudy 02D - MK-3475-02D (KEYMAKER-U02)

Studio Clinico

Patologia: Melanoma

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: 1, II Randomizzato

Richiesta mandatoria di tessuto: Sì

Linee di trattamento: Terza/N linea

Criteri di inclusione: 

• AJCC Stage IV (any T, any N, M1D) melanoma
• At least 1 and no more than 5 measurable brain metastasis disease
• ≥10 mm and ≤30 mm, prior SRT in ≤3 MBM, history of excision ≤2 MBM
• Submission of tumor tissue at enrollment.
  Note: Adequacy confirmation from Central Laboratory Vendor is not required for randomization
• Neurologically asymptomatic from brain metastases
• Not have required or received systemic corticosteroid therapy in the 10 days prior to beginning study intervention
• Able to undergo MRI with Gadolinium contrast agent

Criteri di esclusione: 

• No more than 3 lines of therapy for their metastatic melanoma, inclusive of an adjuvant therapy regimen
• Previous treatment for unresectable or metastatic disease allowed
• Approved adjuvant regimens, IFN-α, anti-PD-1/PD-L1, anti-CTLA-4, and approved molecularly target agents.
• Steroids for physiological replacement are allowed
• Participants who have received anti-PD-1/PD-L1 therapy must have received at least 2 prior doses of an anti-PD-1/L1 mAb
• Participants with prior BRAF inhibitor treatment
• Intracranial disease progression must be demonstrated compared with the nadir of intracranial response during BRAF inhibitor treatment and confirmed with a second MRI brain scan after the drug washout period ±3 days.
• Pre-study images that are of diagnostic quality from at least 3 dates
• Confirmation of progression by repeat MRI may not be necessary for new lesions on BRAF inhibitor

Trattamento sperimentale: 

• Coformulation Pembrolizumab/Quavonlimab + Lenvatinib
• Pembrolizumab + Lenvatinib

Trattamento di controllo: 

NA

Obiettivi primari dello studio: 

The goal of substudy 02D is to evaluate the safety and efficacy of investigational treatment arms in programmed cell-death 1 (PD-1) naïve or PD-1 exposed participants with melanoma brain metastasis (MBM) and to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2020-003742-36

Data di inserimento: 24.05.2022

Promotore

Merck Sharp & Dohme LLC

Principal Investigator ITALIA

Istituto Europeo di Oncologia, Milano - Divisione Sviluppo di Nuovi Farmaci per Terapie Innovative

Riferimento: Prof. Giuseppe Curigliano

Telefono: 0257489599

Email: giuseppe.curigliano@ieo.it

Localita: Milano