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 02B - MK-3475-02B (KEYMAKER-U02)

Studio Clinico

Patologia: Melanoma

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: 1, II Randomizzato

Linee di trattamento: Prima linea

Criteri di inclusione: 

• Have histologically or cytologically confirmed melanoma
• Unresectable Stage III or Stage IV melanoma
• At least one measurable lesion by CT or MRI per RECIST 1.1 as confirmed by BICR.
• Has been untreated for advanced disease except:
  
  • BRAF V600 mutation-positive melanoma may have received SOC targeted therapy as 1L therapy for advanced disease (eg, BRAF/MEK inhibitor, alone or in combination).
    Note: Prior 1L therapy for advanced disease with targeted therapy is permitted if it was completed at least 4 weeks before randomization, disease progression has been documented radiologically and all related AEs have either returned to baseline or stabilized.
  • Prior adjuvant or neoadjuvant therapy, with targeted therapy or immunotherapy (such as anti-PD-1 therapy, anti-CTLA-4 or Interferon) is permitted. Prior anti‑PD‑1 therapy will only be permitted if relapse did not occur during treatment or within 6 months of treatment discontinuation. No other prior adjuvant or neoadjuvant therapy will be allowed. Note: Both prior adjuvant or neoadjuvant and 1L therapy for advanced disease with targeted therapy (eg, BRAF/MEK inhibitor, alone or in combination) is not allowed.
• Documentation of BRAF V600-activating mutation status or consent to BRAF V600 mutation testing during Screening (participants with BRAF mutation-positive melanoma as well as BRAF wild-type or unknown are eligible).

Criteri di esclusione: 

• Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy
• Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has ocular or mucosal melanoma
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has known history of hepatitis B (defined as HBsAg reactive) or known hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
• Has received prior radiotherapy within 2 weeks of the first dose of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.

Trattamento sperimentale: 

A) Pembrolizumab + Vibostolimab
B) Coformulation Pembrolizumab/Quavonlimab
C) Coformulation Pembrolizumab/Quavonlimab + Lenvatinib

Trattamento di controllo: 

A) Pembrolizumab

Obiettivi primari dello studio: 

The goal of substudy 02B is to evaluate the safety and efficacy of investigational treatment arms in participants with 1L advanced melanoma and to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/pembrolizumab monotherapy.

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2019-003977-24

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