Patologia: Melanoma
Osservazionale-Sperimentale: Sperimentale
Monocentrico-Multicentrico: Multicentrico
Randomizzato: Sì
Fase di studio: 1, II
Richiesta mandatoria di tessuto: Sì
Linee di trattamento: Seconda linea, Terza/N linea
Criteri di inclusione:
- Has histologically or cytologically confirmed melanoma
- Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy
- Has progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other therapies
- Has submitted prestudy imaging
- Has not received more than 3 lines of therapy for their advanced melanoma
- Has provided a tumor biopsy
- Male participants who receive lenvatinib are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 5 days after the last dose of lenvatinib; for male participants who only receive pembrolizumab, MK-1308, MK-7684, or a combination, no contraception measures are needed
- Female participant are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) OR use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after the last dose of pembrolizumab, MK-1308, MK-7684 or 30 days after the last dose of lenvatinib, whichever occurs last
- Has adequate organ function
- Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia)
Criteri di esclusione:
- Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days before the first dose of study intervention
- 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 known hypersensitivity including previous clinically significant hypersensitivity reaction to treatment with another mAb
- Has an active autoimmune disease that has required systemic treatment in the past 2 years
- Has an active infection requiring systemic therapy
- Has known history of human immunodeficiency virus (HIV)
- Has known history of hepatitis B
- Has a history of (noninfectious) pneumonitis
- Has a history of active tuberculosis (TB)
- Has received prior systemic anticancer therapy within 4 weeks prior to randomization
- Has received prior radiotherapy within 2 weeks of first dose of study intervention
- Has had major surgery <3 weeks prior to first dose of study intervention
- Has received a live vaccine within 30 days before the first dose of study intervention
- Has participated in a study of an investigational agent within 4 weeks prior to the first dose of study intervention
- Has had an allogeneic tissue/solid organ transplant
- Has a pre-existing Grade ≥3 gastrointestinal fistula or nongastrointestinal fistula
- Has radiographic evidence of encasement of invasion of major blood vessel or of intratumoral cavitation
- Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study intervention
- Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
Trattamento sperimentale:
Pembrolizumab + MK-1308 + MK-7684
Participants will receive pembrolizumab intravenously (IV) plus MK-1308 IV plus MK-7684 IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.
Pembrolizumab + MK-1308 + Lenvatinib
Participants will receive pembrolizumab IV plus MK-1308 IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
Trattamento di controllo:
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Obiettivi primari dello studio:
The goal of substudy 02A is to evaluate the safety and efficacy of investigational treatment arms in participants with PD-1 refractory melanoma to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.
IRCCS Istituto Nazionale dei Tumori
Via Venezian 1 - 20133 Milano - MI
Istituto Europeo di Oncologia
Via Ripamonti 435 - 20141 Milano - MI
Riferimento: Prof. Giuseppe Curigliano
Telefono: 0257489599
Email: giuseppe.curigliano@ieo.it
Istituto Oncologico Veneto IRCCS
Via Gattamelata 64 - 35128 Padova - PD
Riferimento: Dr. Jacopo Pigozzo
Telefono: 0498215931
Email: oncologia.melanoma@iov.veneto.it
Azienda Ospedaliera Universitaria Senese
Viale Bracci 16 - 53100 Siena - SI
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Via Mariano Semmola - 80131 Napoli - NA
Riferimento: Dr. Paolo Ascierto
Telefono: 0815903236
Email: p.ascierto@istitutotumori.na.it
Numero di iscrizione a registro: 2019-003956-35 - NCT04305041
Data di inserimento: 14.07.2021
Data di aggiornamento: 13.05.2022
Merck Sharp & Dohme Corp.
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