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 02A - MK-3475-02A

Studio Clinico

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.

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2019-003956-35 - NCT04305041

Data di inserimento: 14.07.2021

Data di aggiornamento: 13.05.2022

Promotore

Merck Sharp & Dohme Corp.

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