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

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: Adiuvante/neoadiuvante

Criteri di inclusione: 

- Has histologically or cytologically confirmed melanoma
- Has clinically detectable and resectable Stage IIIB or IIIC or IIID melanoma amenable to surgery
- Has been untreated for Stage IIIB, IIIC or IIID melanoma
    - surgical resection of primary melanoma is allowed
    - prior radiotherapy to the primary melanoma is allowed
- Has provided a baseline tumor biopsy
- Male participants who receive V937 are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 120 days after the last dose of V937
- Female participants 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-7684, V937, 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 monoclonal antibody (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 only mucosal lesions
- Is not naïve to Talimogene laherparepvec (TVEC) and other oncolytic viruses

Trattamento sperimentale: 

- Pembrolizumab + MK-7684
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab intravenously (IV) plus MK-7684 IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

- Pembrolizumab + V937
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus V937 intratumorally (IT) at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

- Pembrolizumab
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

Trattamento di controllo: 

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Obiettivi primari dello studio: 

The goal of substudy 02C is to evaluate the safety and efficacy of investigational treatment arms in participants with Stage III melanoma who are candidates for neoadjuvant therapy 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

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2019-003978-22 - NCT04303169

Data di inserimento: 14.07.2021

Data di aggiornamento: 13.05.2022

Promotore

Merck Sharp & Dohme Corp.

Principal Investigator ITALIA

Istituto Europeo di Oncologia (IEO) - Divisione Sviluppo Nuovi Farmaci per Terapie Innovative

Riferimento: Prof. Giuseppe Curigliano

Telefono: 0257489599

Email: giuseppe.curigliano@ieo.it

Localita: Milano