Patologia: Melanoma
Osservazionale-Sperimentale: Sperimentale
Monocentrico-Multicentrico: Multicentrico
Randomizzato: Sì
Fase di studio: II Randomizzato
Richiesta mandatoria di tessuto: Sì
Linee di trattamento: Non applicabile
Criteri di inclusione:
- Male or female participants ≥18 years of age at the time of informed consent.
Histologically confirmed unresectable (Stage IIIB, IIIC, or IIID) or metastatic (Stage IV) cutaneous melanoma, according to the AJCC 8th edition.
- Documented evidence of a BRAF V600E or V600K mutation.
- Submission of adequate tumor tissue for central laboratory testing of BRAF V600E-mutation and biomarkers is required for all participants during the screening period and prior to randomization.
- Must have received only 1 prior line of systemic therapy for melanoma (either adjuvant therapy or first-line anti-PD-1 monotherapy (ie, nivolumab or pembrolizumab)
- Must have anti-PD-1 resistant disease (primary or secondary) with confirmed disease progression per RECIST v1.1 either during or after receipt of an approved anti-PD-1 monotherapy (ie, nivolumab or pembrolizumab) for melanoma, defined according to the SITC Immunotherapy Resistance Taskforce (Kluger et al, 2020).
- Have at least one measurable lesion per RECIST v1.1.
- ECOG PS of 0-1, and adequate organ and cardiac function, including LVEF ≥50% by cardiac imaging.
Criteri di esclusione:
- Mucosal or ocular melanoma.
- Diagnosis of immunodeficiency or an active autoimmune disease that required systemic treatment with chronic systemic steroid therapy or any other form of immunosuppressive therapy within the past 2 years.
- Clinically significant cardiovascular diseases.
- History of thromboembolic or cerebrovascular events ≤12 weeks prior to randomization.
- History or current evidence of RVO or current risk factors for RVO.
- Concurrent neuromuscular disorder that is associated with the potential of elevated CK.
- Active bacterial, fungal, or viral infection requiring systemic therapeutic treatment within 2 weeks prior to randomization.
- Current non-infectious pneumonitis/interstitial lung disease or history of noninfectious pneumonitis/interstitial lung disease requiring steroids.
- Prior or current symptomatic brain metastasis, leptomeningeal disease or other active CNS metastases.
- Participants who permanently discontinued prior anti-PD-1 therapy due to toxicity or will be unable to tolerate combination therapy based on investigator judgement are excluded.
- Prior treatment with ipilimumab; prior combined immunotherapy blockade with anti-PD-1/L-1; prior treatment with a BRAFi and/or MEKi; or previous administration of an investigational anti-cancer agent for the adjuvant or first-line treatment of melanoma prior to randomization.
Numero di pazienti previsti:
25
Schema di trattamento:
Experimental: Triplet
encorafenib and binimetinib in combination with pembrolizumab
Active Comparator: Doublet
ipilimumab and nivolumab.
Trattamento sperimentale:
encorafenib + binimetinib + pembrolizumab
Trattamento di controllo:
ipilimumab + nivolumab
Obiettivi primari dello studio:
Objective Response Rate (ORR) is defined as the proportion of participants in each treatment arm with a confirmed best overall response of either Complete Response (CR) or Partial Response (PR), as determined by investigator assessment per RECIST v1.1 [Time Frame: Time from the date of randomization to the earliest date disease progression, or start of subsequent anticancer therapy, or death due to any cause (assessed up to approximately 48 months).]
Data di inizio dell'arruolamento: 30.06.2023
Data di fine dell'arruolamento: 08.10.2024
IRCCS A.O.U. San Martino - IST
Largo Rosanna Benzi 10 - 16132 Genova - GE
Riferimento: Dr. Francesco Spagnolo
Email: francesco.spagnolo@hsanmartino.it
Istituto Europeo di Oncologia
Via Ripamonti 435 - 20141 Milano - MI
Riferimento: Dr.ssa Paola Queirolo
Telefono: 0257489459
Email: Paola.queirolo@ieo.it
Istituto Oncologico Veneto IRCCS
Via Gattamelata 64 - 35128 Padova - PD
NB: Arruolamento pazienti non ancora attivo
Riferimento: Dr.ssa Vanna Chiarion-Sileni
Telefono: 3401981329
Email: vanna.chiarion@iov.veneto.it
IRCCS Candiolo (TO)
St.Provinciale Km 3,95 SP142 - 10060 Candiolo - TO
Azienda Ospedaliera di Perugia
Via Dottori 1 - 06132 Perugia - PG
Santa Maria della Misericordia
Riferimento: Prof. Mario Mandalà
Telefono: 0755784188
Email: mario.mandala@unipg.it
Istituto Nazionale Tumori “Regina Elena”
Via Elio Chianesi 53 - 00144 Roma - RM
NB: Arruolamento pazienti non ancora attivo
Azienda Ospedaliera Universitaria Senese
Viale Bracci 16 - 53100 Siena - SI
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Via Mariano Semmola - 80131 Napoli - NA
Riferimento: Dr.ssa Ester Simeone
Telefono: 08117770387
Email: e.simeone@istitutotumori.na.it
AOU Policlinico Paolo Giaccone
Via del Vespro 129 - 90127 Palermo - PA
Riferimento: Dr.ssa Gaetana Rinaldi
Telefono: 0916554411
Email: rinaldiambulatorio@gmail.com
Numero di iscrizione a registro: 2021-003640-24
Data di inserimento: 05.10.2023
Pfizer
Parexel
Riferimento: Dr. Info non applicabile (nuovo regolamento Europeo)
Telefono: 00000
Email: na@na.it
Localita: na