Patologia: Melanoma
Osservazionale-Sperimentale: Sperimentale
Monocentrico-Multicentrico: Multicentrico
Randomizzato: Sì
Fase di studio: II, III
Linee di trattamento: Prima linea
Criteri di inclusione:
1- Age ≥12 years on the date of providing informed consent
2- Patients with histologically confirmed unresectable Stage III and Stage IV (metastatic) melanoma (AJCC, 8th revised edition) who have not received prior systemic therapy for advanced unresectable disease
- Patients who received adjuvant and/or neoadjuvant systemic therapies are eligible if they did not have evidence of progression or recurrence of disease and/or discontinued due to occurrence of unmanageable imAEs ≥ grade 3 (with the exclusion of endocrinopathies which are fully controlled by hormone replacement) while on such therapies. Also, patients must have had a treatment-free and disease-free interval of >6 months. Accrual of these patients is limited to approximately 10% of the total population enrolled in each of the Phase 2 and Phase 3 parts of the study.
- Patients with acral and mucosal melanomas are eligible. Combined accrual will be limited to 10% of the total population enrolled in the Phase 3 part of the study.
3- Measurable disease per RECIST v1.1
- Previously irradiated lesions can only be counted as target lesions if they have been demonstrated to progress and no other target lesion is available
- Cutaneous lesions should be evaluated as non-target lesions
4- Performance status:
- For adult patients: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- For pediatric patients: Karnofsky performance status ≥70 (patients ≥16 years) or Lansky performance status ≥70 (patients ≤16 years)
5- Anticipated life expectancy of at least 3 months.
Criteri di esclusione:
1- Uveal melanoma
2- Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents. The following are non-exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment.
3- Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C virus (HCV) infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection
4- Unknown v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation status as described in the protocol
5- Systemic immune suppression:
- Use of immunosuppressive doses of corticosteroids (>10mg of prednisone per day or equivalent) within 14 days of the first dose of study medication. Physiologic replacement doses are allowed up to and including 10mg of prednisone/day or equivalent. Inhaled or topical steroids are permitted, if they are not for treatment of an autoimmune disorder.
- Other clinically relevant forms of systemic immune suppression
6- Treatment with other anti-cancer therapy including immuno- therapy, chemotherapy, major surgery or biological therapy within 21 days prior to the first dose of trial treatment. Adjuvant hormonotherapy used for breast cancer or other hormone-sensitive cancers in long term remission is allowed.
7- History or current evidence of significant (CTCAE Grade ≥2) local or systemic infection (e. g., cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 14 days prior to the first dose of trial medication.
8- Participants with a history of myocarditis.
9- Active or untreated brain metastases or spinal cord compression. Patients with leptomeningeal disease are excluded. Patients with known brain metastases are eligible if they:
- Received radiotherapy or another appropriate standard therapy for the brain metastases,
- Have neurologically returned to baseline (except for residual signs and symptoms related to the CNS treatment) for at least 14 days prior to enrollment
- Did not require immunosuppressive doses of corticosteroids therapy (>10mg of prednisone per day or equivalent) in the 14 days prior to enrollment
- Are asymptomatic with a single untreated brain metastasis <10 mm in size
Note: Other protocol-defined Inclusion/ Exclusion criteria apply.
Trattamento sperimentale:
A: fianlimab+cemiplimab
dose 1
Phase 2 and Phase 3
A1: fianlimab+cemiplimab
dose 2
Phase 2 and Phase 3 (except for PA1 patients as described in the protocol)
B: pembrolizumab+placebo
Phase 2 and Phase 3
C: cemiplimab+placebo
Phase 2 (as described in the protocol).
Trattamento di controllo:
-
ASST Spedali Civili di Brescia
Piazzale Spedali Civili 1 - 25123 Brescia - BS
Azienda Ospedaliera S. Croce e Carle di Cuneo
Via Michele Coppino 26 - 12100 Cuneo - CN
IRCCS A.O.U. San Martino - IST
Largo Rosanna Benzi 10 - 16132 Genova - GE
A.O. San Gerardo
Via Pergolesi 33 - 20900 Monza - MB
A.O.U. Maggiore della Carità
Corso Mazzini 18 - 28100 Novara - NO
SCDU di Oncologia
Istituto Oncologico Veneto IRCCS
Via Gattamelata 64 - 35128 Padova - PD
IRCCS Candiolo (TO)
St.Provinciale Km 3,95 SP142 - 10060 Candiolo - TO
AOU Città della Salute e della Scienza di Torino
Corso Bramante 88 - 10126 Torino - TO
Presidio ospedaliero di Santa Chiara
Largo Medaglie d'Oro 1 - 38122 Trento - TN
Azienda Ospedaliera Santa Maria della Misericordia
Piazzale Santa Maria della Misericordia 15 - 33100 Udine - UD
Azienda Sanitaria Universitaria Friuli Centrale (ASU FC)
AOU Pisana - Santa Chiara
Via Roma 67 - 56126 Pisa - PI
Istituto Toscano Tumorio Polo Oncologico
Istituto Dermopatico dell'Immacolata
Via Monti di Creta 104 - 00167 Roma - RM
Università Campus Bio-medico
Via Álvaro del Portillo 200 - 00128 Roma - RM
AO S. Maria Terni
Via Tristano di Joannuccio 1 - 05100 Terni - TR
Istituto Tumori “Giovanni Paolo II” IRCCS
Viale Orazio Flacco 65 - 70124 Bari - BA
IRCCS Ospedale Casa Sollievo della Sofferenza
Viale Cappuccini 1 - 71013 San Giovanni Rotondo - FG
AOU degli studi della Campania Luigi Vanvitelli
Piazza Luigi Miraglia 2 - 80138 Napoli - NA
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Via Mariano Semmola - 80131 Napoli - NA
Numero di iscrizione a registro: 2021-004453-23 - NCT05352672
Data di inserimento: 11.04.2024
Regeneron Pharmaceuticals
Riferimento: Dr. Info non disponibile
Telefono: 00000
Email: nd@nd.it
Localita: nd