R3767-ONC-2011 - A Phase 2 and Phase 3 Trial of Fianlimab (REGN3767, Anti-LAG-3) + Cemiplimab Versus Pembrolizumab in Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma.

Studio Clinico

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: 

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Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2021-004453-23 - NCT05352672

Data di inserimento: 11.04.2024

Promotore

Regeneron Pharmaceuticals

Principal Investigator ITALIA

Riferimento: Dr. Info non disponibile

Telefono: 00000

Email: nd@nd.it

Localita: nd