Resumen

Este estudio investiga un fármaco experimental llamado REGN3767, también conocido como fianlimab (R3767), en combinación con otro medicamento llamado REGN2810, también conocido como cemiplimab (cada uno denominado individualmente «fármaco del estudio» o «fármacos del estudio» en combinación). El estudio está orientado a pacientes con un tipo de cáncer de piel conocido como melanoma. Los objetivos del estudio son evaluar la eficacia de la combinación de fianlimab y cemiplimab en el tratamiento del melanoma, en comparación con pembrolizumab, un medicamento aprobado para el tratamiento del melanoma en adultos, y observar similitudes o diferencias en el modo de acción de los fármacos del estudio en participantes adolescentes en comparación con participantes adultos. El estudio aborda otras preguntas de investigación, entre ellas: * Qué efectos adversos pueden producirse al recibir los fármacos del estudio. * Cuánto fármaco del estudio hay en sangre en distintos momentos. * Si el organismo produce anticuerpos contra los fármacos del estudio (lo que podría reducir su eficacia o generar efectos adversos). Los anticuerpos son proteínas presentes naturalmente en el torrente sanguíneo que combaten las infecciones. * Cómo la administración de los fármacos del estudio puede mejorar la calidad de vida.

Elegibilidad

Edad mínima: 12 YearsSexo: ALL

Criterios de inclusión

Age ≥12 years on the date of providing informed consent
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.
Patients with acral and mucosal melanomas are eligible. Accrual will be limited to 10% of the total population.
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
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)
Anticipated life expectancy of at least 3 months

Criterios de exclusión

Uveal melanoma
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.
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
Unknown BRAF V600 mutation status as described in the protocol
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
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.
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.
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
Participants with a history of myocarditis.

Ubicaciones

DIABAID - Instituto de Asistencia Integral en Diabetes

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Centro Medico Austral

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Centro de Investigacion Pergamino

Pergamino, Buenos Aires, Argentina

Instituto de Oncologia de Rosario

Rosario, Santa Fe Province, Argentina

Centro de Investigaciones Medicas y Desarrollo LC S.R.L. (LC Investigacion)

Buenos Aires, Argentina

Exelsus

San Miguel de Tucumán, Argentina

Ensayo de fase 3 de fianlimab (REGN3767, anti-LAG-3) + cemiplimab versus pembrolizumab en pacientes con melanoma localmente avanzado irresecable o metastásico no tratado previamente

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Fianlimab

Cemiplimab

Pembrolizumab

Placebo