Estudio de fase II, aleatorizado, abierto, con múltiples brazos y dos partes, para evaluar la eficacia y seguridad de múltiples combinaciones de LXH254 en pacientes con melanoma con mutación BRAFV600 o NRAS irresecable o metastásico previamente tratado

Activo, no reclutaFase 2ClinicalTrials.gov

ID: NCT04417621Tipo: INTERVENTIONALInicio: 30 de oct de 2020Fin estimado: 2 de feb de 2027

Resumen

El objetivo principal de este estudio es evaluar la eficacia de las combinaciones de LXH254 en melanoma irresecable o metastásico previamente tratado.

Elegibilidad

Edad mínima: 12 YearsEdad máxima: 120 YearsSexo: ALL

Criterios de inclusión

Male or female must be ≥ 12 years For adolescents only (12-17 years): body weight \> 40kg Histologically confirmed unresectable or metastatic cutaneous melanoma
Previously treated for unresectable or metastatic melanoma:
Participants with NRAS mutation:
Participants must have received prior systemic therapy for unresectable or metastatic melanoma with checkpoint inhibitors (CPI), either an anti-PD-1/PD-L1 as a single agent or in combination with anti-CTLA-4, investigational agents, chemotherapy or locally directed anti-neoplastic agents.
A maximum of two prior lines of systemic CPI-containing immunotherapy for unresectable or metastatic melanoma are allowed. Additional agents administered with CPI are permitted.
To rule out pseudo-progression, participants must have documented confirmed progressive disease as per RECIST v1.1 while on/after treatment with checkpoint inhibitor therapy. Confirmation is not required for patients who remained on treatment for \>6 months.
Participants with BRAFV600 mutant disease:
Participants must have received prior systemic therapy for unresectable or metastatic melanoma with checkpoint inhibitors (CPI), either an anti-PD-1/PD-L1 as a single agent or in combination with anti-CTLA-4, investigational agents, chemotherapy or locally directed anti-neoplastic agents. Additionally, participants must have received targeted therapy with a RAFi as a single agent or in combination with a MEKi (+/- CPI allowed) as the last prior therapy.
A maximum of two prior lines of systemic CPI-containing immunotherapy for unresectable or metastatic melanoma are allowed. Additional agents with CPI are permitted.
A maximum of one line of targeted therapy is allowed, and it must be the most recent line of therapy.
Participants must have documented progressive disease as per RECIST v1.1 while on/after treatment with targeted therapy.

Criterios de exclusión

Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:
≤ 4 weeks for radiation therapy or ≤ 2 weeks for limited field radiation for palliation prior to the first dose of study treatment.
≤ 2 weeks for small molecule therapeutics.
≤ 4 weeks for any immunotherapy treatment including immune checkpoint inhibitors.
≤ 4 weeks for chemotherapy agents, locally directed anti-neoplastic agents, or other investigational agents.
≤ 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosourea and mitomycin c.
Participants participating in additional parallel investigational drug or medical device studies.
All primary central nervous system (CNS) tumors or symptomatic CNS metastases that are neurologically unstable History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.

Intervenciones

drug

LXH254

LXH254 will be supplied as tablet for oral use.

drug

LTT462

LTT462 will be supplied as hard gelatin capsule for oral use.

drug

Trametinib

Trametinib will be supplied as film-coated tablet for oral use

drug

Ribociclib

Ribociclib will be supplied in tablets and hard gelatin capsules.

Ubicaciones

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Patrocinadores

PrincipalNovartis Pharmaceuticals

Aviso: La información de este ensayo proviene de fuentes públicas y tiene carácter exclusivamente informativo. No constituye asesoramiento médico, regulatorio ni de ningún otro tipo. Las traducciones son automatizadas y no poseen validez oficial. Consultá siempre con un profesional de la salud. Ver Términos de Uso.

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