Resumen

El subestudio 02B forma parte de un estudio de investigación más amplio en el que los investigadores buscan nuevas formas de tratar el melanoma avanzado que no ha recibido tratamiento previo. El estudio más amplio es el estudio umbrella. Los investigadores desean saber si agregar otros tratamientos al pembrolizumab puede tratar el melanoma avanzado. Los objetivos de este estudio son conocer: * La seguridad y la tolerabilidad del pembrolizumab administrado junto con otros tratamientos. * Cuántas personas presentan un melanoma que responde (disminuye o desaparece) al tratamiento.

Descripción detallada

Con la Enmienda 6, todos los brazos están cerrados a la inscripción. Los participantes en los brazos 2 (pembrolizumab), 3 (coformulación pembrolizumab/quavonlimab) y 4 (coformulación pembrolizumab/quavonlimab + lenvatinib) que completen el tratamiento del estudio o que cumplan de otro modo los criterios de fin de tratamiento (FDT) serán discontinuados del estudio tras completar la visita de FDT y las visitas de seguimiento de seguridad requeridas. Los participantes del brazo 6 (coformulación favezelimab/pembrolizumab + ácido all-trans retinoico [ATRA]) discontinuarán el ATRA, y los participantes de los brazos 5 y 6 podrán continuar con la coformulación favezelimab/pembrolizumab o con pembrolizumab.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 120 YearsSexo: ALL

Criterios de inclusión

Has histologically or cytologically confirmed melanoma
Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy
Has been untreated for advanced disease.
Has provided a tumor biopsy
If capable of producing sperm, male participants agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention (7 days):
Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR
Uses contraception unless confirmed to be azoospermic
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
Is not a WOCBP OR
Is a WOCBP and Uses a contraceptive method that is highly effective, with low user dependency, or be abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
MK-4280A: 120 days
MK-1308A: 120 days
MK-7684: 50 days
MK-3475: 120 days
Lenvatinib: 30 days
ATRA: 30 days
Has adequate organ function
Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia and Grade 2 neuropathy)

Criterios de exclusión

Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days before the first dose of study intervention
Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
Has ocular or mucosal melanoma
Has an active autoimmune disease that has required systemic treatment in the past 2 years
Has an active infection requiring systemic therapy
Has known history of human immunodeficiency virus (HIV)
Has history of Hepatitis B or known Hepatitis C virus infection
Has a history of (noninfectious) pneumonitis
Has a history of active tuberculosis (TB)
Has received prior systemic anticancer therapy within 4 weeks prior to randomization
Has received prior radiotherapy within 2 weeks of first dose of study intervention
Has had major surgery \<3 weeks prior to first dose of study intervention
Has received a live vaccine within 30 days before the first dose of study intervention
Has participated in a study of an investigational agent within 4 weeks prior to the first dose of study intervention
Has had an allogeneic tissue/solid organ transplant
Has a known psychiatric or substance abuse disorder that would interfere with requirements of the study
Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula
Has radiographic evidence of encasement of invasion of a major blood vessel, or of intratumoral cavitation
Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study intervention
Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
Has urine protein ≥1 g/24-hour.
Has presence of gastrointestinal condition including malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib

Intervenciones

biological

Pembrolizumab

Administered via IV infusion at a specified dose on specified days

biological

Vibostolimab

Administered via IV infusion at a specified dose on specified days

biological

Pembrolizumab/Quavonlimab

Administered via IV infusion at a specified dose on specified days

drug

Lenvatinib

Administered via oral capsule at a specified dose on specified days

biological

Favezelimab/Pembrolizumab

Administered via IV infusion at a specified dose on specified days

drug

ATRA

Administered via oral capsule at a specified dose on specified days

Diseño de plataforma umbrella de brazo rotativo de fase 1/2, abierto, con agentes en investigación con o sin pembrolizumab o pembrolizumab solo en participantes con melanoma (KEYMAKER-U02): Subestudio 02B

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Pembrolizumab

Vibostolimab

Pembrolizumab/Quavonlimab

Lenvatinib

Favezelimab/Pembrolizumab

ATRA

Ubicaciones

Clinica Adventista Belgrano-Oncology ( Site 2242)

Instituto Alexander Fleming-Alexander Fleming ( Site 2243)

Sanatorio Finochietto ( Site 2245)

Patrocinadores