Encorafenib + Binimetinib + Pembrolizumab in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma

Exclusion Criteria

• •Currently participating in or having participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• •Diagnosis of immunodeficiency or receiving systemic steroid therapy in dosing exceeding 10 mg daily of prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to study Day 1.
• •Prior therapy (except if given as adjuvant or neoadjuvant therapy for melanoma) with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways (except for interferon given as adjuvant or neoadjuvant therapy for melanoma).
• •Prior therapy (except if given as adjuvant or neoadjuvant therapy for melanoma) with a BRAF inhibitor (including but not limited to vemurafenib, dabrafenib, encorafenib) and / or MEK inhibitor (including but not limited to trametinib, AZD6244, binimetinib, cobimetinib).
• •Any previous anti-cancer treatment, extensive radiotherapy or investigational agent for locally advanced unresectable or metastatic melanoma.
• •Known additional malignancy that is progressing or required active treatment within 3 years prior to the study.
• •Known active CNS metastases and/or carcinomatous meningitis.
• •Presence of uveal melanoma.
• •History of leptomeningeal metastases.
• •History or current evidence of CSR or RVO or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, history of hyperviscosity or hypercoagulability syndromes).
• •History of retinal degenerative disease.
• •History of allogeneic bone marrow transplantation or organ transplantation.
• •History of Gilbert's syndrome.
• •Uncontrolled arterial hypertension despite medical treatment.
• •Patients who have neuromuscular disorders associated with elevated creatine kinase (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
• •Impairment of gastrointestinal function or gastrointestinal disease (e.g. ulcerative disease, uncontrolled nausea, vomiting, malabsorption syndrome, small bowel resection).
• •Evidence of interstitial lung disease or active, non-infectious pneumonitis or history of (non-infectious) pneumonitis that required steroids.
• •Active infection requiring systemic therapy.
• •Pregnancy or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit until up to 120 days after the last dose of trial treatment.
• •Positive test for HIV.
• •Positive test for Hep B or Hep C.
• •Receiving a live vaccine within 30 days prior to the first dose of trial treatment.
• •Known hypersensitivity reaction to any of the components of study treatment.
• •Medical, psychiatric, cognitive or other conditions, including known alcohol or drug abuse that would not permit the subject to complete the study or sign informed consent.
• •Patients taking non-topical medication known to be a strong inhibitor of CYP3A4.
• •History of life-threatening toxicity related to prior immune therapy (e.g. anti-CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) or kinase inhibition (e.g. BRAF and/or MEK inhibitor) except those that are unlikely to re-occur with standard countermeasures (e.g. hormone replacement after adrenal crisis).