Hydroxychloroquine in Combination With Encorafenib and Cetuximab or Panitumumab in the Treatment of Metastatic BRAF-mutated Colorectal Cancer Refractory

Primary Objective -Determine the Objective Response Rate (ORR) of encorafenib, cetuximab or panitumumab, and hydroxychloroquine in patients with stage IV BRAF V600E mutated colorectal cancer. Secondary Objectives -Determine progression-free survival (PFS) of patients treated with encorafenib, cetuximab or panitumumab, and hydroxychloroquine. Note: progression is defined as either radiological progression (with CT scan) OR clinical progression, which will be defined as 'clinical deterioration associated with rising CEA biomarker' (laboratory date of collection of sample to be noted). * Determine overall survival (OS) by RECIST v1.1 criteria of patients treated with encorafenib, cetuximab or panitumumab, and hydroxychloroquine. * Determine 'Duration of Response' (DoR) of patients treated with encorafenib, cetuximab or panitumumab, and hydroxychloroquine. * Determine 'Duration of Stable Disease'(DoSD) of patients treated with encorafenib, cetuximab or panitumumab, and hydroxychloroquine. * Estimate rates of drug-related toxicities when patients are treated with encorafenib, cetuximab or panitumumab, and hydroxychloroquine. OUTLINE: Prior to starting therapy, patients will have a pretreatment cross-sectional scan. Patients will then begin with encorafenib 300 mg daily starting with Cycle 1 day 1; then patients will receive IV cetuximab weekly, with 400 mg/m2 on C1D1 as a loading dose and 250 mg/m2 on all other days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months (+/- 1 month) for the next 18 months.