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

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Editor's note
Blocking autophagy may reverse drug resistance in a subset of colorectal cancers—a finding that flips the usual narrative where cellular recycling prevents disease. This is early clinical evidence for a mechanism-driven hypothesis rather than established practice, and the field remains divided on whether autophagy inhibition helps or harms in oncology. Medical oncologists treating BRAF-mutated colorectal cancer and researchers studying treatment resistance should watch this trial closely.

Source: ctgov · Northwestern University · RECRUITING · 2026-05-26

URL: https://clinicaltrials.gov/study/NCT05576896

AI rationale (4/5, tier: emerging): Phase II clinical trial testing autophagy inhibition (hydroxychloroquine) to overcome BRAF-inhibitor resistance in cancer; directly addresses autophagy's dual role in oncology.

This is a Phase II, open label, single-arm trial study of adding hydroxychloroquine to encorafenib and cetuximab in patients with metastatic BRAF V600E colon cancer with progression on at least 1 prior line of therapy. We hypothesize that autophagy is a major mechanism of resistance to BRAF inhibition in stage IV BRAF V600E colorectal cancer, and that the addition of hydroxychloroquine to standard encorafenib and cetuximab therapy will help overcome this resistance.

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Published 2026-05-28 · Last kit-update 2026-05-28