hydroxychloroquine + dabrafenib + trametinib

Hydroxychloroquine sulfate is an oral small molecule autophagy inhibitor being repurposed by the ECOG-ACRIN Cancer Research Group for the treatment of advanced melanoma. In the Phase II BAMM2 (EA6191) trial, hydroxychloroquine is evaluated in combination with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib. This therapeutic regimen specifically targets patients with stage IIIC or IV BRAF V600E/K mutant melanoma who have elevated lactate dehydrogenase (LDH) levels and have progressed after prior immunotherapy. The rationale for this combination is that BRAF and MEK inhibition can trigger autophagy as a survival mechanism in melanoma cells, leading to treatment resistance. By inhibiting autophagy, hydroxychloroquine aims to sensitize tumor cells to MAPK pathway inhibition and delay disease progression. The BAMM2 study is a randomized, double-blind, placebo-controlled trial initiated following promising results from the earlier single-arm BAMM study.

Brand names

PlaquenilTafinlarMekinist

Other names

hydroxychloroquine-ECOG-ACRIN Cancer Research Group-melanomahydroxychloroquine sulfateBAMM2 regimenBAMM-2 regimenBAMM 2 regimen