9530Background: Immune checkpoint inhibitors (ICIs) have improved prognosis for pts with advanced melanoma, but there is an unmet need for pts who progress after ICI. In this group, we reported that ENT, a class I selective histone deacetylase (HDAC) inhibitor, in combination with PEMBRO showed promising activity, through alteration of the immunosuppressive tumor microenvironment. Here we report the first 34 pts with further information on both prior therapies and pre/on treatment tumor samples. Methods: ENCORE-601 is a multicohort study evaluating ENT + PEMBRO. Pts enrolled in Cohort 3 had unresectable or metastatic melanoma, were previously treated with a PD-(L)1-blocking antibody, and experienced progression on or after therapy. The enrollment target was 34 pts and revised to 52 to increase statistical power and decrease Type I error. Pts were treated with ENT 5 mg PO weekly and PEMBRO 200 mg IV Q3W. Primary endpoint was ORR as assessed by irRECIST. Tumor biopsies and blood samples for immune correlate...