What question did this study set out to answer?

To evaluate the efficacy and safety of Entinostat plus Pembrolizumab in patients with metastatic melanoma previously treated with anti-PD-1 therapy.

May 29, 2026

Final results and correlative analysis of entinostat (E) plus pembrolizumab (P) in patients (Pts) with metastatic melanoma (MM) previously treated with anti–PD-(L)1 therapy (Tx).

Key Points

To evaluate the efficacy and safety of Entinostat plus Pembrolizumab in patients with metastatic melanoma previously treated with anti-PD-1 therapy.
53 patients with unresectable stage III/IV metastatic melanoma were treated with Entinostat and Pembrolizumab.
Primary endpoint was objective response rate based on irRECIST criteria; secondary endpoints included safety, progression-free, and overall survival.
Correlative analyses of tumor biopsies and blood were performed to assess immune response.
19% of patients achieved a partial or complete response, with a median follow-up of 11.5 months.
49% of patients experienced grade 3/4 toxicity, with 19% discontinuing treatment due to adverse events.
Increased immune infiltration was observed in tumors, correlating with clinical benefits, especially in those with inflamed tumor profiles.

Abstract

9522 Background: PD(L)1 inhibitors have transformed MM tx, yet several pts experience resistance. Preclinical data suggest that epigenetic modifications may overcome this. Here, we present the results of an expansion MM cohort treated with E+P following prior anti-PD(L)1 tx. Methods: Pts with unresectable stage III/IV melanoma, progression to anti-PD(L)1 and BRAF-targeted tx (if BRAF -mutant) were eligible. Pts were treated with E, 5 mg PO qwk, and P, 200 mg IV q3wks. The primary endpoint was to determine the objective response rate (ORR) per the irRECIST criteria. Secondary endpoints included assessment of the safety of E+P tx, progression-free (PFS), and overall survival (OS). Correlative analyses were performed on baseline and on-tx tissues. Results: 53 pts were treated (median mdn age, 61 years; 60% male; 55% with ECOG performance status of 0; 64% with visceral metastases; 23% with BRAFV600 mutation), including 43% with primary resistance to anti-PD(L)1 inhibitors, respectively. The mdn number of prior systemic tx was 3 (range 1-8), and 70% of pts had previous tx with CTLA4 inhibitors. 49% pts developed ≥ grade 3/4 toxicity, and 19% pts discontinued at least one drug due to adverse events. 10 pts had a partial (n=9) or complete (n=1) response, for an ORR of 19%. The mdn follow-up was 11.5 months (mon), and the mdn response duration was 23.7 mon (range 2.6-45.6+ mon); 9 pts had stable disease > 6 mon. The mdn PFS and OS were 4.0 and 11.5 mon, respectively. Blood analysis showed that the tx significantly decreased Ki67-PD1+ T cells and T regs and significantly increased Ki67-HLA-DR+ and ICOS+ T cells. Analysis of baseline (n=30) and on-tx (n=10) tumor biopsies using NanoString and/or bulk RNAseq showed increased immune infiltration with tx and increased expression of key genes in antigen presentation ( ß2M ), chemoattraction ( CXCL11 the most significant benefit, however, was observed in pts with pre-existing inflamed tumors. Clinical trial information: NCT02437136 .

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Cite This Study

Moschos et al. (Thu,) studied this question.

synapsesocial.com/papers/6a192e18fab5b468c44171da https://doi.org/https://doi.org/10.1200/jco.2026.44.16_suppl.9522

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