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Soo Park, MD
Soo Park, MD
Posted: Thursday, October 3, 2024
Hypomethylation combined with immune checkpoint inhibition may improve clinical outcomes for patients with metastatic melanoma resistant to PD-1 inhibitors, according to Anna M. Di Giacomo, MD, of University Hospital of Siena, Italy. In this patient population, the hypomethylating agent guadecitabine followed by the CTLA-4 inhibitor ipilimumab and the PD-1 inhibitor nivolumab appeared to be safe with . The results of this randomized, noncomparative, multicenter phase II study were presented at the European Society for Medical Oncology (ESMO) Congress 2024 (Abstract LBA47).
“We had shown that the hypomethylating agent guadecitabine, a prodrug of decitabine, followed by ipilimumab is safe, with promising clinical and immune-modulating activity in metastatic melanoma patients,” stated the investigators. “We report results from the run-in and stage I phase of the metastatic melanoma cohort.”
An initial safety run-in and pharmacokinetic study used guadecitabine (n = 2), which was then replaced by an oral fixed-dose combination of 20 mg decitabine and 10 mg of cedazuridine (also known as ASTX727; n = 4). For this portion of the study, patients with stage IV metastatic melanoma received guadecitabine (n = 2) or ASTX727 (n = 4) plus ipilimumab and nivolumab. In this patient population, responses included partial responses (n = 3), stable disease (n = 2), and progressive disease (n = 1). Adverse events of grade 3 or higher were reported in 50% of patients. There were no apparent differences in decitabine and guadecitabine pharmacokinetic analyses.
For stage 1 of the study, patients with stage III metastatic melanoma (n = 36) received ASTX727 plus ipilimumab and nivolumab or ipilimumab and nivolumab alone. The objective response rates were 39% for patients who received ASTX727 plus immune checkpoint inhibition and 17% for those who received immune checkpoint inhibition alone, with disease control rates of 56% and 33%, respectively. Adverse events of 3 or higher were reported in 72% of patients who received ASTX727 and immune checkpoint inhibition and in 50% of patients who received immune checkpoint inhibition alone.
Disclosure: For full disclosures of the study authors, visit cslide.ctimeetingtech.com.
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