Pembrolizumab Glioblastoma Trial Identifies Vorinostat MTD in Combination

Trial results for the Phase 1 study (NCT03426891) investigating pembrolizumab and vorinostat combined with temozolomide for newly diagnosed glioblastoma were posted on ClinicalTrials.gov on 2025-10-06. The study identified maximum tolerated doses (MTDs) of vorinostat at 100 mg/day and 300 mg/day in the dose escalation phase. Median overall survival for one treatment level was 12.2 months.

Background

Pembrolizumab (Keytruda) is an immunotherapy drug approved by the U.S. Food and Drug Administration (FDA) for treating melanoma and lung cancer. Vorinostat is also FDA-approved for certain blood and lymph node cancers. In this study, both drugs were considered investigational for the treatment of glioblastoma, a type of aggressive brain tumor.

Trial design

The study (NCT03426891) was a Phase 1 trial titled "Pembrolizumab and Vorinostat Combined With Temozolomide for Newly Diagnosed Glioblastoma." It enrolled 21 participants with newly diagnosed glioblastoma. The trial investigated the safety and tolerability of the combination of vorinostat and pembrolizumab with temozolomide chemotherapy and radiotherapy. The primary objective was to determine the maximum tolerated dose (MTD) of the combined regimen.

Key results

Key results from the trial focused on determining the maximum tolerated dose and evaluating overall survival. For the outcome of "Maximum Tolerated Dose (MTD)" in the Dose Escalation Phase, vorinostat MTDs were identified at 100 mg/day and 300 mg/day. Regarding "Overall Survival (OS)," the median OS for the Level 1 group was 12.2 months. Median OS for other groups, Level -1 and Radiotherapy and Maintenance Phase, was reported as not available (NA).

What this means

The identification of maximum tolerated doses for vorinostat in combination with pembrolizumab and temozolomide is a crucial step for this investigational regimen in glioblastoma. As a Phase 1 study, the primary goal was to assess safety and determine appropriate dosing for potential future studies. The reported median overall survival for one treatment level provides preliminary insights into the regimen's potential, though further research would be needed to establish efficacy.

Source

The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03426891, titled "Pembrolizumab and Vorinostat Combined With Temozolomide for Newly Diagnosed Glioblastoma," were posted on 2025-10-06 on clinicaltrials.gov.