Pembrolizumab Plus Vorinostat a Potential Combo for Lung Cancer

A phase I/Ib study published in Clinical Cancer Research found that treatment with the immune checkpoint inhibitor (ICI) pembrolizumab plus the histone deacetylase inhibitor vorinostat was well tolerated and demonstrated preliminary anti-tumor activity in patients with non-small cell lung cancer (NSCLC).

Patients received pembrolizumab 200 mg intravenously every three weeks plus vorinostat 200 mg or 400 mg orally per day.

A total of 33 patients were treated: 13 in phase I and 20 in phase Ib. In phase I, both those who had and had not previously received ICIs were enrolled to determine dose-limiting toxicities (DLTs); however, no DLTs were observed, and the recommended phase II dose was pembrolizumab 200 mg and vorinostat 400 mg.

Demonstrated safety and efficacy with pembrolizumab plus vorinostat

The most common adverse events associated with the combination therapy were fatigue (33%) and nausea/vomiting (27%).

A total of six ICI-naïve and 24 ICI-pretreated patients were evaluable for response, and the researchers observed a 67% disease control rate. Four patients (13%) had partial response (PR; two confirmed, one unconfirmed with subsequent prolonged stable disease [SD], and one unconfirmed with subsequent progressive disease [PD]), 16 (53%) had an SD, and 10 (33%) had a PD. In the ICI-pretreated cohort, three patients (one confirmed, two unconfirmed) had a PR and 10 had an SD.

Patients who had higher levels of T cells within the stromal environment prior to treatment had improved outcomes to this combination therapy, according to the authors.

This study is ongoing in a phase II setting assessing ICI-naïve patients with advanced/metastatic NSCLC.