Pembrolizumab–vorinostat combo shows antitumour activity in advanced/metastatic NSCLC

In the treatment of patients with advanced/metastatic nonsmall cell lung cancer (NSCLC), the combination of pembrolizumab plus vorinostat has a tolerable safety profile and demonstrates preliminary antitumour activity despite progression on prior immune checkpoint inhibitor (ICI) therapy, according to the results of a phase I/Ib trial.

Thirty-three patients received intravenous pembrolizumab (200 mg every 3 weeks) plus oral vorinostat (200 or 400 mg/day). Phase I (open-label dose escalation; n=13) involved both ICI-naïve and ICI-pretreated patients, whereas phase Ib (dose expansion; n=20) included only those who had received prior ICI therapy.

There were no dose-limiting toxicities (DLT) recorded. The recommended phase I dose was 200 mg for pembrolizumab and 400 mg for vorinostat. Fatigue (33 percent) and nausea/vomiting (27 percent) were the most common any-grade adverse events.

Response was evaluable in six ICI-naïve and 24 ICI-pretreated patients overall. In the treatment-naïve cohort, there was one confirmed partial response (PR), four cases of stable disease (SD) and one case of progressive disease (PD). Disease control rate (DCR) was 83 percent. Median progression free survival (PFS) and overall survival (OS) were 7.5 months and 16.0 months, respectively.

In the ICI-pretreated cohort, three patients (one confirmed, two unconfirmed) had PR, 11 (46 percent) had SD and 10 (42 percent) had PD, for a DCR of 58 percent. Pretreatment CD8+ T-cell presence in tumour stromal regions was associated with treatment benefit.

The respective median PFS and OS were 4.6 months and 7.3 months in the ICI-relapsed NSCLC subgroup (n=11), and 2.8 months and 6.8 months in the ICI-refractory NSCLC group (n=13).

Researchers noted that the ongoing randomized phase II study will examine whether pembrolizumab plus vorinostat improves RR and PFS compared with pembrolizumab alone in ICI-naïve advanced/metastatic NSCLC patients.