Investigational Drug Combo May Enhance Immune Checkpoint Inhibitor Response in NSCLC

An early clinical trial demonstrated positive results for a new drug combination in patients with non-small cell lung cancer (NSCLC), according to a study published in Clinical Cancer Research.

Improvements in lung cancer treatment, such as the emergence of immune checkpoint inhibitors (ICIs), have provided new treatment options for patients; however, even with these advancements, many patients’ disease will still progress.

In preclinical studies, researchers have found that drugs called histone deacetylase (HDAC) inhibitors have the ability to stimulate the immune system and enhance the response to ICIs.

To assess these findings, researchers from the Moffitt Cancer Center evaluated the use of HDAC inhibitors in this patient population through a phase 1/1b study of pembrolizumab plus vorinostat in 33 patients with advanced or metastatic NSCLC. Despite progression on prior ICI treatment, pembrolizumab plus vorinostat appeared to be well tolerated and demonstrated preliminary anti-tumor activity, according to the findings.

For the study, patients received intravenous pembrolizumab (200 mg, every 3 weeks) plus oral vorinostat (200 or 400 mg per day).

Using correlative analysis, the researchers determined that patients with higher levels of T cells within the stromal environment before treatment had improved outcomes to therapy. The findings indicate that vorinostat may sensitize tumors to ICIs by causing T cells to migrate from the stroma to the tumor bed, the researchers noted.

Of the 30 patients who were evaluable for efficacy, 4 had a partial response to treatment and 16 had developed stable disease, for a disease control rate of 67%, according to the study. The most common treatment-related adverse effects were fatigue, nausea, and vomiting.

“We believe our results lay the groundwork for future trials to assess impact of epigenetic agents on ICI response, and the discovery of biomarkers to assess the dynamic nature of the immune response early in patient’s treatment course,” Amer Beg, PhD, senior member of the Department of Immunology at Moffitt, said in a press release.

References

Gray JE, Saltos AN, Tawee T, et al. Phase 1/1b study of pembrolizumab plus vorinostat in advanced/metastatic non-small cell lung cancer. Clinical Cancer Research. 2019. Doi: 10.1158/1078-0432.CCR-19-1305

New Drug Combination Shows Promising Activity in Non-Small Cell Lung Cancer Patients [news release]. Moffitt Cancer Center. https://moffitt.org/newsroom/press-release-archive/2019/new-drug-combination-shows-promising-activity-in-non-small-cell-lung-cancer-patients/. Accessed August 28, 2019.