Lancet Oncol: Treatment of Relapsed/Refractory Malignant Pleural Mesothelioma with EZH2 Inhibitor Tzemetostat

There are few treatments for malignant pleural mesothelio.

Tzemetostat, an oral selective inhibitor of zeste homolog 2 (EZH2), has shown antitumor activity in several hematological cancers and solid tumo.

This study was designed to evaluate the antitumor activity and safety of Tzemetostat in measurable relapsed or refractory malignant pleural mesothelio.

This is an open-label, single-arm, Phase 2 trial in 16 hospitals in multiple countries, recruiting patients aged 18 years and older with relapsed or refractory malignant pleural mesothelial disease treated with a pemetrexed-containing regimen Patients with tumor, and require ECOG performance status 0-1 points, life expectancy longer than 3 mont.

In the first part of the study, the dosing regimen of Tzemetostat was 800 mg once on the first day and 800 mg twice a day on the second d.

In the second part of the study, 800 mg twice a d.

21 days as a course of treatment, about 17 courses of treatme.

The primary endpoint of the first part was the pharmacokinetics of Tzemetostat and its metabolites after day 15 of dosi.

The primary endpoint of the second part was disease control rate at week 1

overall survival

Between July 29, 2016, and June 2, 2017, a total of 74 patients (13 in part 1 and 61 in part 2) were recruited to receive Tzemetostat, of whom 73 (99%) were BAP1 Inactive tumo.

_{In the first part, repeated dosing at steady state, the mean maximum serum concentration ( Cmax} ) of Tzemetostat was 829 ng/mL on day 15 of the first cycle, and the mean time to Cmax ( _{Tmax )} was two hours (range 1-4), the mean area under the concentration-time curve (AUC _0-t ) was 3310 h·ng/mL, and the geometric mean half-life (t _1/2 ) of Tzemetostat was 1 hours

Treatment Response for Each Patient

In the second part, after a median follow-up of 39 weeks, the disease control rate in patients with BAP1 inactivation at week 12 was 54%

In conclusion, we need to further refine biomarkers other than BAP1 inactivation that can be indicative of Tzemetostat activity in malignant pleural mesothelioma, thereby assisting in the identification of patients who would clearly benefit from Tzemetostat treatme.

Original source:

Marjorie G Zauderer, et .