Phase 2 trial data being presented at the virtual 2020 ASCO Annual Meeting demonstrate the antitumor activity of tazemetostat in patients with BAP1-deficient relapsed or refractory malignant mesothelioma.

According to lead investigator Marjorie Glass Zauderer, MD, MS, FACP, Memorial Sloan Kettering Cancer Center, New York, and colleagues, preclinical data shave shown that inactivation of BAP1, which is frequently inactivated in malignant mesothelioma, sensitizes mesothelial cells to inhibition of EZH2.

Thus, Dr Zauderer et al sought to assess the safety and efficacy of tazemetostat, a selective EZH2 inhibitor, in patients with relapsed or refractory malignant mesothelioma with BAP1-inactivation in the open-label, 2-part EZH-203 clinical trial.

A total of 74 patients were enrolled in the study, 70 (95%) of whom had confirmed BAP-1 deficiency. These patients had received a median of 2 previous lines of therapy.

In part 1 of the study, patients received 1 dose of tazemetostat 800 mg on day 1 of cycle 1 and tazemetostat 800 mg twice daily thereafter. In part 2, patients were given tazemetostat 800 mg twice daily on day 1 of cycle 1.

The main end points of the study were the pharmacokinetic profile of tazemetostat (part 1) and the 12-week disease control rate (part 2). The secondary end points included safety, overall response rate (ORR), progression-free survival, overall survival, and response duration.

Ultimately, the 12-week disease control rate was 47% (n = 35), and the ORR was 3% (complete response, 0%; partial response, 3%). Notably, 1 of the 2 patients with a partial response had a duration of response of 21 weeks and the other’s is ongoing (15.3 weeks as of data cutoff).

Stable and progressive disease was observed in 47 (64%) and 21 (28%) patients, respectively, and 91% of patients discontinued therapy because of disease progression (n = 65), death (n = 5), or treatment discontinuation (n = 1).

Although treatment-emergent AEs grade ≥3 occurred in ≤5% of patients, with the most common being anemia (5%) and dyspnea (4%), there were no reports of therapy discontinuation due to treatment-related AEs or treatment-related deaths.

“Based on disease control rate and stable disease, tazemetostat showed antitumor activity in patients with BAP1-deficient relapsed or refractory malignant mesothelioma. Tazemetostat monotherapy was generally well-tolerated,” Dr Zauderer and colleagues concluded.

“The current data support further clinical evaluation of tazemetostat in these patients. Furthermore, this trial presents an optimal paradigm for drug development in molecularly-enriched cohorts in mesothelioma,” they added.—Hina M. Porcelli

Zauderer MG, Szlosarek PW, Le Moulec S, et al. Safety and efficacy of tazemetostat, an enhancer of zeste-homolog 2 inhibitor, in patients with relapsed or refractory malignant mesothelioma. Presented at: the 2020 ASCO Annual Meeting; May 29-31, 2020. Abstract 9058.