Tazemetostat Shows Promise in Refractory B-Cell NHL and Advanced Solid Tumors

Tazemetostat therapy yields favorable safety and antitumor activity in patients with refractory B-cell non-Hodgkin lymphoma (NHL) and advanced solid tumors (Lancet Oncol. 2018;19[5]:649-659).

“Activating [EZH2] mutations or aberrations of the switch/sucrose non-fermentable (SWI/SNF) complex…can lead to aberrant histone methylation, oncogenic transformation, and a proliferative dependency on EZH2 activity,” explained Antoine Italiano, MD, Institut Bergonié, Bordeaux, France, and colleagues, who sought to evaluate the safety, clinical activity, pharmacokinetics, and pharmacodynamics of tazemetostat in patients with relapsed or refractory B-cell NHL or advanced solid tumors.

A total of 64 patients with Eastern Cooperative Oncology Group performance status 0 or 1, including 21 with B-cell NHL and 43 with advanced solid tumors, were included in the multi-center, open-label clinical trial between June 13, 2013, and September 21, 2016.

Patients were given tazemetostat 100 mg to 1600 mg twice daily in 28-day cycles, and the primary end point was to establish the maximum tolerated dose of tazemetostat, based on dose-limiting toxicities, laboratory values, and other safety or pharmacokinetic measures in cycle 1.

The most frequently reported treatment-related adverse events were grade 1 or 2 asthenia (33%), anemia (14%), anorexia (6%), muscle spasms (14%), nausea (20%), and vomiting (9%). A single dose-limiting toxicity of grade 4 thrombocytopenia was identified at the highest dose of 1600 mg twice daily. There were no treatment-related mortalities, although 7 nontreatment-related deaths occurred.

Ultimately, the recommended phase 2 dose of tazemetostat was determined to be 800 mg twice daily. Durable objective responses, including complete responses, were reported in 8 (38%) patients with B-cell NHL and 2 (5%) patients with solid tumors.

“Tazemetostat showed a favourable safety profile and antitumour activity in patients with refractory B-cell [NHL] and advanced solid tumours, including epithelioid sarcoma,” Dr Italiano and colleagues concluded.

“Further clinical investigation of tazemetostat monotherapy is ongoing in phase 2 studies in adults and a phase 1 study for children, which are currently enrolling patients who have B-cell [NHL] and INI1-negative or SMARCA4-negative tumours,” they added.—Hina Khaliq