Tazemetostat Active in Non-Hodgkin Lymphomas, Solid Tumors
The recommended phase 2 dose is 800 mg twice daily.
Tazemetostat may be safe and effective in some patients with non-Hodgkin lymphomas or solid tumors, according to research published in The Lancet Oncology.1
Tazemetostat, a selective inhibitor of EZH2, showed preclinical activity against EZH2-mutant non-Hodgkin lymphomas, INI1-negative rhabdoid tumors, and SMARCA4-negative rhabdoid tumors of the ovary. For this phase 1 study (ClinicalTrials.gov Identifier: NCT01897571), researchers enrolled patients with relapsed/refractory non-Hodgkin lymphoma or locally advanced/metastatic tumors to assess the drug's safety and efficacy.
Sixty-four patients were enrolled between 2013 and 2016; 21 had B-cell non-Hodgkin lymphoma (13 had diffuse large B-cell lymphoma, 7 had follicular lymphoma, and 1 had marginal zone lymphoma), and 43 had a solid tumor. In the lymphoma and solid tumor groups, the median ages were 62 and 55 years, respectively, and all patients had a median 3 prior lines of therapy.
The most frequently noted treatment-related adverse events (AEs) were asthenia (33%), anemia (14%), muscle spasms (14%), nausea (13%), vomiting (9%), and anorexia (6%), though most were grade 1 or 2.
Grade 3 to 4 treatment-related AEs, although uncommon, were noted: thrombocytopenia (4%), neutropenia (4%), hepatocellular injury (2%), and hypertension (2%). The cases of grade 4 thrombocytopenia were dose-limiting; the recommended phase 2 dose was set at 800 mg twice daily.
Seven patients died on study, though no deaths were treatment-related.
Complete or partial responses were noted in 38% of patients with non-Hodgkin lymphoma and in 5% of patients with a solid tumor.
The authors concluded that “tazemetostat inhibits EZH2, as evidenced by reduction of trimethylation of H3K27, and can induce durable tumour responses in patients with B-cell non-Hodgkin lymphoma and INI1-negative or SMARCA4-negative tumours with a favourable safety profile.” Phase 2 studies are ongoing.
- Italiano A, Soria JC, Toulmonde M, et al. Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study. Lancet Oncol. 2018 Apr 9. doi: 10.1016/S1470-2045(18)30145-1