A new phase 1 clinical trial aims to evaluate the safety, side effects, and best doses of the combination of the anticancer drugs tazemetostat and belinostat for the treatment of recurrent or refractory diffuse large B-cell lymphoma (DLBCL) and other lymphomas.

The study is sponsored by the National Cancer Institute, which aims to explore the drugs and ways they “may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.”

During the trial, participants will receive oral tazemetostat twice daily on days 2 to 21 of their first 21-day cycle. On subsequent cycles, they will receive tazemetostat on days 1 to 21. Patients will also receive intravenous infusions of belinostat over 30 minutes on days 1 to 5 of each cycle. The cycles will continue until disease progression or unacceptable toxicity is observed.

Read more about DLBCL experimental therapies

The study’s primary outcome is to determine the maximum tolerated dose, calculated as the highest dose less than 33% of the dose cohort experienced dose-limiting toxicity in the first cycle. 

Secondary outcomes will include disease response, overall response rate, progression-free survival, overall survival, duration of response, the total number of cycles, number of dose delays, number of dose reductions, pharmacokinetics, and adverse events.

Additional outcome measures may include a description of immune modulation, histone acetylation, methylation, and modulation of these processes as well as an analysis of gene signature biomarkers.

An estimated 36 patients with recurrent or refractory DLBCL germinal center B-cell type (GCB-DLBCL), lymphoma, or transformed non-Hodgkin lymphoma (TNHL) will be recruited for the study. No study locations have been announced, but the trial is estimated to begin on December 9, 2022. Its completion date is estimated as March 1, 2024.

The initial dose escalation phase of the trial will recruit only patients with lymphoma but will expand the inclusion criteria to incorporate patients with GCB-DLBCL and TNHL during the dose expansion phase. In the dose expansion phase, patients will be equally divided into 2 arms: those with mutated EZH2 or wild-type EZH2 genes as identified by polymerase chain reaction.

Reference

Testing the safety of the anti-cancer drugs tazemetostat and belinostat in patients with lymphomas that have resisted treatment. ClinicalTrials.gov. November 25, 2022. Accessed November 29, 2022.