Skip to main content

Epizyme Exploring Tazverik Combinations in Basket Trials

NEW YORK – Epizyme on Tuesday said it will initiate two basket studies in the second half of 2021 to evaluate the activity of tazemetostat (Tazverik) across various hematologic cancers and solid tumors.

Company executives discussed the studies as part of a presentation on the company's strategic plans over the next five years. The presentation focused in large part on Epizyme's program for its lead product tazemetostat, which is already approved for relapsed or refractory follicular lymphoma patients with EZH2-mutated tumors who have had two prior systemic therapies and for refractory patients who don't have such mutations but are out of options. The drug is also approved for metastatic or locally advanced epithelioid sarcoma patients who are ineligible for complete resection.

According to Epizyme CEO Robert Bazemore, the company is focused on moving tazemetostat into earlier settings in patients with follicular lymphoma and epithelioid sarcoma, and in combination with other drugs in a variety of solid and hematologic cancers.

Toward that end, the company has planned an open-label, Phase I/II basket trial in which it will investigate tazemetostat in combination with other agents in six cohorts of patients with follicular lymphoma, diffuse large B-cell lymphoma (DLBCL), mantel cell lymphoma, and multiple myeloma. In the Phase I portion, researchers will enroll six patients to establish the safety of these combinations and move them into a Phase II expansion portion involving 20 patients in each cohort to track efficacy signals.

Several cohorts in this basket trial will explore tazemetostat combinations based on promising preclinical activity in certain biomarker-defined indications. For example, Epizyme will pair tazemetostat with an unnamed bispecific antibody based on preclinical evidence of synergistic activity between its drug and rituximab (Genentech/Biogen's Rituxan) in an EZH2-mutant DLBCL in vitro model.

In another cohort, the company will explore tazemetostat and a CD19 antibody in DLBCL patients. "When looking at various subsets of DLBCL, we see increases in CD19 expression when treating with tazemetostat, particularly those that contain EZH2 mutations," Shefali Agarwal, Epizyme's executive VP and chief medical and development officer, said during the strategic update presentation.

The second Phase I/II basket trial will explore the activity of tazemetostat paired with a PARP inhibitor or a checkpoint inhibitor in four solid tumor cohorts involving patients with small cell lung, prostate, and ovarian cancer. Specifically, in a cohort of small cell lung cancer patients who are chemotherapy ineligible in the first-line setting, Agarwal said researchers will explore the safety of the tazemetostat-checkpoint inhibitor regimen, as well as clinical and biomarker-based efficacy signals.

These basket trials are signal-finding trials, Agarwal said, aimed at identifying indications where tazemetostat combination regimens have promising activity that Epizyme should explore in larger cohorts. These multi-cohort studies should shorten development timelines, she added.