An updated analysis from the SYMPHONY-1 trial shows that combination therapy with tazemetostat plus lenalidomide and rituximab demonstrates consistent clinical activity with a favorable safety profile for patients with relapsed/refractory follicular lymphoma (FL). The findings from this analysis were presented at the 2022 ASCO Annual Meeting by Connie Batlevi, MD, Memorial Sloan Kettering Cancer Center, New York, NY.

“Tazemetostat, an enhancer of zeste homolog 2 (EZH2) inhibitor, showed antitumor activity as monotherapy in patients with relapsed or refractory FL who received ≥2 prior lines of therapy. In clinical studies in patients with [relapsed or refractory] FL, lenalidomide and rituximab demonstrated an objective response rate (ORR) of 73%–78% and median progression-free survival (PFS) of 36–39 months,” explained Dr Batlevi and colleagues.

In this phase 1b/3 study Dr Batlevi et al aimed to determine the recommended phase 3 dose, efficacy, and safety of tazemetostat plus lenalidomide and rituximab in patients with relapsed/refractory FL who received ≥1 prior therapy. A total of 3 dose levels were explored: 400 mg, 600 mg, and 800 mg orally twice daily in 28-day cycles with standard dosing of lenalidomide and rituximab.

This interim analysis reports pharmacokinetics, safety, and preliminary efficacy of the combination. The efficacy analysis was performed on the response-evaluable population. Primary end points included investigator assessed best overall response, PFS, and duration of response (DOR).

A total of 43 patients were enrolled and receiving tazemetostat plus lenalidomide and rituximab as of the data cutoff date of January 22, 2022. Of whom, 4 received a dose of 400 mg, 18 received a dose of 600 mg, and 21 received a dose of 800 mg. The median duration of treatment exposure was 32 weeks.

Mean C_max and AUC_0–t of tazemetostat at 800 mg combined with lenalidomide and rituximab at steady state were similar to those found for tazemetostat monotherapy. The analysis showed the pharmacokinetics of tazemetostat was not altered by concomitant administration of daily oral lenalidomide and the pharmacokinetics of lenalidomide was not altered by concomitant administration of tazemetostat.

Researchers reported no dose-limiting toxicities or new safety signals. Serious treatment-emergent adverse events (AEs) were reported for 14 (32.6%) of patients. Grade 3 to 4 treatment-emergent adverse events were reported for 24 (55.8%) patients. The most common grade 3 to 4 AE was neutrophil count decrease, which was observed in 13 (30.2%) patients.

There were 38 patients evaluable for tumor assessment. Of whom, 19 (50%) experienced a complete response, 17 (44.7%) experienced a partial response, and 2 (5.3%) had stable disease. The ORR was 94.7%. After a median follow-up of 5.8 months, median PFS and DOR were not reached.

[Tazemetostat plus lenalidomide and rituximab] combination demonstrates consistent and unaltered [pharmacokinetics] for tazemetostat and lenalidomide as well as a favorable safety profile and efficacy trend,” concluded Dr Batlevi and colleagues.

“The 2-arm randomized phase 3 portion will further explore the efficacy and safety of tazemetostat recommended phase 3 dose 800 mg [plus lenalidomide and rituximab] in ≈500 patients with [relapsed or refractory] FL,” they added.

Source:

Batlevi CL, Park SI, Phillips TJ, et al. Updated interim analysis of the randomized phase 1b/3 study of tazemetostat in combination with lenalidomide and rituximab in patients with relapsed/refractory follicular lymphoma. Presented at: American Society of Clinical Oncology; June 3-7, 2022. Chicago, IL, and virtual. Abstract 7572.