Eisai Co., Ltd:...announced today that it has obtained manufacturing and marketing approval for the EZH2 inhibitor “Tazverik® Tablets 200 mg” (tazemetostat hydrobromide) in Japan with the indication of relapsed or refractory EZH2 gene mutation-positive follicular lymphoma...

...the FDA approved the EZH2 inhibitor for use in patients with relapsed/refractory follicular lymphoma who also have tumors that harbor EZH2 mutations, as detected by an FDA-approved test, and who have received a minimum of 2 prior systemic therapies or have no other satisfactory treatment options available to them.

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...To determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of tazemetostat as a single agent administered orally twice daily (BID), continuously in 28-day cycles in subjects with advanced solid tumors or with relapsed and/or refractory B cell lymphomas`Maximum tolerated dose (MTD) (Phase 1 only)`To determine the objective response rate (ORR; complete response + partial response [CR + PR]) of tazemetostat in subjects with enhancer of zeste homolog 2 (EZH2) gene mutation positive or negative (wild-type) with histologically confirmed diffuse large B cell lymphoma (DLBCL) or follicular lymphoma (FL), with relapsed or refractory disease and the ORR of tazemetostat in combination with prednisolone in subjects with EZH2 wild-type DLBCL`Objective response rate (ORR; complete response + partial response [CR + PR]) (Phase 2)...

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...Have provided sufficient tumor tissue to test for EZH2 mutation status and cell of origin at study-specific laboratories....

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...objective response rate in cohort 1 was 76.5%, including six patients (35.3%) with complete response and seven patients (41.2%) with partial response (PR)....Tazemetostat 800 mg BID showed encouraging efficacy in patients with relapsed or refractory EZH2 mutation-positive FL with a manageable safety profile in the overall population. Thus, tazemetostat may be a potential treatment for relapsed or refractory EZH2 mutation-positive FL.

...ORR was 35% (95% CI [22%, 48%]) in the WT and 69% (95% CI [55%, 83%]) in MT EZH2 groups; after matching, the ORR was 50% (95% CI [31%, 69%]) and 71% (95% CI [54%, 88%]), respectively. Median PFS was 11.1 months (95% CI [5.4, 16.7]) in the WT and 13.8 months (95% CI [11.1, 22.1]) in the MT EZH2 groups prior to matching....efficacy remained higher in the MT EZH2 group

Patients received 800 mg of tazemetostat orally twice per day in continuous 28-day cycles….99 patients (45 in the EZH2 mut cohort and 54 in the EZH2 WT cohort) were enrolled in the study….The objective response rate was 69% (95% CI 53–82; 31 of 45 patients) in the EZH2 mut cohort and 35% (23–49; 19 of 54 patients) in the EZH2 WT cohort.

The ORR (CR + PR) was 40% in pts with DLBCL with EZH2 mutations (N  = 10), 18% in pts with DLBCL with wt EZH2 (N  = 85), 63% in FL pts with EZH2 mutations (N  = 8), and 28% in FL pts with wt EZH2 (N  = 46)….This phase 2 interim assessment shows preliminary clinical activity of tazemetostat with a favourable safety profile in pts with R/R DLBCL and FL, with preferential benefit in pts whose tumours bear activating EZH2 mutations.

Tazmetostat 800 mg is administered orally….phase 2 safety and efficacy data were summarized from 76 FL patients...In patients with an activating EZH2 mutation (n=22), the ORR (complete response [CR] + partial response [PR]) was 82%, with best overall response of CR 5% (n=1), PR 77% (n=17), stable disease (SD) 18% (n=4), and no patients with progressive disease (PD).

...EZH2 inhibitor tazemetostat is effective against relapsed or refractory follicular lymphoma. Three of 28 patients with EZH2 mutations had complete responses, and 17 had partial responses.

Tazemetostat was orally administered at a single dose of 800 mg on the first day and 800 mg twice daily...An EZH2 mutation was detected in one patient with FL responding to treatment.

Given the presence of an activating EZH2 mutation he was treated with an EZH2 inhibitor (tazemetostat) and is in ongoing complete response at 34 months on therapy.