Update on phase 1 study of tazemetostat, an enhancer of zeste homolog 2 inhibitor, in pediatric patients with relapsed or refractory integrase interactor 1–negative tumors.

• DOI: 10.1200/jco.2022.40.16_suppl.10040
• Publication Date: 2022-06-06T17:31:24Z
• Authors: Susan N. Chi; Franck Bourdeaut; Michela Casanova; Lindsay Baker Kil...; Darren R. Hargrave; Geoffrey Brian Mc...; Navin R. Pinto; Jay Yang; Raminder Chadha; Bhaskar Kahali; Coya Tapia; Karsten Nysom
• Keywords: Tolerability; Clinical endpoint; Synovial Sarcoma; Interim analysis

10040 Background: A defining feature of malignant rhabdoid tumors (MRTs), epithelioid sarcoma (ES), and poorly differentiated chordomas (PDC) is loss integrase interactor 1 (INI1) expression, which induces dependence on enhancer zeste homolog 2 (EZH2). Tazemetostat (TAZ) a selective EZH2 inhibitor approved by the US Food Drug Administration for patients (pts) aged ≥16 y with metastatic or locally advanced ES ineligible complete resection. Pediatric dose escalation interim efficacy safety data expansion were previously reported. Updated efficacy, safety, subgroup analyses, translational results are reported here. Methods: NCT02601937 phase multicenter study evaluating TAZ monotherapy ≤2400 mg/m daily in pediatric pts relapsed refractory INI1 − (MRT, atypical teratoid tumor [ATRT], select features, other tumors, SS18-SSX synovial sarcoma). Primary endpoint was objective response rate (ORR). Secondary endpoints included safety/tolerability, duration (DOR), progression-free survival (PFS), overall survival. Selected exploratory flow using 250,000 cells from peripheral blood available up to 25 pts. Results: Phase enrolled 109 (escalation, n=46; expansion, n=63; Table) mean ages 5.4 7.4 expansion. ORRs 7% (3/46) 14% (9/63) Per category 24% (5/21) ATRT, 33% (2/6) PDC, 22% (2/9) ES, 0% non–CNS RTs (n=21) (n=6). ORR prior radiotherapy (11/80) vs 3% (1/29) ( P>0.05). In median PFS 8 wk (95% CI: 8–13), OS 21 13–38), DOR 35 24–121). Grade 3–4 treatment-related treatment-emergent adverse event rates 15% (7/46) (14/63) Differences between responders (R) nonresponders (NR) at C1D1 neutrophil counts significant P<0.05). All R (6/6) had <125,000 total neutrophils 42% (8/19) NR; 50% (3/6) >50,000 CD3 T (0/19) NR. Conclusions: showed promising antitumor activity PDC. Potential synergism requires further investigation. generally well tolerated. The biological/clinical significance differences cell NR needs Clinical trial information: NCT02601937. [Table: see text]