P1/2, N=86, Not yet recruiting, Ruijin Hospital

Despite progress in understanding ES biology, treatment options are limited, and prognosis remains poor. Further studies are needed, but the rarity of the disease limits opportunities for conducting dedicated clinical trials or broader molecular characterization.

The study developed EIP103 as a first-in-class peptide degrader that targets EZH2 through multivalent, high-affinity interactions and induces conformational destabilization, representing a mechanism distinct from that of the small molecule inhibitor EPZ-6438...Additionally, molecular dynamics (MD) simulations and biochemical assays revealed that the peptide EIP103 binds to the SET domain of EZH2, altering its structure and triggering proteasomal degradation via Praja Ring Finger Ubiquitin Ligase 2 (PJA2)-mediated ubiquitination. Harboring both enzymatic inhibition and post-translational regulation properties, EIP103 exerts durable efficacy and activates antitumor immunity, making it a promising therapeutic candidate for TNBC.

P2, N=25, Recruiting, Fudan University | Trial primary completion date: Feb 2026 --> Feb 2027

An 80-year-old woman with relapsed nodal T-follicular helper cell lymphoma, not otherwise specified, developed severe watery diarrhea during valemetostat therapy...To the best of our knowledge, this is the first reported case of enhancer of zeste homolog 1 and 2 (EZH1/2) inhibitor-induced colitis. EZH1/2 inhibition may lead to T cell-mediated intestinal injury through epigenetic dysregulation; therefore, patients receiving EZH1/2 inhibitors who develop persistent diarrhea should undergo early endoscopic and histological evaluations.

P1, N=4, Not yet recruiting, Daiichi Sankyo Inc.

P2, N=20, Terminated, Prisma Health-Upstate | N=40 --> 20 | Trial completion date: Jan 2028 --> Mar 2026 | Recruiting --> Terminated | Trial primary completion date: Jan 2027 --> Mar 2026; Ipsen has discontinued all active tazemetostat clinical trials and expanded access programs due to the emergence of a clinically unfavorable benefit risk profile for tazemetostat in combination with lenalidomide and rituximab.

P1, N=18, Active, not recruiting, National Cancer Institute (NCI) | N=60 --> 18 | Trial primary completion date: Apr 2027 --> Feb 2026

P2, N=62, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2026 --> Feb 2027

At the last follow-up, four patients were alive without disease, four were alive with disease, and three died due to progressive disease. Hence, valemetostat is a promising salvage therapy for relapsed adult T-cell leukemia/lymphoma after allo-HCT.

P1, N=453, Recruiting, Pfizer | Trial completion date: Mar 2029 --> Jul 2029

P1, N=60, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting