Tazverik (tazemetostat) / Eisai, Hutchmed, Ipsen, Royalty - LARVOL DELTA

Tazemetostat in Relapsed/Refractory follicular lymphoma and DLBCL: A systematic review of clinical trials (ASH 2025) - "Tazemetostat in combination with rituximab and lenalidomide regimen showed higher response even in high-risk subgroups, including WT, rituximab-refractory, and patients with disease progression. Ongoing phase 3 trials are evaluating tazemetostat-based regimens in both relapsed and untreated high-risk FL."

Clinical • Review • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Thrombocytopenia • EZH2

EZH2 inhibition synergizes with aiolos/ikaros degradation via coordinated chromatin remodeling and FoxO activation in multiple myeloma (ASH 2025) - P1/2 | "Background : Mezigdomide (Mezi, CC-92480) is a novel CRBN E3 ligase modulator (CELMoD) agent, thatinduces rapid and deep degradation of Ikaros and Aiolos, two transcription factors essential for multiplemyeloma (MM)...A recent clinical study (NCT05372354)demonstrated promising efficacy using a combination of Mezi, dexamethasone, and Tazemetostat (TAZ),an EZH2 inhibitor, in heavily pretreated MM patients... Our preliminary findings reveal a novel mechanism where EZH2 inhibition enhancesCELMoD efficacy by coordinating chromatin remodeling and transcriptional reprogramming in MM cellsleading to synergistic anti-proliferative activity. We propose that TAZ treatment increases chromatinaccessibility by reducing H3K27me3 repressive marks, thereby facilitating FoxO-driven tumor suppressorprograms concurrent with Aiolos/Ikaros degradation by Mezi. This dual-targeted approach represents arational and promising strategy to overcome resistance mechanisms in MM."

Hematological Malignancies • Multiple Myeloma • Targeted Protein Degradation • BMF • CRBN • IKZF1

Dissecting the whole trajectory of aid-induced genomic instability from mutational activity to chromosomal translocation formation (ASH 2025) - "EZH2 inhibitors, such as tazemetostat and valemetostat, areepigenetic regulators approved by the FDA for the treatment of follicular lymphoma and adult T-cell leukemia/lymphoma, respectively. Overall, to our knowledge this work represents the most comprehensive mapping of AID-inducedmutational and genotoxic activity, shedding light on the whole trajectory of AID activity from thevery early initiation steps of cytidine deamination to the formation of DSB intermediates up tothe final outcome of chromosomal translocations. The described approach can be exploited tofunctionally dissect the impact of novel drugs on AID-mediated genomic instability in B celllymphoma."

Adult T-Cell Leukemia-Lymphoma • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Gene Therapies • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Solid Tumor • PIK3CD

A phase 1b trial of the EZH2 inhibitor tazemetostat combined with CAR T cell therapy in B cell lymphomas (ASH 2025) - "4 patients had TP53 mutation or deletion(31%), and of the 7 DLBCL patients, 4 had high-grade myc translocation (57%) and 3 were transformedfrom indolent lymphomas (43%).Following tazemetostat pre-treatment and bridging, 5 patients received axi-cel (38%), 5 liso-cel (38%), 2tisa-cel (15%), and 1 brexu-cel (8%). Addition of the EZH2 inhibitor tazemetostat to the CAR T pre-collection, bridging, and post-infusion periods is feasible, and without early evidence of adverse impact on safety. Initial efficacy data isencouraging but requires additional patients and follow up. Preliminary correlative findings suggest apositive impact of tazemetostat oral administration on the endogenous immune system, tumormicroenvironment, and T cell product in patients."

CAR T-Cell Therapy • IO biomarker • P1 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Indolent Lymphoma • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia • CD4 • CD8 • MYC • TP53

Representation of older adults in registrational trials associated with therapeutic approvals in follicular lymphoma (ASH 2025) - "Of the drugs approved, 2 were bispecific antibodies (BsAb,epcoritamab, mosunetuzumab), 3 were chimeric antigen receptor-T (CAR-T) products (lisocabtagene,axicabtagene, tisagenleucel), 3 were PI3K inhibitors (umbralisib, copanlisib, duvelisib), 2 were monoclonalantibodies (obinutuzumab with chemotherapy, obinutuzumab with bendamustine), and 1 each ofselective EZH2 inhibitor (tazemetostat), immunomodulator (lenalidomide with rituximab), and BTKinhibitor (zanubrutinib). Most registrational trials for FL do report a subgroup of OA, although inclusion of OAremains suboptimal at 37%. Representation and reporting of pts≥ 75 yrs is significantly low at only 8%,despite this group representing 20% pts at diagnosis. Reporting of trials should include and distinguishpts ≥65 yrs and ≥75 yrs for subgroup analyses."

Clinical • Follicular Lymphoma • Geriatric Disorders • Hematological Malignancies • Lymphoma

Multiple reciprocal interactions within B-cell receptor and AKT signaling pathways regulate response to EZH2 inhibition in germinal center-derived diffuse large B-cell lymphoma (ASH 2025) - "Tazemetostat, a highlyspecific EZH2 inhibitor (EZH2i), is FDA-approved for relapsed or refractory FL with EZH2 mutation but hasshown only limited efficacy in DLBCL...Our findings providefurther rationale for combining EZH2 inhibition with inhibitors of other targets, such as BCR signalingmediators, in treating lymphoma.First two authors contributed equally. Supported by GACR (20-01969Y), MHCR (DRO - VFN00064165),National Institute for Cancer Research (EXCELES - LX22NPO5102), and MEYSCR (Cooperatio, SVV 260637)."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • CD19 • CD79A • EZH2 • mTOR • PIK3CD • PTEN • SYK

Epigenetic reprogramming via EZH1/2 inhibition enhances T cell-mediated immunotherapies against multiple myeloma (ASH 2025) - "Introduction:Although BCMA-targeted CAR-T therapies and CD3×BCMA bispecifics (e.g., teclistamab) have shownclinical promise, most r/r MM patients eventually relapse due to tumor-intrinsic resistance and T-celldysfunction...We, therefore, hypothesized that inhibition of EZH1 and EZH2 could enhance T cell–basedimmunotherapy for MM by both directly impairing tumor growth and survival, and by boosting T cell–mediated cytotoxicity.Methods and We first demonstrated a strong tumor-intrinsic anti-clonogenic effect of the EZH2 inhibitor (tazemetostat)and the dual EZH1/2 inhibitor (valemetostat) on the MM cell line RPMI-8226... These findings support a dual mechanism of action EZH1/2 inhibitors directly suppress MMclonogenicity and immune evasion, while concurrently enhancing the function and cytotoxicity of T cell–based immunotherapies. By preserving T-cell activity and reprogramming tumor cells, EZH1/2 inhibitionrepresents a promising strategy to improve the durability and..."

IO biomarker • B Cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • CD31 • CD70 • CXCL10 • CXCL14 • CXCL9 • EZH2 • IFNG • IL2 • LAMA1 • LAMA2 • PECAM1 • SDC2

Results of part 1 of a two-part study evaluating the combination of tazemetostat and CPX-351 (part 1) and palbociclib with CPX-351 (part 2) for the treatment of relapsed or refractory Acute Myeloid Leukemia (ASH 2025) - "Inpreclinical studies, AML cell lines treated with the combination of an EZH2 inhibitor (EZH2i) anddoxorubicin exhibited increased DNA damage and apoptosis compared to those treated with doxorubicinalone...Similar levelsof H3K27me3 and DNA-damage were observed at TAZ dose levels 1 and 2, suggesting that no additionalbiologic activity was observed at the higher dose level. Dose level 1 has been selected as therecommended Part 3 dose."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • TAFAZZIN

Dual HDAC and EZH2 inhibition modulates RFX5 activity to increase the immunogenicity of germinal center-derived B-cell lymphoma (ASH 2025) - P1 | "Belinostat (BEL), an HDAC inhibitor, and tazemetostat (TAZ), an EZH2inhibitor, counteract the epigenetic derangements caused by CREBBP and EZH2 mutations, and togetherincrease immune activity and antigen presentation targets to create a "hot" tumor environment. RFX5 expression was knocked down (KD) in SU-DHL-4 cells usingsiRNAs. RFX5 WT and KD cells were treated with vehicle, BEL, TAZ, or BEL+TAZ for six days and co-cultured with T cells for 24 h. Decreased cell viability was observed in the RFX5 WT cells but not the KDsfollowing treatment (n=3), revealing the critical role of RFX5 expression in BEL+TAZ-mediated cell kill.Lastly, RFX5 knockout (KO) murine A20 lymphoma cells were generated using CRISPR-Cas9 gene editing.An experiment is currently underway evaluating tumor growth and overall survival in vehicle-, BEL-, TAZ-,and BEL+TAZ-treated BALB/c mice xenografted with either RFX5 WT or KO murine A20 cells.In conclusion, dual HDAC and EZH2 inhibition..."

B Cell Lymphoma • Gene Therapies • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • B2M • CD4 • CD8 • CREBBP • HLA-DQA1 • HLA-DRA • TAFAZZIN

Embryonic ectoderm development (EED) inhibitor APG-5918 overcomes immunomodulatory drug (IMiD) resistance as monotherapy and synergizes with IMiDs/cereblon E3 ligase modulators (CELMoDs) in preclinical models of multiple myeloma (MM) (ASH 2025) - "Introduction IMiDs (eg, lenalidomide, pomalidomide) are approved for the treatment of patients with MM and otherhematologic malignancies...We assessed antitumor activity and mechanisms of APG-5918 (± IMiDs orCELMoDs) in preclinical MM models.MethodsA genetically diverse panel of MM cell lines, including IMiD-resistant (KMS11, MOLP-8, U266, RPMI-8226)and -sensitive (AMO-1, OPM-2, MM.1S) lines, were used to assess in vitro antiproliferative activity of APG-5918 (± pomalidomide or CELMoD CC-92480)...APG-5918 showed potent antiproliferativeactivity across most IMiD-sensitive and -resistant cell lines, with low nanomolar to submicromolar IC50values, indicating efficacy regardless of IMiD sensitivity and superior antiproliferative effects vs. EZH2inhibitor tazemetostat...Combined withpomalidomide, it restores IMiD signaling via IRF4 suppression and reinforces cell cycle arrest bydownregulating CDK4/pRb, resulting in synergistic antitumor activity. These findings..."

Immunomodulating • Monotherapy • Preclinical • Hematological Malignancies • Multiple Myeloma • Targeted Protein Degradation • ANXA5 • CASP3 • CDK4 • CRBN • IKZF1 • IKZF3 • SUZ12

Epigenetic silencing via SP140 and H3K27me3 restricts immunogenic viral antigen expression in EBV+ lymphomas (ASH 2025) - "Consequently, allogeneic EBV-CTLs are effective cellular therapy in latency II/III tumors but are largely ineffective against latency Itumors such as EBV+ Burkitt lymphoma (BL) and subsets of diffuse large B-cell lymphoma (DLBCL).We previously showed that DNMT1 inhibition with decitabine (DCB) can partially induce latency II/III geneexpression in latency I BL, sensitizing tumors to EBV-CTLs...The elevation in H3K27me3 at Cp and LMP1p was confirmed in an additional BL cell line(Rael) and in DLBCL (Val).Based on this, we evaluated the EZH2 inhibitor, tazemetostat (TAZ), which reduces H3K27me3...Dual inhibition of DNMT1 and EZH2 enhances expression of immunogenicviral antigens, improving tumor susceptibility to EBV-CTLs. This strategy offers a promising approach fortreating otherwise immune-refractory EBV+ lymphomas."

B Cell Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Epstein-Barr Virus Infections • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • EZH2 • IFNG • SP140

fss25-103: Beyond Chemotherapy: Patient Voices and Expert Insights on Using Precision Therapies to Enhance Personalized Care of Follicular Lymphoma (ASH 2025) - "Learn how to optimize the use of bispecific antibodies, CAR T-cell therapy, and novel targeted agents such as tazemetostat, tafasitamab, and BTK inhibitors. Stay ahead of the curve with highlights of emerging clinical trial data and future directions in FL management. This symposium will challenge your clinical perspective, deepen your understanding of the shifting FL landscape, and empower you to deliver more personalized, evidence-informed care."

Clinical • Follicular Lymphoma • Hematological Malignancies • Lymphoma

HUTCHMED Announces…Inclusion in the First Commercial Insurance Drug List in China (GlobeNewswire) - "TAZVERIK (tazemetostat) is included in the Commercial Insurance Drug List for the treatment of adult patients with relapsed or refractory follicular lymphoma with EZH2 mutation who have received at least two prior systemic therapies. In July 2025, the NHSA issued the 2025 Adjustment Work Plan for the NRDL and the Commercial Health Insurance Innovative Drug List, announcing the establishment of the new Commercial Insurance Drug List. This list, together with the NRDL, forms a key component of China’s multi-level medical insurance system."

Reimbursement • Follicular Lymphoma

Pharmacological inhibition of or reduced EZH2 levels sensitized diffuse intrinsic pontine gliomas (DIPG) to ONC201, leading to synthetic lethality (SNO 2025) - "RNA-seq showed that ONC201 and EHZ2 inhibitor tazemetostat-treated cells exhibited similar transcriptional profiles, sharing top-regulated genes...In contrast, there was no overlap in the transcription or cytokine profiles obtained after ONC201 and Panobinostat (an HDAC inhibitor) treatment... ONC201 and EHZ2 inhibition converge on nodes within the same linear pathway and exhibit synthetic lethal interactions. These findings bear therapeutic implications and provide the foundation for drug combinations with ONC201."

Synthetic lethality • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioma • Solid Tumor • EZH2

Efficacy of Protac-Based EZH2 Degrader MS1943 in Lymphoid Malignancies: A Comprehensive Study on the Combined Effects of MS1943 and Ibrutinib (ASH 2023) - "The results demonstrated that MS1943 exhibited significantly greater inhibitory effects than Tazemetostat in all lymphoma cell lines tested, particularly in B-cell lymphomas. MS1943 treatment resulted in increased expression of UPR pathway effectors, suggesting a correlation between the observed anti-proliferative effects and the differential expression of these factors. The combination of MS1943 and Ibrutinib demonstrated significant inhibitory effects across all B-cell lymphoma cell lines, with the most prominent cytotoxicity observed after 72 hours of culture."

Clinical • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • Targeted Protein Degradation • BBC3 • XBP1

TREATMENT OF ADVANCED EPITHELIOID SARCOMA WITH COMBINATION TAZEMETOSTAT AND PEMBROLIZUMAB (CTOS 2025) - "Here we present data from two patients at a single institution treated with tazemetostat in combination with immune checkpoint inhibitor therapy. We conducted a retrospective review of two patients with advanced ES treated with combination tazemetostat and pembrolizumab (PD-1 inhibitor) 200 mg every three weeks at our institution. Patient A, a 38-year-old man, presented with ES of the right hemipelvis, treated with neoadjuvant adriamycin/cisplatin, surgery, and adjuvant radiation (RT). Four years later found to have metastatic disease, treated with gemcitabine/paclitaxel, pazopanib, and targeted RT...Two years later found to have metastatic disease, treated with vincristine/cyclophosphamide/ifosfamide/etoposide, gemcitabine/docetaxel, pazopanib, and targeted RT... In both cases, pembrolizumab was added to tazemetostat at progression, yielding sustained and durable response for treatment of ES. This demonstrates the potential for combination epigenetic regulation and..."

Metastases • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

PRECLINICAL VALIDATION OF M3554, A NOVEL ANTI-GD2 ANTIBODY-DRUG CONJUGATE, AND EPIGENETIC SENSITIZATION STRATEGIES IN SOFT TISSUE SARCOMAS (CTOS 2025) - P1 | "In this study, we evaluated the preclinical efficacy of M3554 in GD2-expressing STS models and explored the potential of EZH2 inhibition to upregulate GD2 expression as prior findings showed that EZH2 can silence ganglioside biosynthesis genes. GD2 surface expression was assessed via flow cytometry in STS cell lines with or without the EZH2 inhibitor tazemetostat, followed by analysis of ganglioside biosynthetic enzyme expression. M3554 is a promising anti-GD2 ADC with strong preclinical activity in GD2-expressing STS cell lines. Epigenetic modulation using EZH2 inhibition effectively upregulates GD2 expression, potentially enhancing therapeutic response and expanding the range of treatable tumors. These findings support the clinical development of M3554 in STS populations and provide a rationale for combining GD2-targeted therapies with epigenetic modulators."

Preclinical • Brain Cancer • Glioblastoma • Liposarcoma • Neuroblastoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • EZH2

IMPACT OF PRIOR SYSTEMIC THERAPY ON TAZEMETOSTAT EFFICACY IN ADVANCED EPITHELIOID SARCOMA: POST HOC ANALYSIS OF STUDY EZH-202 (CTOS 2025) - No abstract available

Clinical • Metastases • Retrospective data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

A PHASE 2 MULTICENTER OPEN-LABEL BASKET STUDY OF TAZEMETOSTAT IN ADULT PATIENTS WITH INI1-NEGATIVE EPITHELIOID SARCOMA – FINAL ANALYSIS (CTOS 2025) - P2 | "A notable proportion of pts with advanced/progressive INI-neg ES had durable responses to Taz, which was generally well tolerated (low TRAEs, dose reduction and discontinuation rates), and positive exposure–efficacy relationships were identified. These findings support further studies of Taz in pts with epithelioid sarcoma.Clinical outcomes in C5 and C6"

Clinical • P2 data • Pan tumor • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

EZHIP: A NOVEL EPIGENETIC DRIVER OF OSTEOSARCOMA PATHOGENESIS (CTOS 2025) - "EZHIP and H3K27me3 loss are novel mechanisms in osteosarcoma (OS) pathogenesis. While H3K27me3 loss is a poor prognostic marker, it also presents a therapeutic opportunity especially in chemoresistant OS, through the use of Tazemetostat and other EZH2 inhibitors. Further investigation combining Tazemetostat with current standards of care for patients with refractory tumors is warranted."

Oncology • Osteosarcoma • Sarcoma • Solid Tumor • EZH2

Title: A phase 1b trial of the EZH2 inhibitor tazemetostat combined with CAR T cell therapy in B cell lymphomas (Businesswire) - "BostonGene to Showcase...Abstracts at the 67th American Society of Hematology Annual Meeting & Exposition....Based on the premise that inhibition of EZH2 prevents T cell exhaustion and modulates T cell activity, the phase I study administered tazemetostat with CAR-T in patients with B-cell lymphoma. The combination resulted in an impressive 100% response rate with no signal of additional toxicity. BostonGene’s novel immunophenotyping is being performed to demonstrate the immune modulatory effects of combination therapy, providing mechanistic rationale for further combination approaches."

P1 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Mantle Cell Lymphoma

Enhancing Triple-Negative Breast Cancer Radiotherapy via EZH2-Targeted Nanoplatform and Radionuclide Therapy. (PubMed, Mol Pharm) - "A cancer cell membrane (CCm)-camouflaged nanoplatform (CCm-HSA-Taz) was engineered to encapsulate the EZH2 inhibitor Tazemetostat (Taz), enabling tumor-targeted delivery...Nuclear medicine imaging revealed reduced tumor glucose metabolism and improved immune cell cytotoxicity. Utilizing components approved by the FDA suggests the potential for this strategy to be translated into clinical settings."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • EZH2

Tazverik: Regulatory submission for 2L follicular lymphoma (based on SYMPHONY-1 trial) in 2027 (HUTCHMED) - Corporate Presentation

Filing • Follicular Lymphoma • Hematological Malignancies • Oncology

EFFICACY OUTCOMES AMONG PATIENTS WITH ADVANCED EPITHELIOID SARCOMAS OF PROXIMAL-TYPE AND DISTAL-TYPE TREATED WITH TAZ: POST HOC ANALYSIS OF STUDY EZH-202 (CTOS 2025) - P2 | "Objective: To report efficacy outcomes of patients (pts) with proximal-type epithelioid sarcoma (pES) and distal-type ES (dES) treated with tazemetostat (TAZ) in the Phase 2 study EZH-202 (NCT02601950), a multicenter, open-label, single-arm basket trial with results reported so far only for a single cohort (cohort 5). This post-hoc unplanned analysis of ES pts in EZH-202 (Pooled Cohorts 5 and 6) stratified pts by ES subtypes... Baseline pt characteristics prior to EZH-202 enrollment showed a more severe clinical presentation in pES compared to dES, as expected. TAZ demonstrated anticancer efficacy both in pts with pES and dES. Despite small differences in the magnitude of anticancer efficacy, no conclusions can be drawn given small patient numbers and overlapping 95% CIs."

Clinical • Metastases • Retrospective data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Characterizing resistance in prostate cancer at a single cell level with hormonal treatment and epigenetic inhibitors. (PubMed, J Pharm Pharmacol) - "This work characterizes at a single-cell level the Enzalutamide resistant clone and the impact of epigenetic inhibitors on resistance development. This characterization may enable the identification of resistant and non-resistant cells by their gene expression profile."

Journal • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • AR • CDC37 • CDKN1A • DDIT3 • HSP90AB1 • POLH