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

TAZEMETOSTAT IN COMBINATION WITH R-CHOP IN PATIENTS WITH HIGH-RISK, FRONTLINE FOLLICULAR LYMPHOMA (Epi-RCHOP) IN NEED OF THERAPY: A PHASE II STUDY FROM THE LYSA (ICML 2025) - "In this very high-risk selected subset of front-line FL, combining TAZ + RCHOP was efficient but without a clear signal of superiority compared to standard immunochemotherapy. Moreover, the safety profile including 3 cases of AML warrants caution and myeloid NGS investigation of the entire cohort is ongoing."

Clinical • Combination therapy • P2 data • Acute Myelogenous Leukemia • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Pembrolizumab and Tazemetostat to Overcome Immune Tolerance Following ASCT or CAR T-cell Therapy in Patients With Aggressive B-Cell Non-Hodgkin's Lymphoma (clinicaltrials.gov) - P2 | N=11 | Active, not recruiting | Sponsor: Northwestern University | N=32 ➔ 11

Enrollment change • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • IRF4

Mezigdomide (MEZI), tazemetostat (TAZ), and dexamethasone (DEX) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): preliminary results from the CA057-003 trial (IMW 2024) - P1/2 | "The third agent in each combination intervenes on a key oncogenic pathway upregulated in RRMM: 1) EZH2 inhibitor TAZ for PRC2 complex dysregulation; 2) BET inhibitor BMS-986158 for CKS1B (on chromosome 1q) amplification; 3) or MEK inhibitor trametinib for RAS-RAF-MEK-ERK activation. MEZI+TAZ+DEX showed promising preliminary efficacy and safety in pts with RRMM, with no new safety concerns."

Clinical • Anemia • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Plasmacytoma • Pulmonary Disease • Septic Shock • CKS1B • IKZF1

Tazemetostat in combination with topotecan and pembrolizumab in patients with recurrent small cell lung cancer. (ASCO 2024) - P1 | "The study involves collection of mandatory biopsies at pre-treatment and post-treatment (cycle 1) to gain insights into mechanism of action and resistance of the combination using single cell and spatial transcriptomic approaches. For more questions regarding enrollment and eligibility please contact or ."

Clinical • Combination therapy • IO biomarker • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • SLFN11 • TOP1

Therapeutic Effects of Inhibitors to Putative DTP-associated Pathways in EGFR-mutant Lung Cancer PDX Models (IASLC-WCLC 2026) - "Our goal is to assess the efficacy of inhibitors targeting these DTP markers in osimertinib (osi)-induced DTPs of EGFR -mutant PDX models. Methods : DTPs were induced in PDX models with EGFR ex19del (PHLC137) by oral gavage with osi (25 mg/kg QD) and osi combination treatment with bemcentinib (AXL inhibitor, 50 mg/kg BID), BI-847325 (AURK inhibitor, 10 mg/kg QD), valemetostat (EZH1/2 inhibitor, 100 mg/kg QD), tazemetostat (EZH2 inhibitor, 500mg/kg QD), or selinexor (XPO1 inhibitor, 10 mg/kg QD)...Conclusions : In patient-derived models, AXL pathway and epigenetic regulators may represent additional vulnerabilities in osi-induced DTPs. However, despite delay in regrowth, all single agent combination treatments with osi did not achieve complete eradication of the DTP cells, suggesting that multiple combinatorial strategies may be required to overcome DTPs."

IO biomarker • Lung Cancer • Oncology • Solid Tumor • EGFR • EZH2

Single-nuclei ATACSeq identifies JunB and KLF as key nodes in the acquisition of an immunotolerant state by airway neutrophils in people with CF (NACFC 2026) - "We tested the effect of two epigenome-modifying compounds, namely, EPZ6438 (an EZH2 inhibitor) and SIS17 (an HDAC11 inhibitor), which we know restore normal bactericidal activity in CF airway neutrophils, in order to interrogate pathogen clearance–associated epigenetic and transcriptional states... Together, deep epigenetic and transcriptional profiling reported here (Figure 1) show that JunB and KLF are central to GRIM fate acquisition in CF airway neutrophils, an immunomodulatory program that is active in pwCF, even on CFTR modulators, but is not restricted to CF. We also provide proof-of-concept data suggesting that specific drugs altering the epigenome of airway-recruited neutrophils can normalize their fate and bactericidal activity, as a novel approach to treat residual airway disease in pwCF, irrespective of CFTR variants and/or modulator use."

IO biomarker • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Respiratory Diseases • CD63 • CSF1R • EGFR • HDAC11 • JUNB • PD-1 • PD-L1

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

Mezigdomide (MEZI) in Novel-Novel Combinations for Relapsed or Refractory Multiple Myeloma (RRMM): Preliminary Results from the CA057-003 Trial (ASH 2024) - P1/2 | "The CA057-003 phase 1/2 trial (NCT05372354) is evaluating all-oral, novel-novel targeted triplet combination regimens using a MEZI plus dexamethasone (DEX) (MEZId) backbone in patients (pts) with RRMM. The third agent in each combination intervenes on a key oncogenic pathway identified by The Myeloma Genome Project to be upregulated in RRMM : the EZH2 inhibitor tazemetostat (TAZ) for PRC2 complex dysregulation, the BET inhibitor BMS-986158 for CKS1b (located on Chr 1q) amplification, and the MEK inhibitor trametinib (TRAM) for RAS-RAF-MEK-ERK activation...These results provide a rationale for further exploration of these novel all-oral combinations. Accrual continues and updated results will be presented at the meeting."

IO biomarker • Multiple Myeloma • Neutropenia • Plasmacytoma • CKS1B • IKZF1

Phase II Trial of Ubamatamab in MUC16-Expressing SMARCB1-Deficient Renal Medullary Carcinoma and Epithelioid Sarcoma (KCRS 2024) - "As proof of concept, a 20-year-old patient with metastatic SMARCB1-negative ES expressing high levels of serum CA125 achieved a durable (12+ months) partial response to ubamatamab after progressing on multiple prior therapies, including EZH2 inhibition with tazemetostat as well as antiPD1/CTLA4 immune checkpoint inhibition with nivolumab plus ipilimumab...Patients with disease progression on ubamatamab monotherapy during Stage I can proceed to stage II, which will evaluate the combination of ubamatamab with cemiplimab combination...Mucin 16 (cancer antigen 125) Expression in Epithelioid Sarcoma leads to Single-Patient Study with Bispecific T-Cell Engager Ubamatamab (Mucin16xCD3): A Bench-ToBedside Experience. Connective Tissue Oncology Society, Nov 16–19, 2022, Vancouver, Canada."

IO biomarker • P2 data • Cardiovascular • Kidney Medullary Carcinoma • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Respiratory Diseases • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • MUC16 • SMARCB1

EZH2 inhibitor tazemetostat in patients with relapsed or refractory, BAP1-inactivated malignant pleural mesothelioma: a multicentre, open-label, phase 2 study. (PubMed, Lancet Oncol) - P2 | "Further refinement of biomarkers for tazemetostat activity in malignant pleural mesothelioma beyond BAP1 inactivation could help identify a subset of tumours that are most likely to derive prolonged benefit or shrinkage from this therapy."

Journal • P2 data • Diabetes • Hematological Disorders • Hematological Malignancies • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor • BAP1

Tazemetostat in Combination with R-CHOP in Patients with High-Risk, Frontline Follicular Lymphoma (Epi-RCHOP): A Phase II Study from the Lysa (ASH 2023) - P1/2 | "Background: Tazemetostat (TAZ), an enhancer of zeste homolog 2 (EZH2) inhibitor, is approved by the US Food and Drug Administration for the treatment of patients with relapsed/refractory (R/R) follicular lymphoma (FL) whose disease has mutant (MT) EZH2 and who have received ≥2 prior therapies or with R/R FL who have no satisfactory alternative treatment options. Although the primary endpoint was not met due to missing BM assessments, TAZ + RCHOP combination demonstrated a promising complete metabolic response rate of 79% in this high-risk frontline FL population, with a manageable safety profile, after vincristine dose was reduced."

Clinical • Combination therapy • P2 data • Anemia • Follicular Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Thrombocytopenia • EZH2

Efficacy and safety results of tazemetostat in Japanese patients with advanced epithelioid sarcoma: The phase 2 TAZETTA trial (NCCH2107). (ASCO 2026) - P, P2 | "Eligible patients had locally advanced or metastatic epithelioid sarcoma with loss of INI1, had received at least one prior chemotherapy including doxorubicin, had an ECOG performance status of 0–2, and at least one measurable lesion according to RECIST v1.1. Tazemetostat demonstrated clinically meaningful activity and a manageable safety profile in Japanese patients with advanced epithelioid sarcoma, consistent with the previous reports, supporting its role as a therapeutic option in this population."

Clinical • Metastases • P2 data • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

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

Clinical activity of tazemetostat, an EZH2 inhibitor, among patients with advanced endometrioid endometrial cancer and ovarian clear cell carcinoma with and without ARID1A mutations (NRG-GY014) (SGO 2024) - P2 | "Among patients with recurrent, pre-treated EEC and OCCC, tazemetostat failed to show sufficient single-agent activity as defined by RECIST v1.1. Within the heavily pre-treated ARID1Amut OCCC cohort, a provocative 6-month PFS rate of 24.2% was noted (NRG Oncology NRG-GY014, clinicaltrials.gov number: NCT03348631)."

Clinical • Late-breaking abstract • Metastases • Colorectal Cancer • Endometrial Adenocarcinoma • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • ARID1A

Comparative Effectiveness of Tazemetostat in EZH2-Mutant Versus Wild-Type Relapsed/Refractory Follicular Lymphoma: A Systematic Review and Meta-Analysis (SOHO 2026) - "Tazemetostat demonstrates superior efficacy in EZH2-mutant R/R FL, supporting EZH2 mutation status as a prognostic biomarker. Nevertheless, noticeable clinical activity in a proportion of EZH2 wild-type patients suggests a wider therapeutic role for EZH2 inhibition. Future biomarker-driven studies are necessary to identify wild-type patients most likely to benefit from tazemetostat."

HEOR • Retrospective data • Review • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A pilot study of tazemetostat and pembrolizumab in advanced urothelial carcinoma (ETCTN 10183). (ASCO-GU 2023) - P1/2 | " ETCTN 10183 (NCT03854474) is a pilot study evaluating the efficacy of tazemetostat 800 mg BID + pembrolizumab 200 mg every 3 weeks for cisplatin-refractory (Cohort A) or cisplatin/chemo-ineligible advanced UC (Cohort B) pts, with N=12 pts in each cohort. The RP2D dose for tazemetostat is 800 mg + 200 mg Pembrolizumab q 3 weeks. The combination was feasible, well tolerated, and resulted in durable responses in poor-risk chemo-refractory UC patients. Clinical trial information: 03854474."

Clinical • IO biomarker • Metastases • Tumor mutational burden • Oncology • Solid Tumor • Urothelial Cancer • KDM6A • KMT2C • KMT2D • PD-L1 • TMB

Results of the Phase II of Epirchop Study, Evaluating the Efficacy of Tazemetostat in Combination with R-CHOP in Elderly Newly Diagnosed Diffuse Large B Cell Lymphoma (DLBCL): A Lysa Study (ASH 2023) - P1/2 | "Prophylaxis with G-CSF, valaciclovir and trimethoprim sulfamethoxazole were strongly recommended...In oct 2020, after the inclusion of 22 pts, recommendation to cap vincristine at 1mg was done, due to an excess of constipation... R-CHOP plus TAZ is doable. Efficacy results in this trial conducted during the COVID pandemic in a particularly challenging population, suggest that the combination warrant further investigation including correlative studies with molecular subclassification that will be presented."

Clinical • Combination therapy • P2 data • Acute Myelogenous Leukemia • Anemia • B Cell Lymphoma • Cardiovascular • Congestive Heart Failure • Constipation • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Septic Shock • Thrombocytopenia

Tazemetostat, an EZH2 inhibitor, in solid tumors harboring SWI/SNF alterations: a phase II basket study. (PubMed, Nat Commun) - P2 | "Grade ≥3 treatment-related adverse events occurred in 10% of patients. Tazemetostat demonstrated preliminary antitumor activity in a subset of poor-prognosis cancers, underscoring the need for combination strategies when EZH2 signaling is not the sole disease driver."

Journal • P2 data • Pan tumor • Chordoma • Kidney Medullary Carcinoma • Oncology • Renal Cell Carcinoma • Rhabdoid Tumor • Sarcoma • Solid Tumor • Synovial Sarcoma

Polycomb Repressive Complex 2 drives flow-sensitive endothelial states underlying vascular inflammation and disease. (PubMed, Proc Natl Acad Sci U S A) - "In murine models of acute and chronic vascular inflammation, interventional treatment with tazemetostat, a Federal Drug Administration (FDA)-approved inhibitor of the PRC2 methyltransferase EZH2, reduced endothelial inflammatory genes, slowed disease progression, and drastically improved markers of plaque stability. This study elucidates a fundamental epigenetic mechanism in vascular inflammation and suggests a potential treatment for advanced and chronic cardiovascular inflammatory diseases."

Journal • Atherosclerosis • Cardiovascular • Inflammation • Myocardial Infarction • KLF4

Epithelioid Sarcoma: A Review and Update. (PubMed, Cancers (Basel)) - "The withdrawal of tazemetostat has created a significant gap in available treatment options. In this review, we provide an overview of the current knowledge on the clinical and radiological features, histopathology, immunohistochemistry, pathogenesis, and management of EPS."

Journal • Review • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • SMARCB1

Study of Tazemetostat in Newly Diagnosed Diffuse Large B Cell and Follicular Lymphoma Patients Treated by Chemiotherapy (clinicaltrials.gov) - P1/2 | N=214 | Active, not recruiting | Sponsor: The Lymphoma Academic Research Organisation | Trial completion date: Apr 2026 ➔ Sep 2029

Trial completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Mezigdomide (MEZI) in Novel Targeted Combinations for Relapsed/refractory Multiple Myeloma (RRMM): Updated Results from the Phase 1/2 CA057-003 Trial (IMS 2025) - P1/2 | "CA057-003 (NCT05372354) is evaluating all-oral, novel triplet regimens with a MEZI+dexamethasone (DEX) (MEZId) backbone plus EZH2 inhibitor tazemetostat (TAZ), BET inhibitor BMS-986158, or MEK inhibitor trametinib (TRAM), in RRMM. MEZId plus TAZ, BMS-986158, or TRAM showed promising efficacy and safety in RRMM, supporting further exploration of these novel all-oral combinations."

P1/2 data • Multiple Myeloma • Neutropenia • Plasmacytoma • IKZF1 • NCOA3 • TRAM1

Mezigdomide (MEZI) in Novel Combinations Effectively Reactivates Immune System in Patients with Relapsed/refractory Multiple Myeloma (RRMM) Including Those After T-cell–redirecting Therapies (TCRT) (IMS 2025) - "MEZI+dexamethasone (MEZId) combined with novel agents, such as tazemetostat (TAZ), the bromodomain inhibitor (BETi) BMS-986158, and trametinib (TRAM) showed promising efficacy and safety in the phase 1/2 CA057-003 trial in pts with RRMM, including pts post-TCRT...Last regimen included TCRT (n=28: BCMA CAR-T, n=8; GPRC5D CAR-T, n=6; BCMA TCE, n=3; GPRC5D TCE, n=8, BCMA TCE+GPRC5D TCE, n=2; trispecific T-cell–activating constructs, n=1), or various non-TCRT regimens (n=28)... MEZId-based novel regimens lead to activation of adaptive and innate immune populations in pts with RRMM regardless of prior TCRT exposure. Dynamics of immune changes with MEZId-based novel regimens agree with MEZId backbone data. Results suggest prior TCRT exposure and addition of novel agents do not affect the ability of MEZI to increase activation and proliferation of NK and T cells, supporting its use in combinations for pts with prior TCRT exposure."

Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • B3GAT1 • CCR7 • CD8 • HAVCR2 • IKZF1 • IL2RA • IL7R

Targeting EZH2 and EGFR Therapeutic Vulnerabilities of TNBC with a Single Chemical Entity Confers Preclinical Treatment Advantage. (PubMed, Mol Ther) - "SAR driven optimized lead molecule S-023-0996 (41a) proficiently binds and inhibits dual targets dampening tumor cell proliferation, migration and invasion in vitro with superior efficacy and safety than individual drug combinations (EZH2 inhibitor, Tazemetostat and EGFR inhibitor, Gefitinib). S-023-0996 has favourable pharmacokinetic properties and inhibits tumor growth and metastasis in vivo more efficiently than comparator drug combinations in preclinical TNBC models. Our results represent the discovery of first-in-class dual EZH2-EGFR inhibitor and establish the possibility of targeting two vulnerabilities of TNBC together with a single chemical entity."

IO biomarker • Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PARP1 • PD-1 • PD-L1

Proof-of-concept study in patient-derived organoids from malignant pleural effusion for functional testing in thoracic tumors. (PubMed, Biomed Pharmacother) - "Candidate hits like Idarubicin, Tazemetostat or Vemurafenib were further examined through dose-response assays. These findings demonstrate the feasibility of generating patient-derived organoids from malignant pleural effusions and support their use as exploratory platforms for functional drug testing in thoracic malignancies. Further studies with larger cohorts and integrated molecular analyses are required to validate their potential clinical utility."

IO biomarker • Journal • Pleural effusion • Lung Adenocarcinoma • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Pleural Mesothelioma • Respiratory Diseases • Solid Tumor • Thoracic Cancer