The DOI matches its Crossref record.
Phase 2, multicenter study of the EZH2 inhibitor tazemetostat as monotherapy in adults with relapsed or refractory (R/R) malignant mesothelioma (MM) with BAP1 inactivation.
Abstract
8515 Background: MM often presents at an advanced stage with a median survival of ~1 year. Treatments are limited; none clearly improve survival in second-line. In 40–60% of MM patients (pts) BRCA1 associated protein 1 (BAP1) is inactive and linked to a dependency on EZH2 (enhancer of zeste-homolog 2). EZH2 regulates gene expression to prevent differentiation of stem and progenitor cells, and aberrant EZH2 activity is implicated as an oncogenic driver. Tazemetostat, a potent, selective, oral EZH2 inhibitor demonstrated clinical activity in other malignancies; here we report preliminary data in inactive BAP1 MM. Methods: This is a phase 2, multicenter, open-label, single-arm study of tazemetostat (800 mg po BID) in pts with measurable R/R MM. PK and safety were assessed in a cohort of 13 pts. Efficacy was assessed via a 2-stage Green Dahlberg design in 61 pts with inactive BAP1 with a primary endpoint of 12-week disease control rate [DCR; CR or PR + SD]. Response was evaluated every 6 weeks with modified RECIST and/or RECIST 1.1. Secondary endpoints included ORR, PFS, OS, safety, population PK and response biomarkers (RNAseq, immunomodulation, exploratory prognostic indices). Results: Enrollment is complete (N = 74). Disease characteristics were typical of MM with the exception of a bias towards epithelioid histology (88%) that has a higher incidence of BAP1 inactivation. All pts had ≥1 prior systemic therapy. No pts discontinued due to AEs; however, 5 pts had dose reductions due to AEs. Fatigue (32%), decreased appetite (28%), dyspnea (28%), and nausea (27%) were the most frequently reported AEs of any grade regardless of attribution. In the efficacy portion of the study, the Stage 2 DCR criterion of ≥35% was surpassed, with 31 pts (51%) achieving disease control at 12 weeks and 15 pts (25%) sustained disease control at 24 weeks, 5 of whom are ongoing. Two of 61 patients had a confirmed partial response. Conclusions: Tazemetostat monotherapy shows promising antitumor activity, including confirmed responses and long-term disease control, with favorable safety/tolerability in pts with MM. These results support further evaluation of tazemetostat in pts with MM. Clinical trial information: NCT02860286.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Targeting DOT1L can impact the progression of MLL fusion-protein leukaemia.
“providing proof of concept that targeting DOT1L can impact the progression of this aggressive disease 170 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [170]
Citations
Cited by
Sorted by citations
The roles of DNA, RNA and histone methylation in ageing and cancer
Michalak, E. M., Burr, M. L., Bannister, A. J., & Dawson, M. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0143-1 · Cited by 549
Targeting epigenetic modifications in cancer therapy: erasing the roadmap to cancer
Mohammad, H. P., Barbash, O., & Creasy, C. L. (2019) · Nature Medicine · doi:10.1038/s41591-019-0376-8 · Cited by 424
Hoy, S. M. (2020) · Drugs · doi:10.1007/s40265-020-01288-x · Cited by 340
“Key clinical trials of tazemetostat Drug(s) Indication Phase Status Location(s) Identifier Sponsor Tazemetostat, atezolizumab, obinutuzumab Relapsed/refractory FL and DLBCL I Completed Multinational NCT02220842 Hoffmann-La Roche Tazemetostat Relapsed or refractory INI1negative tumours or SS I Recruiting Multinational…”
BackgroundInfluentialEZH2-Targeted Therapies in Cancer: Hype or a Reality
Eich, M., Athar, M., Ferguson, J. E., & Varambally, S. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-2147 · Cited by 254
Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease
Bhat, K. P., Kanıskan, H. Ü., Jin, J. J., & Gozani, O. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-00108-x · Cited by 250
BAP1: Not just a BRCA1-associated protein
Louie, B. H., & Kurzrock, R. (2020) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2020.102091 · Cited by 198
“[63] These results show support for the potential targeted use of EZH2 inhibitors in BAP1mutated cancers.”
ResultPerspectives on the Treatment of Malignant Pleural Mesothelioma
Janes, S. M., Alrifai, D., & Fennell, D. A. (2021) · New England Journal of Medicine · doi:10.1056/nejmra1912719 · Cited by 193
Self-citationRecent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends
Nepali, K., & Liou, J. (2021) · Journal of Biomedical Science · doi:10.1186/s12929-021-00721-x · Cited by 187
Nicholson, A. G., Sauter, J. L., Nowak, A. K., Kindler, H. L., Gill, R. R., Rémy‐Jardin, M., Armato, S. G., Fernandez‐Cuesta, L., Bueno, R., Alcala, N., et al. (2019) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2019.08.2506 · Cited by 167
Self-citationAdvances in epigenetic therapeutics with focus on solid tumors
Jin, N. Y., George, T. L., Otterson, G. A., Verschraegen, C. F., Wen, H., Carbone, D. P., Herman, J. G., Bertino, E. M., & He, K. (2021) · Clinical Epigenetics · doi:10.1186/s13148-021-01069-7 · Cited by 135
Rugo, H. S., Jacobs, I. A., Sharma, S., Scappaticci, F. A., Paul, T. A., Jensen-Pergakes, K., & Malouf, G. G. (2020) · Advances in Therapy · doi:10.1007/s12325-020-01379-x · Cited by 108
“A phase 2 study of tazemetostat in patients with relapsed/refractory (r/r) malignant mesothelioma with BAP1 inactivation (NCT02860286) has also reported favorable safety and tolerability, and promising antitumor activity [60].”
BackgroundMalignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future
Nicolini, F., Bocchini, M., Bronte, G., Delmonte, A., Guidoboni, M., Crinò, L., & Mazza, M. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2019.01519 · Cited by 83
“A phase II clinical trial (NCT02860286) is ongoing to evaluate the efficacy of the EZH2 inhibitor tazemetostat in MPM patients [61].”
BackgroundPBRM1, SETD2 and BAP1 — the trinity of 3p in clear cell renal cell carcinoma
Walton, J., Lawson, K. A., Prinos, P., Finelli, A., Arrowsmith, C. H., & Ailles, L. (2022) · Nature Reviews Urology · doi:10.1038/s41585-022-00659-1 · Cited by 71
Emerging Treatments for Malignant Pleural Mesothelioma: Where Are We Heading?
Cantini, L., Hassan, R., Sterman, D. H., & Aerts, J. G. J. V. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00343 · Cited by 59
“EZH inhibition may then represent a promising strategy, with tazemetostat showing a promising disease control rate of 51% at 12 weeks in amulticenter phase 2 trial (64).”
BackgroundBAP1: role in carcinogenesis and clinical implications
Kobrinski, D., Yang, H., & Kittaneh, M. (2020) · Translational Lung Cancer Research · doi:10.21037/tlcr.2019.11.24 · Cited by 48
“The disease control of tazemetostat was 51% at 12 weeks and 25% of patients-maintained disease control at 24 weeks (17).”
BackgroundBAP1 Tumor Predisposition Syndrome
Smith, S. M., Abdel‐Rahman, M. H., Pilarski, R., Davidorf, F. H., & Cebulla, C. M. (2021) · Springer eBooks · doi:10.1007/978-3-030-78117-0_3 · Cited by 31
Emerging therapies in malignant pleural mesothelioma
Cinausero, M., Rihawi, K., Cortiula, F., Follador, A., Fasola, G., & Ardizzoni, A. (2019) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2019.102815 · Cited by 23
“No patients discontinued treatment due to adverse events [98].”
BackgroundMola, S., Pinton, G., Erreni, M., Corazzari, M., Andrea, M. D., Grolla, A. A., Martini, V., Moro, L., & Porta, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094391 · Cited by 27
“, Cambridge, MA, USA) has been recently approved by FDA for patients with advanced epithelioid sarcoma [18] and has also entered into clinical trials for diffuse large B-cell lymphoma [19], follicular lymphoma [20], and relapsed or refractory MPM with BRCA1 associated protein 1 (BAP1) inactivation [21,22].”
BackgroundDudnik, E., Bar, J., Moore, A., Gottfried, T., Moskovitz, M. T., Dudnik, J., Shochat, T., Allen, A. M., Zer, A., Rotem, O., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.603223 · Cited by 19
“This is based on its selective in vivo activity in BAP1-mutant MPM (57), and positive results obtained in a phase 2 trial conducted in BAP1-altered MPM (the study met its primary end point demonstrating a disease-control rate of 51% at 12 weeks) (58).”
BackgroundClinicopathologic significance of protein lysine methyltransferases in cancer
Vougiouklakis, T., Bernard, B., Nigam, N., Burkitt, K., Nakamura, Y., & Saloura, V. (2020) · Clinical Epigenetics · doi:10.1186/s13148-020-00897-3 · Cited by 18
CDKN2A Determines Mesothelioma Cell Fate to EZH2 Inhibition
Pinton, G., Wang, Z., Balzano, C., Missaglia, S., Tavian, D., Boldorini, R. L., Fennell, D. A., Griffin, M., & Moro, L. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.678447 · Cited by 16
“A phase II clinical trial (NCT02860286) of Tazemetostat (EPZ-6438), a potent and selective EZH2 inhibitor, in MPM with inactive BAP1 has shown promising results (43).”
Self-citationThe Evolving Landscape of the Molecular Epidemiology of Malignant Pleural Mesothelioma
Lettieri, S., Bortolotto, C., Agustoni, F., Lococo, F., Lancia, A., Comoli, P., Corsico, A. G., & Stella, G. M. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10051034 · Cited by 15
“, tazemetostat, EPZ-6438) decreased cell proliferation and reduced invasion and clonogenic capacity in mesothelioma cell lines and in in vivo experiments [53].”
BackgroundLian, B., Zhang, K., Fang, X.-D., Li, F., Dai, Z., Chen, W., & Qi, X.-P. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.927250 · Cited by 11
“It is interesting that several therapies targeting the BAP1 alterations showed a positive potential in cancers, according to the recent studies (21, 22).”
BackgroundResultBanna, G. L., Signori, A., Fontecedro, A. C., et al. (2022) · European Journal of Cancer · doi:10.1016/j.ejca.2022.02.030 · Cited by 10
The Evolving Therapeutic Landscape for Malignant Pleural Mesothelioma
Perera, N. D., & Mansfield, A. S. (2022) · Current Oncology Reports · doi:10.1007/s11912-022-01302-3 · Cited by 9
BAP1 regulates HSF1 activity and cancer immunity in pancreatic cancer
Yuan, W., Zhang, Q., Zhao, Y., Xia, W., Yin, S., Liang, X., Chen, T., Li, G., Liu, Y., Liu, Z., et al. (2024) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-024-03196-4 · Cited by 8
Malignant Pleural Mesothelioma: Is Tailoring the Second-Line Therapy Really “Raising the Bar?”
Noia, V. D., Vita, E., Ferrara, M. G., et al. (2019) · Current Treatment Options in Oncology · doi:10.1007/s11864-019-0616-7 · Cited by 7
“Considering the acceptable safety profile and the interesting clinical activity, tazemetostat is worthy to be evaluated in a larger clinical trial [51].”
BackgroundFunctional characterisation guides classification of novel BAP1 germline variants
Hong, J. H., Chong, S. T., Lee, P.-H., et al. (2020) · npj Genomic Medicine · doi:10.1038/s41525-020-00157-6 · Cited by 7
Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future
Nicolini, F., Bocchini, M., Bronte, G., et al. (2021) · Vide Leaf, Hyderabad eBooks · doi:10.37247/pacr.1.2021.32 · Cited by 7
Precision Therapy for Mesothelioma: Feasibility and New Opportunities
Dulloo, S., Bzura, A., & Fennell, D. A. (2021) · Cancers · doi:10.3390/cancers13102347 · Cited by 7
“Interestingly, 2 of the 61 patients had confirmed partial responses [37].”
BackgroundSelf-citationActivation of DNA Damage Tolerance Pathways May Improve Immunotherapy of Mesothelioma
Brossel, H., Fontaine, A., Hoyos, C., Jamakhani, M., Willems, M., Hamaïdia, M., & Willems, L. (2021) · Cancers · doi:10.3390/cancers13133211 · Cited by 6
“Clinical evidence for efficacy of an EZH2 inhibitor (Tazemetostat) was observed in a multicenter phase 2 trial on relapsed or refractory MM with BAP1 inactivation [14].”
BackgroundFan, K., Zhang, C., Zhang, B.-H., Gao, M., & Sun, Y.-C. (2022) · Scientific Reports · doi:10.1038/s41598-022-21005-w · Cited by 6
Fennell, D. A., Griffiths, D., Eminton, Z. B., et al. (2023) · BMJ Open · doi:10.1136/bmjopen-2023-073120 · Cited by 5
Self-citationThe therapeutic implications of the genomic analysis of malignant pleural mesothelioma
Zauderer, M. G. (2021) · Nature Communications · doi:10.1038/s41467-021-22142-y · Cited by 5
Self-citationBAP1 Tumor Predisposition Syndrome
Segura, R. N. L., & Hoang, M. P. (2025) · Advances in Anatomic Pathology · doi:10.1097/pap.0000000000000507 · Cited by 4
Zahiu, T., Mihu, C. M., Boşca, A. B., Mărginean, M. V., Mocan, L. P., Lupean, R.-A., Suflețel, R. T., Mihu, C., & Melincovici, C. S. (2025) · Diagnostics · doi:10.3390/diagnostics15111323 · Cited by 3
“In a phase 2 trial by Zauderer et al. [139], Tazemetostat (Tazverik) was given to 61 patients, but only 2 showed a partial response.”
Novel and Promising Systemic Treatment Approaches in Mesothelioma
Dudnik, E., Reinhorn, D. J., & Holtzman, L. (2021) · Current Treatment Options in Oncology · doi:10.1007/s11864-021-00883-8 · Cited by 3
Offin, M. D., Rusch, V. W., Rimner, A., Adusumilli, P. S., & Zauderer, M. G. (2022) · The Oncologist · doi:10.1093/oncolo/oyac113 · Cited by 3
Self-citationHistone Modifying Enzymes as Targets for Therapeutic Intervention in Oesophageal Adenocarcinoma
Pickering, O. J., Breininger, S. P., Underwood, T., & Walters, Z. S. (2021) · Cancers · doi:10.3390/cancers13164084 · Cited by 2
“Tazemetostat, an oral SAM-competitive inhibitor, was licensed by the FDA in 2020 for paediatric and adult locally advanced or metastatic epithelioid sarcoma [21], and has also shown promising anti-tumour results in a Phase 2 clinical trial in refractory metastatic mesothelioma [78].”
BackgroundFully Human Antibodies for Malignant Pleural Mesothelioma Targeting
Nicolini, F., Bocchini, M., Angeli, D., Bronte, G., Delmonte, A., Crinò, L., & Mazza, M. (2020) · Cancers · doi:10.3390/cancers12040915 · Cited by 2
“BAP1 mutational status is clearly associated with the insurgence of MPM [9,10,12–15], the response to chemotherapy [16], patient survival [17], and, when coupled to other DNA repair gene alterations, it has suggested synthetic lethality therapeutic approaches [18,19].”
BackgroundAsbestos and the Pathophysiology of Mesothelioma
van Zandwijk, N., & Reid, G. (2019) · Springer eBooks · doi:10.1007/978-3-030-16884-1_2 · Cited by 2
Emerging Drug Therapies for Mesothelioma
Oien, D. B., CHIEN, J. R., Molina, J. R., & Shridhar, V. (2020) · IntechOpen eBooks · doi:10.5772/intechopen.91752 · Cited by 2
“benefiting long-term disease control [47].”
Real-world immunotherapy outcomes in unresectable peritoneal mesothelioma: A French experience
Smolenschi, C., Boilève, A., Vaflard, P., Watson, S., Sourouille, I., Valéry, M., Hollebecque, A., Lion, M., Anglaret, S., Camilleri, G. M., et al. (2025) · European Journal of Cancer · doi:10.1016/j.ejca.2025.116066 · Cited by 1
Hong, J. H., Yong, C. H., Heng, H. L., Yao, X., Li, Z., Sun, Y., Wang, P., Xiao, R., Wang, L. C., Chen, J., et al. (2026) · Science Translational Medicine · doi:10.1126/scitranslmed.adr6668 · Cited by 2
The Immune System of Mesothelioma Patients: A Window of Opportunity for Novel Immunotherapies
Nicolini, F., & Mazza, M. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.98617 · Cited by 1
Johnson, B., Lee, K. M. L., & Cheng, Y. Y. (2021) · Onco · doi:10.3390/onco1020006 · Cited by 1
Epigenetic therapies—update on lysine methyltransferase/PRC complex inhibitors
Kim, S., Barkey, N. M., Atasoylu, O., & Dhanak, D. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91367-6.00011-8 · Cited by 1
Bátai, B., Lévai, D., Weisinger, J., Balogh, A., Gángó, A., Bödör, C., & Nagy, N. (2018) · Hematológia–Transzfuziológia · doi:10.1556/2068.2018.51.2.3
Fennell, D. A. (2021) · Respiratory disease series · doi:10.1007/978-981-15-9158-7_24
Self-citationClinical utility of solid tumor epigenetics
Demirdizen, E., Taranda, J., & Turcan, Ş. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-823928-5.00013-x
Sun, Y., Fan, K., Zhang, C., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1295410/v1
Maciá, S. (2020) · IntechOpen eBooks · doi:10.5772/intechopen.89396
Systemic Treatments for Unresectable Pleural Mesothelioma: A Review of the Literature
Kim, F., & Addeo, A. (2021) · healthbook TIMES Oncology Hematology · doi:10.36000/hbt.oh.2021.07.027
Danlos, F. (2021) · theses.fr (ABES) · doi:10.70675/ff8cb58bzc391z43f8zbd32zc8c4b2cdc725
Metadata
- Authors
- Zauderer, M. G., Szlosarek, P., Le Moulec, S., Popat, S., Taylor, P., Planchard, D., Scherpereel, A., Jahan, T., Koczywas, M., Forster, M., Cameron, R. B., Peikert, T., Campbell, C., Sapir, I., McDonald, A., Oei, C., Clawson, A., Roche, M., & Fennell, D. A.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- St Bartholomew's Hospital (GB)
- Institut Bergonie, Bordeaux, France;
- Royal Marsden Hospital (GB)
- Manchester University NHS Foundation Trust (GB)
- Institut Gustave Roussy (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- University of California, San Francisco (US)
- City Of Hope National Medical Center (US)
- University College Hospital (GB)
- University of California, Los Angeles (US)
- Mayo Clinic (US)
- Epizyme (United States) (US)
- University of Leicester (GB)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2018-05-20
- Volume
- 36
- Issue
- 15_suppl
- Pages
- 8515-8515
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2891513328
- Cited by
- 54
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 7 · 2021: 21 · 2020: 12 · 2019: 6 · 2018: 1
- Type
- conference abstract
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Health Sciences › Medicine › Surgery › Intraperitoneal and Appendiceal Malignancies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- EZH2 inhibitors, malignant mesothelioma, relapsed/refractory disease, monotherapy, disease control rate, adverse events, pharmacokinetics, treatment response biomarkers, immunomodulation, prognostic score, epithelioid histology, second-line therapy, PD-L1 expression, PD-1/PD-L1 blockade
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
