Abstract 1639P
Background
TAZ, a first-in-class EZH2 inhibitor, is the only FDA-approved treatment for epithelioid sarcoma (ES) and is under review for approval for follicular lymphoma (FL). We analyzed adverse events (AEs) from clinical trials of single-agent TAZ in a larger population of pts with hematologic malignancies and genetically defined tumors.
Methods
Treatment-emergent AEs (TEAEs) were compiled from 6 studies. The analysis cohort included pts ≥18 yrs who had received ≥1 dose of TAZ 800 mg BID. TEAEs are reported descriptively.
Results
Safety was assessed in 690 pts with non-Hodgkin lymphoma (n=358, including FL [n=109]), ES (n=104), and other solid tumors (n=228). Median drug exposure was 3.5 (range, 0.02–52.2) mos; 605 (88%) pts completed ≥90% of the planned dose. TEAEs led to dose reduction in 30 (4%) pts, drug interruption in 220 (32%), and drug discontinuation in 40 (6%). The most common TEAEs were nausea, fatigue, and vomiting observed early in treatment (≤4 mos). Grade 3–4 TEAEs were reported in 359 (52%) pts; 126 (18%) were assessed as drug-related. Five pts (4 with primary lymphomas) had AEs of special interest per protocol (acute myeloid leukemia [AML], n=2; myelodysplastic syndrome [MDS], n=2; MDS to AML transformation, n=1); these were confounded by prior treatments and baseline hematologic abnormalities. One pediatric chordoma pt (900 mg/m2 BID for 15 mos) excluded from this analysis of adults had a secondary T-cell lymphoblastic lymphoma. Two pts died of related TEAEs (intestinal obstruction and reason unknown) during or ≤30 days after treatment. The overall safety profile was similar in pts with hematologic vs solid tumors, with differences attributed to underlying disease and/or comorbidities. Table: 1639P
| All TEAEs∗ N=690 | Treatment-related TEAEs N=690 | |||
| All grades | Grade 3–4 | All grades | Grade 3–4 | |
| Pts with TEAEs, n (%) | 661 (96) | 359 (52) | 455 (66) | 126 (18) |
| Adverse event, n (%) | ||||
| Nausea | 186 (27) | 8 (1) | 127 (18) | 5 (0.7) |
| Fatigue | 164 (24) | 16 (2) | 107 (16) | 7 (1) |
| Vomiting | 136 (20) | 6 (1) | 54 (8) | 3 (0.4) |
| Diarrhea | 120 (17) | 7 (1) | 54 (8) | 5 (0.7) |
| Cough | 118 (17) | 1 (0.1) | 15 (2) | 0 |
| Anemia | 114 (17) | 54 (8) | 62 (9) | 28 (4) |
| Decreased appetite | 105 (15) | 7 (1) | 52 (8) | 1 (0.1) |
| Thrombocytopenia | 77 (11) | 38 (6) | 54 (8) | 23 (3) |
| Neutropenia | 51 (7) | 40 (6) | 41 (6) | 29 (4) |
∗TEAEs occurring in ≥15% of pts and grade 3–4 TEAEs occurring in ≥5% of pts are shown. TEAEs were defined as adverse events that started or worsened on or after the day of the first TAZ dose up to 30 days after the last dose.
Conclusions
The most common TEAEs were mild/moderate and resolved with standard medical care and/or dose modification. Dose reductions/discontinuations due to TEAEs were uncommon. TAZ was generally well tolerated with an overall safety profile consistent across indications..
Clinical trial identification
NCT01897571, NCT03010982, NCT03028103, NCT02601950, NCT02860286, NCT02875548.
Editorial acknowledgement
Third-party writing assistance was provided by Sabrina Hom, PhD, of Ashfield Healthcare Communications, part of UDG Healthcare plc, and funded by Epizyme, Inc.
Legal entity responsible for the study
Epizyme, Inc.
Funding
Epizyme, Inc.
Disclosure
F. Morschhauser: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Janssen; Advisory/Consultancy: Celgene; Advisory/Consultancy: Bayer; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Verasteem; Advisory/Consultancy: Gilead; Advisory/Consultancy: Servier; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Epizyme. P. McKay: Honoraria (self), Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Gilead; Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Advisory/Consultancy: Epizyme. G. Salles: Advisory/Consultancy: Abbvie, Amgen, Autolus, Celgene, Gilead, Epizyme, Janssen, Karyopharm, Kite, Merck, Morphosys, Novartis, Roche, Servier, and Takeda. S. Stacchiotti: Research grant/Funding (self): Epizyme and Eli Lilly; Research grant/Funding (institution): Epizyme, Novartis, and Eli Lilly. G.K. Schwartz: Travel/Accommodation/Expenses: AbbVie Inc SHS, Astex Pharmaceuticals, Incyte, Merck, Calithera Biosciences, Lilly, Novartis, Fortress, Darwin Health, Human Longevity, Inc, Bionaut Labs, PureTech, Ellipses Pharma, Array BioPharma, PTC Therapeutics, Bayer, Iovance Biotherapeutics, Pfizer; Travel/Accommodation/Expenses: PureTech, Array BioPharma, PTC Therapeutics, Iovance Biotherapeutics, Pfizer, Abbott, Becton Dickinson, Merck and Co Inc Shs, Johnson and Johnson, Glaxosmithkline Plc adr., Fortress Biotech, Bristol-Myers Squibb, Daiichi Sankyo; PureTech, Darwin Health,. H. Tilly: Honoraria (self): Merck and Servier ; Advisory/Consultancy: Roche/Genentech, Janssen, and Karyopharm. M.G. Zauderer: Advisory/Consultancy: Epizyme, Aldeyra Therapeutics, Novocure, Atara Biotherapeutics; Honoraria (self): Medical Learning Institute; Research grant/Funding (self): MedImmune, Epizyme, Polaris, Sellas Life Sciences, Bristol-Myers Squibb, Millennium, Curis, GlaxoSmithKline. D.A. Fennell: Honoraria (self): Inventiva; Advisory/Consultancy: Inventiva, Atara, Aldeyra; Speaker Bureau/Expert testimony: Astra Zeneca, Roche; Research grant/Funding (self): Bayer, Astex, Boehringer Ingelheim; Travel/Accommodation/Expenses: MSD, BMS. R.L. Jones: Research grant/Funding (self): MSD, Adaptimmune, Blueprint, Clinigen, Eisai, Epizyme, Daiichi, Deciphera, Immunedesign, Lilly, Merck, Pharmamar, Tracon, and UptoDate. P. Schöffski: Research grant/Funding (self): Deciphera; Research grant/Funding (institution): Exelixis, Plexxikon, Eisai, Loxo, Eli Lilly, Blueprint Medicines, Ellipses Pharma, Deciphera, Merck, Servier, Genmab, Adaptimmune, Intellisphere, and Transgene. T. Phillips: Research grant/Funding (self): Pharmacyclics, AbbVie; Advisory/Consultancy: Genentech, Gilead, Bayer, Seattle Genetics, and Pharmacyclics. A. Chaidos: Honoraria (self): Celgene, Takeda, Gilead, and Janssen. V. Villalobos: Research grant/Funding (self): Epizyme, Eli Lilly, Nanocarrier, Agios Pharmaceuticals, Daiichi, Novartis, Janssen, Springworks, Abbvie, and Blueprint Medicines. G. Demetri: Research grant/Funding (self): Epizyme, Novartis, Bayer, Pfizer, Loxo Oncology, AbbVie, Daiichi-Sankyo, Adaptimmune, GlaxoSmithKline, Janssen, PharmaMar, Roche/Genentech, Ignyta, Epizyme, Novartis, Bayer, Pfizer, EMD-Serono, Sanofi, Loxo Oncology, AbbVie, Mirati Therapeutics, Daiichi-S; Shareholder/Stockholder/Stock options: Epizyme, Novartis, Bayer, Pfizer, EMD-Serono, Loxo Oncology, Daiichi-Sankyo, WIRB Copernicus Group, M.J. Hennessey/OncLive, Adaptimmune, Blueprint Medicines, Merrimack Pharmaceuticals, G1 Therapeutics, CARIS Life Sciences, Bessor Pharmaceuticals, ERASCA P; Non-remunerated activity/ies: Epizyme, Novartis, AbbVie, Daiichi-Sankyo, PharmaMar, and Roche/Genentec. G. Cote: Research grant/Funding (self): Epizyme, PharmaMar, and Agios; Non-remunerated activity/ies: PharmaMar, Eisai, and the Merck KGaA/EMD Serono Research and Development Institute; Research grant/Funding (institution): Epizyme, PharmaMar, Agios, Otsuka, Amgen, Eisai, Macrogenics, Boston Biomedical, Plexxicon, the Merck KGaA/EMD Serono Research and Development Institute, CBA, SpringWorks Therapeutics, Bavarian-Nordic, Aileron Therapeutics, and Bayer. L. Sierra, J. Yang, P. Slatcher, S. Agarwal: Shareholder/Stockholder/Stock options: Epizyme. M. Gounder: Advisory/Consultancy: Epizyme, Karyopharm, Daiichi; Honoraria (self): Karyopharm, Daiichi, Tracon Pharmaceuticals, and Amgen; Travel/Accommodation/Expenses: Epizyme.