PHASE'2'MULTICENTER'STUDY'OF'TAZEMETOSTAT,'AN'EZH2'INHIBITOR,'IN'
PATIENTS'WITH'RELAPSED'OR'REFRACTORY'FOLLICULAR'LYMPHOMA'
POSTER'37'
''
Franck! Morschhauser1,! Hervé! Tilly2,! Aristeidis! Chaidos3,! Tycel! Phillips4,! Vincent! Rigbrag5,! Philip!
Campbell6,! Gandhi! Laurent! Damaj7,! Wojciech! Jurczak8,! Pamela! McKay9,! Stephen! Opat10,! John!
Radford11,!Jennifer!Whalen12,!Anand!Rajarethinam12,!Deyaa!Adib12!and!Gilles!Salles13!
!
(1)CHRU!de!Lille,!Lille,!France,!(2)Centre!Henri!Becquerel,!Rouen!University,!Rouen,!France,!(3)Centre!
for!Haematology,!Department!of!Medicine,!Imperial!College!London,!Imperial!College!Healthcare!NHS!
Trust,! Hammersmith! Hospital,! London,! United! Kingdom,! (4)Division! of! Hematology! and! Oncology,!
University! of! Michigan,! Ann! Arbor,! (5)Gustave! Roussy,! Villejuif,! France,! (6)Barwon! Health,! Geelong,!
Australia,! (7)Hematology! Institute! University! Hospital! School! of! Medicine,! Caen,! France,! (8)Maria!
SklodowskaUCurie! National! Research! Institute! of! Oncology,! Krakow,! Poland,! (9)Beatson! West! of!
Scotland!Cancer!Centre,!Glasgow,!United!Kingdom,!(10)School!of!Clinical!Sciences!at!Monash!Health,!
Monash!University,!Victoria,!Australia,!(11)NIHR!Manchester!Clinical!Research!Facility,!University!of!
Manchester!and!the!Christie!NHS!Foundation!Trust,!Manchester,!United!Kingdom,!(12)Epizyme,!Inc.,!
Cambridge,!(13)Lymphoma!Service,!Memorial!Sloan!Kettering!Cancer!Center,!New!York!
!
Objectives:!As! many! patients! with! follicular! lymphoma! (FL)! eventually! progress,! there! is! a!
need!for!efficacious!and!tolerable!treatments,!especially!for!those!with!highJrisk!disease!who!
progress! within! 24! months! of! diagnosis! (POD24).! EZH2,! an! epigenetic! regulator! of! gene!
expression! and! cell! fate! decisions,! is! ubiquitous! to! all! FL! tumors! and! contributes! to! their!
growth! and! survival.! Tazemetostat,! a! firstJinJclass! selective! oral! EZH2! inhibitor,! has!
demonstrated! durable,! singleJagent! antitumor! activity! in! relapsed/refractory! (R/R)! FL!
patients!with!wildJtype!(WT)!or!mutant!(MT)!EZH2.!We!report!efficacy!and!safety!data.!
Methods:!This!openJlabel,!multicenter!phase!2!study!(NCT01897571)!evaluated!twiceJdaily!
oral!tazemetostat!800!mg!in!adults!with!WT!or!MT!EZH2!R/R!FL!(grade!1J3b).!Patients!had!
ECOG! performance! status! 0–2,! ≥2! prior! treatment! regimens,! and! measurable! disease.! The!
primary!endpoint!was!objective!response!rate!(ORR).!Secondary!endpoints!included!duration!
of! response! (DOR),! progressionJfree! survival! (PFS),! and! safety.! The! POD24! subgroup! was!
composed! of! patients! experiencing! disease! progression! or! relapse! within! 24! months! of!
diagnosis!or!at!the!start!of!frontJline!treatment!with!immunochemotherapy.!
Results:!The!study!enrolled!99!patients!(WT!EZH2,!n=54!POD24,!n=32;!59%;!MT!EZH2,!n=45!
POD24,! n=19;! 42%).! The! ORR! (95%! confidence! interval! CI)! was! 35%! (22.7–49.4)! in! the!
WT!EZH2!cohort!and!69%!(53.4–81.8)!in!the!MT!EZH2!cohort!(Table).!Median!(95%!CI)!DOR!
was!13.0!(5.6–not!estimable!NE)!months!in!the!WT!EZH2!cohort!(n=19)!and!10.9!(7.2–NE)!
months!in!the!MT!EZH2!cohort!(n=31).!The!median!(95%!CI)!PFS!was!11.1!(3.7–14.6)!months!
and!13.8!(10.7–22.0)!months!in!the!WT!and!MT!EZH2!cohorts,!respectively.The!ORR!(95%!CI)!
for!the!POD24!subgroup!was!25%!(11.5–43.4)!in!the!WT!EZH2!cohort!and!63%!(38.4–83.7)!in!
the! MT!EZH2!cohort.! These! results! demonstrate! the! potent! antitumor! activity! of!
tazemetostat,! regardless! of! prognostic! category.! The! most! common! treatmentJrelated! allJ
grade!treatmentJemergent!adverse!events!(TEAEs)!were!nausea!(19%)!and!asthenia!(15%).!
The!most!frequently!reported!treatmentJrelated!grade!≥3!TEAEs!included!thrombocytopenia!
(3%),! anemia! (2%),! asthenia! (1%),! and! fatigue! (1%).! Among! all! patients,! 8%! discontinued!
treatment!and!9%!had!dose!reductions!because!of!TEAEs.!No!treatmentJrelated!deaths!were!
reported.!
Conclusion:!Tazemetostat!was!generally!well!tolerated,!with!a!low!incidence!of!treatmentJ
related! grade! ≥3! TEAEs.! Tazemetostat! demonstrated! clinically! meaningful,! durable,! singleJ