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POLARIX: a phase 3 study of polatuzumab vedotin
plus R-CHP versus R-CHOP in patients with
untreated DLBCL
Hervé Tilly,1 Christopher Flowers,2 Jonathan W. Friedberg,3 Charles Herbaux,4
Franck Morschhauser,4 Laurie H. Sehn,5 Jeff Sharman,6 Marek Trněný,7
Calvin Lee,8 Gilles Salles9
1Centre Henri Becquerel, University of Rouen, Rouen, France; 2Winship Cancer Institute of Emory University, Atlanta, GA, USA 3University of Rochester Medical Center, Rochester, NY, USA; 4University of Lille, CHU Lille, Lille Cedex, France
5BC Cancer Agency, Vancouver, Canada; 6US Oncology and Willamette Valley Cancer Institute, Springfield, OR, USA 7Charles University, Prague, Czech Republic; 8Genentech, Inc., South San Francisco, CA, USA
9Hospices Civils de Lyon, Université Lyon-1, France
Disclosures
Hervé Tilly has received:
• Honoraria from BMS, Celgene and F. Hoffmann-La Roche Ltd
• Personal fees for consultancy and advisory board participation from Celgene, Karyopharm
and F. Hoffmann La-Roche Ltd
• Research funding from F. Hoffmann-La Roche Ltd
• Reimbursement/payment for travel/accommodation from F. Hoffmann La-Roche Ltd
R-CHOP is the frontline treatment for DLBCL
COO, cell of origin; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone 1. Vitolo U, et al. J Clin Oncol 2017;35:3529–37
An unmet need remains for patients with previously untreated DLBCL
1.0
Pro
ba
bili
ty
0 6 12 18 24 30 36 42 48 54 60
Time (months)
0.8
0.6
0.4
0.2
0R-CHOP (n=712)
PFS in patients with DLBCL receiving R-CHOP
in the GOYA trial1
3-year PFS = 66.9%
However, patients with higher risk factors, e.g. by IPI
and COO, have a poorer outcome
PF
S
Failure to improve on R-CHOP
Optimised anti-CD20More rituximab, obinutuzumab
Intensified chemotherapyR-CHOP14, DA-EPOCH-R, R-ACVBP
Maintenance therapyRituximab, everolimus, lenalidomide, enzastaurin
Novel agents in combination with R-CHOPBortezomib, ibrutinib, lenalidomide
Goy A. J Clin Oncol 2017;35:3519–22
R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone;
DA-EPOCH-R, dose-adjusted etoposide, predNisone, vincristine, cyclophosphamide, doxorubicin, and
rituximab; R-ACVBP, rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone
Polatuzumab vedotin: An ADC for DLBCL
Polatuzumab vedotin has demonstrated efficacy in R/R DLBCL in combination with rituximab1,2 and rituximab-bendamustine3
1 ADC in circulation
ADC binds to receptor2
ADC-receptor complex
is internalised3
Cytotoxic agent is released in lysosomes
4
Microtubule disruption
5
Apoptosis (cell death)6
111MMAE
Microtubule disrupter
Anti-CD79btargets to mature
B-cells
Linker
Treatment Best overall response
Pola +/- rituximab 5156%1,2
Pola + rituximab + bendamustine 68%3
ADC, antibody-drug conjugate; MMAE, monomethyl auristatin E1. Palanca-Wessels A, et al. Lancet Oncol 2015;16:70415; 2. Morschhauser F, et al. Lancet
Hematology 2019;6:e25465; 3. Sehn H, et al. Blood 2018;132:1683
Tilly H, et al. Lancet Oncol 2019; [Epub ahead of print]
77%
12%
11%
Tumour responses to pola-R-CHP assessed by PET
Complete response
Partial response
Non-responders
The safety and tolerability of pola-R-CHP is similar to that of R-CHOP1
2
G, obinutuzumab; R-CHP, rituximab, cyclophosphamide, doxorubicin, and prednisone;
R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
3 PFS in patients with 1L DLBCL receiving pola + R/G-CHP
PFS at 2 years: 83% (95%CI: 7393%)
PF
S (
%)
0 3 6 9 12 15 21 24 27 30 33
80
60
40
20
0
100
18
Pola + R/G-CHP (n=66)
In frontline: Pola-R-CHP in a phase 1b/2 trial
Months
In frontline: Pola-R-CHP in a phase 1b/2 trial
ABC, activated B cell; GCB; germinal centre B cell
4PFS by cell of origin
0
60
80
100
40
20
PF
S (
%)
0 3 27 30 336 24219 12 15 18
ABC (n=16)
GCB (n=28)
Unclassified (n=7)
Time, months
PFS by double expression of MYC and BCL2
0
60
80
100
40
20
PF
S (
%)
0 3 27 30 336 24219 12 15 18
BCL2/MYC negative (n=28)
BCL2/MYC positive (n=13)
Time, months
Tilly H, et al. Lancet Oncol 2019; [Epub ahead of print]
In frontline: Pola-R-CHP in a phase 1b/2 trial
PFS by CD79b expression
PFS (months) CD79b expression (H-score)
0 0 50 100 150 200 250 300 35001015202530
5
Tilly H, et al. Lancet Oncol 2019; [Epub ahead of print]
POLARIX: Study design
LYSA, The Lymphoma Study Association;
LYSARC, the Lymphoma Academic Research Association Collaboration with LYSA and LYSARC
Patients
• Previously untreated
DLBCL
• Age 18–80 years
• IPI 2–5
• ECOG PS 0–2
ARM A
Polatuzumab vedotin
1.8mg/kg
R-CHP + vincristine placebo
Q21D x 6 cycles
ARM B
R-CHOP + pola placebo
Q21D x 6 cycles
Rituximab
375 mg/m2
Cycles 7 and 8
Rituximab
375 mg/m2
Cycles 7 and 8
R1:1
A double-blind, phase 3, placebo-control trial
Stratification factors
• IPI score (2 vs 3–5)
• Bulky disease (≥7.5cm)
• Geographical region
N=875
POLARIX: Study objective and endpoints
*Investigator assessed; ‡These lists are not exhaustive
OBJECTIVE: To evaluate the efficacy and safety of pola + R-CHP compared with
R-CHOP in previously untreated patients with DLBCL
Primary endpoint • PFS*
Secondary
endpoints‡
• PET/CT-CR rate at end of treatment (IRC)
• Event-free survival
• Overall survival
• Patient reported outcomes
Safety endpoints‡ • Incidence, nature, and severity of adverse events
POLARIX: Treatment and assessment schedule
Cycles 1–6 Cycles 7 and 8
Drug order Dose D1 D2 D3 D4 D5 D6–21 D1
Prednisone 100 mg/day ■ ■ ■ ■ ■
Rituximab 375 mg/m2 ■ ■
Blinded polatuzumab
vedotin or placebo1.8 mg/kg ■
Blinded vincristine or
placebo
1.4 mg/m2
(max 2 mg)■
Cyclophosphamide and
doxorubicin
750 mg/m2 and
50 mg/m2 ■
• PET-CT/CT at screening, after 4 cycles and 6–8 weeks after treatment ends
• CT scans are performed every 6 months during the first two follow-up years; and then
every 12 months in years 3–5 of follow-up
POLARIX: Enrolling countries
AustriaBelgiumCzech RepublicFranceGermanyItalyPolandPortugalRussiaSpainSwitzerlandTurkeyUnited KingdomUkraine
Europe
Australia
Hong Kong
S. Korea
New Zealand
Taiwan
Japan
China
APAC
Brazil
South America
Canada
USA
North America
Conclusions
• Polatuzumab vedotin is a first-in-class anti-CD79b antibody-drug conjugate;
CD79b is ubiquitously expressed on tumour cells in patients with DLBCL
• In a phase II study, polatuzumab vedotin has exhibited clinical activity and
manageable safety profile when delivered in combination with R-CHP in
frontline DLBCL
• The POLARIX study is actively enrolling with a primary endpoint of
investigator-assessed PFS
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Acknowledgements
We would like to thank all participating patients and their families, research staff, and the investigators:
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AUSTRALIA
Uwe Hahn
Gareth Gregory
Nicholas Wickham
Sundreswran Ramanathan
Amanda Johnston
Judith Trotman
Gregory Hapgood
Mark Hertzberg
Sam Yuen
Eliza Hawkes
AUSTRIA
Philipp Staber
Daniel Heintel
Richard Greil
Martin Pecherstorfer
Ella Willenbacher
BELGIUM
Christophe Bonnet
Marie Maerevoet
Eric Straetmans
Marie-Christine Ngirabacu
Marc Andre
Ciel De Vriendt
Sylvia Snauwaert
BRAZIL
Eduardo Munhoz
Marcia Delamain
Juliana Pereira
Laura Maria Fogliatto
Nicolas Lazaretti
CANADA
Laurie Sehn
Pamela Skrabek
Michael Crump
David Macdonald
Bernard Lemieux
Jean-Francois Larouche
Carolyn Owen
Neil Chua
Isabelle Fleury
Matthew Cheung
Chrisostomos Kouroukis
CHINA
Yuqin Song
Huilai Zhang
Wei Xu
Daobin Zhou
Junning Cao
Jie Jin
Jifeng Feng
Yongping Song
Wei-Li Zhao
Dehui Zou
Yu Yang
Huiqiang Huang
Ye Guo
Liling Zhang
Wei Li
CZECH REPUBLIC
Roman Hajek
David Belada
Heidi Mocikova
Marek Trneny
Vit Prochazka
FRANCE
Corinne Haioun
Catherine Thieblemont
Hassan Fahat
Gilles Salles
Laurent Gandhi Damaj
Lucie Oberic
Laurence Sanhes
Eric Jourdan
Hervé Tilly
Frederic Peyrade
Julie Abraham
Bernard Drenou
Gianmatteo Pica
Nicolas Daguindau
Philippe Carassou
Jean Gabarre
Franck Morschhauser
Laurent Pascal
Olivier Casanovas
Pierre Feugier
Luc-Matthieu Fornecker
Hacene Zerazhi
Anne Banos
Bertrand Joly
Vincent Delwail
Krimo Bouabdallah
Anna Schmitt
Victoria Cacheux
Thierry Lamy de la Chapelle
Vincent Launay
Vincent Ribrag
Emmanuelle Nicolas-Virelizier
Marie Pierre Moles
Lysiane Molina
Jerome Cornillon
Emmanuel Gyan
Hérve Maisonneuve
Guillaume Cartron
Steven Le Gouill
David Sibon
Cecile Leyronnas
Caroline Delette
Adrien Chauchet
Ronan Le Calloch
Anne Parcelier
Katell Le Du
GERMANY
Georg Hess
Herbert Sayer
Christian Scholz
Georg Lenz
Axel Florschütz
Rudolf Weide
Andreas Hüttmann
Christian Schmidt
Thomas Weber
Sascha Dietrich
HONG KONG
Yok-Lam Kwong
Hoi-Ching Cheng
ITALY
Umberto Vitolo
Angela Giovanna Congiu
Francesco Merli
Antonio Pinto
Gianluca Gaidano
Alessandra Tucci
Alessandro Rambaldi
Maurizo Martelli
Paolo Corradini
Alberto Fabbri
JAPAN
Hiro Tatetsu
Takanori Teshima
Chihiro Yamamoto
Junichiro Yuda
Kyoya Kumagai
Emiko Sakaida
Yasuhito Terui
Kiyoshi Ando
Junya Kurodo
Hideo Koh
Kazuhito Yamamoto
Hirokazu Nagai
Takayuki Ishikawa
Tatsuo Ichinohe
Koji Kato
Koji Izutsu
Hirohiko Shibayama
Youko Suehiro
Noriko Fukuhara
Itaru Matsumura
REPUBLIC OF KOREA
Cheolwon Suh
Wonseog Kim
Jinseok Kim
Hyeon Seok Eom
Tae Min Kim
Won Sik Lee
Hojin Shin
Su-Hee Cho
NEW ZEALAND
Natalia Gavrilova
Timothy Hawkins
Peter Ganly
Allanah Kilfoyle
POLAND
Piotr Smolewski
Sebastian Grosicki
Jan Walewski
Piotr Rzepecki
Wojciech Jurczak
Tomasz Wozny
Tomasz Wrobel
PORTUGAL
Maria Gomes Da Silva
RUSSIAN FEDERATION
Olga Uspenskaya
Tatiana Chagorova
Rustem Safin
Elena Volodicheva
SPAIN
Pau Abrisqueta Costa
Juan Miguel Bergua Burgues
Javier Briones Meijide
Miguel Angel Canales Albendea
Raul Cordoba Mascuñano
Fatima De la Cruz Vicente
Eva Gonzalez Barca
Mariano Provencio Pulla
Cristina Quero Blanco
Jose Maria Arguinano Perez
Nicholas Kelleher
Armando Lopez Guillermo
Carmen Martinez Chamorro
SWITZERLAND
Klaus-Peter Schalk
Frank Stenner
Nicolas Mach
TAIWAN
Jyh-Pyng Gau
Su-Peng Yeh
Cheng-HongTsai
Yi-Chang Liu
Sheng-Yen Hsiao
TURKEY
Ahmet Burhan Ferhanoglu
Guray Saydam
Guner Hayri Ozsan
Muhit Ozcan
UKRAINE
Halyna Pylypenko
Grigoriy Rekhtman
Larysa Mykhalska
Zvenislava Maslyak
UNITED KINGDOM
Andrew McMillan
John Gribben
Fiona Miall
Tobias Menne
John Radford
Andrew Davies
Graham Collins
Moya Young
George Follows
UNITED STATES
Catherine Diefenbach
Matthew Matasar
Dipti Patel-Donnelly
Erlene Seymour
Bruce Cheson
Habte A. Yimer
Neha Mehta-Shah
John M. Burke
Craig Okada
Beth Christian
Nathalie Grover
Ian Flinn
William Houck
Miguel Islas-Ohlmayer
Alex Herrera
Abraham Kanate
Robert Emmons
Michael Meshad
Jeff-Porter Sharman
Roger Lyons
Amitkumar Mehta
Kathryn S. Kolibaba
Paolo Caimi
Herbert Eradat
Austin Kim
Christopher Flowers
Sunita Nasta
Francisco Hernandez-Ilizaliturri
Jing-Zhou Hou
Leonard Klein
Jason M. Melear
Tycel Phillips
Lode Swinnen
Gustavo Fonseca
Shachar Peles
Bertrand Anz-III
Suman Kambhampati
Faithlore Gardner
