HEMATOLOGIC MALIGNANCIES—LYMPHOMA AND CHRONIC LYMPHOCYTIC LEUKEMIA

7500 Oral Abstract Session

Glofitamab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma
(DLBCL) and ≥ 2 prior therapies: Pivotal phase II expansion results.

Michael Dickinson, Carmelo Carlo-Stella, Franck Morschhauser, Emmanuel Bachy, Paolo Corradini,
Gloria Iacoboni, Cyrus Khan, Tomasz Wrobel, Fritz Offner, Marek Trneny, Shang-Ju Wu, Guillaume
Cartron, Mark Hertzberg, Anna Sureda Balari, David Perez-Callejo, Linda Lundberg, James Relf,
Emma Clark, Kathryn Humphrey, Martin Hutchings; Peter MacCallum Cancer Centre, Royal Mel-
bourne Hospital and The University of Melbourne, Melbourne, Australia; Humanitas University and
IRCCS Humanitas Research Hospital, Milan, Italy; Ho^pital Claude Huriez and CHU de Lille, Lille,
France; Centre Hospitalier Lyon-Sud, Lyon, France; Universita� degli Studi di Milano and Fondazione
Istituti di Ricovero e Cura a Carattere Scientifico (IRCSS) Istituto Nazionale dei Tumori, Milan, Italy;
Vall d�Hebron University Hospital, Barcelona, Spain; Allegheny Health Network, Pittsburgh, PA; Uni-
wersytet Medyczny we Wrocławiu, Wroclaw, Poland; Universitair Ziekenhuis Gent, Ghent, Belgium;
Charles University Hospital, Prague, Czech Republic; National Taiwan University Hospital, Taipei, Tai-
wan; CHU de Montpellier, Montpellier, France; Prince of Wales Hospital and University of New South
Wales, Sydney, NSW, Australia; Institut Catala� d’Oncologia – Hospitalet, IDIBELL, University of Barce-
lona, Barcelona, Spain; F. Hoffmann-La Roche Ltd., Basel, Switzerland; Roche Products Ltd, Welwyn
Garden City, United Kingdom; Rigshospitalet, Copenhagen, Denmark

Background: Glofitamab is a T-cell engaging bispecific antibody (Ab) with a novel 2:1 configuration
that confers bivalency for CD20 (B cells) and monovalency for CD3 (T cells). In a Phase I/II study
(NCT03075696), escalating glofitamab doses were highly active and well tolerated in pts with R/R B-
cell lymphomas, with obinutuzumab pretreatment (Gpt) and Cycle (C) 1 step-up dosing providing ef-
fective CRS mitigation. For the first time, we present pivotal Phase II expansion results in pts with R/R
DLBCL and ≥2 prior therapies. Methods: All pts had DLBCL (DLBCL NOS, HGBCL, PMBCL, or trFL)
and had received ≥2 prior regimens including ≥1 anti-(a) CD20 Ab and ≥1 anthracycline. IV Gpt
(1000mg) was given 7 days before the first glofitamab dose. IV glofitamab was then given as step-up
doses on Day (D) 1 (2.5mg) and D8 (10mg) of C1 and at the target dose (30mg) on D1 of C2–12 (21-
day cycles). The primary endpoint was CR rate (best response during initial treatment) assessed by In-
dependent Review Committee (IRC) using Lugano 2014 criteria. CRS was assessed using ASTCT crite-
ria. Results: As of Sep 14, 2021, 107 pts had received ≥1 dose of study treatment (median age: 66 yrs
[21–90]; Ann Arbor stage III–IV disease: 74%; IPI score ≥3: 54%; DLBCL NOS: 74%). Median prior
therapies was 3 (2–7); 59% had ≥3 prior therapies and 35% had received prior CAR T-cells (CAR-Ts).
Most pts were refractory to a prior aCD20 Ab-containing regimen (85%) and to their most recent regi-
men (85%). Many were refractory to their initial therapy (59%) and to prior CAR-Ts (32%). After a me-
dian follow-up of 9 months (0.1–16), ORR and CR rates by IRC were 50.0% and 35.2%, respectively.
CR rates were consistent in pts with and without prior CAR-Ts (32% vs 37%). Median time to CR was
42 days (95% CI: 41–48). The majority of CRs (33/38; 87%) were ongoing at data cut. An estimated
84% of complete responders and 61% of responders remained in response at 9 months. At data cut,
the projected 12-month OS rate was 48%, and 92% of complete responders were alive. These results
are consistent with earlier Phase I data in 100 pts treated with target glofitamab doses ≥10mg (CR
rate: 34%; estimated 20-month CR rate in complete responders: 72%). CRS occurred in 68% of pts,
was primarily associated with the initial doses, and was mostly Gr 1 (51%) or Gr 2 (12%); Gr 3 (3%)
and Gr 4 (2%) events were uncommon. All but 2 CRS events were resolved at data cut. Glofitamab-re-
lated neurologic AEs potentially consistent with ICANS occurred in 3 pts (all Gr 1–2). No glofitamab-
related Gr 5 (fatal) AEs occurred. Glofitamab-related AEs leading to discontinuation were uncommon
(3 pts, 3%). Conclusions: Fixed-duration glofitamab induces durable complete remissions and has fa-
vorable safety in pts with R/R DLBCL and ≥2 prior therapies, including those with prior exposure to
CAR-Ts. Glofitamab is a promising new therapy for pts with heavily pretreated and/or highly refractory
DLBCL. Clinical trial information: NCT03075696. Research Sponsor: Third-party medical writing as-
sistance, under the direction of all authors, was provided by Scott Malkin of Ashfield MedComms, an
Ashfield Health company, and was funded by F. Hoffmann-La Roche Ltd.

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