Gilles Salles, Johannes Duell, Eva González Barca, Wojciech Jurczak,
Anna Marina Liberati, Zsolt Nagy, Aleš Obr, Gianluca Gaidano, Marc Andre,
Nagesh Kalakonda, Martin Dreyling, Pier Luigi Zinzani, Johannes Weirather,
Maren Dirnberger-Hertweck, Sumeet Ambarkhane, Kami Maddocks
Primary Analysis Results of the Single-Arm
Phase II Study of MOR208 plus Lenalidomide
in Patients with Relapsed or Refractory
Diffuse Large B-Cell Lymphoma (L-MIND)
2
Horton et al., 2008; Awan et al., 2010; Richter et al., 2013; MorphoSys data on file; Wu et al., 2008; Lapalombella et al., 2008; Zhang et al., 2013,
Wiernik et al., 2008; Witzig et al., 2011; Czuczman et al., 2017; Jurczak et al, 2018
ADCC
ADCP
Direct Cell Death
Encouraging single agent
activity in NHL patients
with long DoR in R/R DLBCL
T and NK Cell
Activation/Expansion
Direct Cell Death
Demonstrated activity as an
anti-lymphoma agent, alone
or in combination
Approved for treatment of
MCL and FL/MZL
MOR208
Fc-enhanced, anti-CD19 mAbLenalidomide+
Potentiation of activity by combining Tafasitamab & LEN in vivo and in vitro
MOR208 (Tafasitamab) and LEN: A Novel Immunological Combination
ICML 2019 #124, Salles et al, L-MIND – June 22, 2019
3ICML 2019 #124, Salles et al, L-MIND – June 22, 2019
L-MIND: Study Designphase 2, single-arm, open-label, multicenter study (NCT02399085)
-Primary refractory DLBCL was defined as no response to or progression/relapse during or within 6 months of frontline therapy.
-Response assessment (Cheson 2007 Criteria) was after cycles 2, 4, 6, 9 and 12, thereafter every 3 cycles.
-ASCT, autologous stem cell transplant; HDCT, high-dose chemotherapy; SD, stable disease, p.o., per os.
Sample size suitable to detect ≥15% absolute increase in ORR for
Tafasitamab/LEN combination vs. LEN monotherapy at 85% power,
2-sided alpha of 5%
Mature Data: Primary Endpoint Analysis with data cut-off 30 Nov 2018; minimum
Follow-Up 12 months, median Follow-Up 17.3 months
4ICML 2019 #124, Salles et al, L-MIND – June 22, 2019
Baseline CharacteristicsCharacteristic Specification n=81 (%)
SexMale
Female44 (54)37 (46)
Age [years]* median (range) 72 (41-86)
Risk (IPI)*0-23-5
40 (49)41 (51)
Ann Arbor Stage*I-II
III-IV20 (25)61 (75)
Elevated LDH* YesNo
45 (56)36 (44)
Prior Lines*
median1234
240 (49)35 (43)5 (6)1(1)
Primary RefractoryYesNo
15 (18)66 (82)
Refractory to last prior therapy*YesNo
36 (44)45 (56)
Prior SCTYesNo
9 (11)72 (89)
Cell of Origin(Centrally assessed - Hans algorithm)
GCBNon-GCBUnknown
37 (46)20 (25)24 (30)
*at study entry
5ICML 2019 #124, Salles et al, L-MIND – June 22, 2019
Safety Profile of Tafasitamab + LEN
N=81. TEAEs, treatment-emergent adverse events, numbers represent % patients
5 infusion-related reactions in 5 patients (6%) were reported for Tafasitamab (all grade 1)
Treatment-related SAEs occurred in 15 (18.5%) patients (primarily infections [10%] or neutropenic fever [5%])
4 treatment-emergent deaths (sudden death, respiratory failure, cerebrovascular accident, PML) were reported as unrelated to study drugs
Non-hematologic TEAEs in ≥10% of patients
Hematologic TEAEs in ≥10% of patients
37 patients (43%) required LEN dose reduction
62/80 patients (78%) were able to stay at dose ≥20mg/d
6ICML 2019 #124, Salles et al, L-MIND – June 22, 2019
Tafasitamab + LEN combination (up to 12 cycles)
n = 80, median exposure 6.5 months
Tafasitamab monotherapy (cycle 13 onwards or after LEN
discontinuation) n = 37, median exposure 8.7 months
Safety by Treatment Phase
AE collection period included 30 days after end of treatment
Incidence and severity of TEAEs is lower during the Tafasitamab monotherapy phase
10 patients (12%) discontinued Tafasitamab + LEN due to AE
7ICML 2019 #124, Salles et al, L-MIND – June 22, 2019
N=80: full analysis set patients receiving at least one dose of
tafasitamab and LEN
NE due to missing post-baseline tumor assessment
Primary Endpoint: Overall Response Rate (ORR) by IRC
ORR 60.0% (95% CI 48.4% - 70.8%)
CR-rate 42.5%
• 82% of CRs PET-confirmed
• 18% of CRs based on CT only
CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease;
NE, not evaluable.
8ICML 2019 #124, Salles et al, L-MIND – June 22, 2019
Comparable ORR Observed in Most Subgroups of Interest
9ICML 2019 #124, Salles et al, L-MIND – June 22, 2019
Median DoR 21.7 mo (95% CI 21.7 – NR) Median DoR for CR patients: NR (95% CI 21.7 – NR)
Median DoR for PR patients: 4.4 mo (95%CI: 2.0 – 9.1)
Duration of Response (IRC)
10ICML 2019 #124, Salles et al, L-MIND – June 22, 2019
Progression-free Survival (IRC)
Median Follow-up Time 17.3 months
39 PFS events recorded
28 patients still ongoing with study treatmentNR = not reached
11ICML 2019 #124, Salles et al, L-MIND – June 22, 2019
Overall Survival
NR = not reached
Median Follow-up Time: 19.6 months
29 deaths recorded
12ICML 2019 #124, Salles et al, L-MIND – June 22, 2019
Conclusions
Tafasitamab + LEN showed promising activity with favourable safety profile
Consistently high activity observed in transplant ineligible patient
subgroups with limited treatment options and poor prognosis
Durable responses and favourable OS represent a remarkable outcome
Tafasitamab + LEN can be a novel, chemo-free immunotherapy for R-R
DLBCL patients
13ICML 2019 #124, Salles et al, L-MIND – June 22, 2019
Conflict of Interest Disclosure - Gilles Salles - Presentation #124
Conflicts of interest
Gilles Salles has received financial compensations for participating to advisory boards or consulting from:
Abbvie, Autolus, Celgene, Gilead, Epizyme, Janssen, Karyopharm, Kite, Merck, Morphosys, Novartis, Roche, Servier,
Takeda
For participation in educational events from:
Abbvie, Amgen, Celgene, Gilead, Janssen, Kite, Morphosys, Novartis, Roche, Servier, Takeda
We thank the patients, their families,
clinical researchers, their teams & hospitals
that are participating in the study
This study is sponsored by MorphoSys AG