engineering the medicines of tomorrow...icml 2019 #124, salles et al, l-mind –june 22, 2019 5...

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


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


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


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


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.


Comparable ORR Observed in Most Subgroups of Interest


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)


Progression-free Survival (IRC)

Median Follow-up Time 17.3 months

39 PFS events recorded

28 patients still ongoing with study treatmentNR = not reached


Overall Survival

NR = not reached

Median Follow-up Time: 19.6 months

29 deaths recorded


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


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

engineering the medicines of tomorrow...icml 2019 #124, salles et al, l-mind –june 22, 2019 5...

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