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EVALUATION OF AMG 420, AN ANTI-BCMA BISPECIFIC T-CELL ENGAGER (BITE®) IMMUNOTHERAPY, IN R/R MULTIPLE MYELOMA (MM) PATIENTS: UPDATED RESULTS OF A FIRST-IN-HUMAN (FIH) PHASE 1 DOSE ESCALATION STUDY

S825

Topp, M.1; Duell, J.1; Zugmaier, G.2; Attal, M.3; Moreau, P.4; Langer, C.5; Kroenke, J.6; Facon, T.7; Salnikov, A.8; Lesley, R.9; Beutner, K.10; Kalabus, J.9; Rasmussen, E.10; Riemann, K.8; Minella, A.10; Munzert, G.8; Einsele, H.1

doi: 10.1097/01.HS9.0000561580.66319.3d
Simultaneous Sessions II: Immunotherapy in relapsed/refractory multiple myeloma
Free

1University Hospital Würzburg, Würzburg

2Amgen Research (Munich), Munich, Germany

3University of Toulouse, Toulouse

4University Hospital Center of Nantes, Nantes, France

5Kempten Clinic, Kempten

6Ulm University, Ulm, Germany

7Regional University Hospital of Lille, Lille, France

8Boehringer Ingelheim, Biberach, Germany

9Amgen Inc., South San Francisco

10Amgen Inc., Thousand Oaks, United States

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Background:

BCMA, a member of the TNFR family, is expressed on MM and plasma cells (PC).

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Aims:

Objectives of this study included assessing safety and activity of AMG 420/BI 836909, which binds BCMA (B-Cell Maturation Antigen) on MM cells and CD3 on T cells, in relapsed and/or refractory (R/R) MM.

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Methods:

In this FIH study (NCT02514239), 6-week cycles of AMG 420 were given for ≤5 cycles or until disease progression (PD), toxicity, or consent withdrawal; 5 more cycles could be given for benefit. Eligible patients had progression after ≥2 lines (incl PI and IMiD). Excluded were PC leukemia, extramedullary relapse, CNS involvement, or prior allo-SCT. MRD was defined as <1 tumor cell / 104 bone marrow cells per flow cytometry.

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Results:

As of Dec 10, 2018, 42 patients received AMG 420 (0.2-800 μg/d). Patients D/C for PD (n = 24), adverse events (AE, n = 7, incl 3 DLTs), death (4), completed 10 cycles (2), and consent (1). Median age was 65 y, median MM duration 5.2 y, and median # prior therapies 4. Patients were treated for a mean (SD) of 2.5 (2.6) cycles.

There were 2 deaths from AEs (acute respiratory distress from flu / aspergillosis; fulminant hepatitis related to adenovirus infection); neither treatment related. Of those with serious AEs (SAEs, n = 21, 50%), 18 required hospitalization. SAEs occurring in >1 patient were infections (n = 12) and polyneuropathy (PN, n = 2). Treatment-related SAEs included 2 grade 3 PNs and 1 edema. Grade 2-3 CRS was seen in 3 patients. No anti-AMG 420 Ab were detected. In this study, 800 μg/d was determined to not be tolerable as 2/3 patients had DLTs, 1 case of grade 3 CRS and 1 case of grade 3 PN; both required hospitalization and subsequently resolved.

At 400 μg/d, there were 5 minimal residual disease (MRD)-negative sCRs, 1 VGPR, and 1 PR, for a response rate of 7/10 (70%); at Dec datacut, responses lasted for 5.6-10.4 months with 4 patients ongoing on treatment. As of Feb 2019, some responses lasted >1 year. Overall, there were 13/42 responders (6 sCRs, 3 CRs, 2 VGPRs, 2 PRs). Median time to any response was 1 month, with 9 of 13 patients responding in the first cycle.

Figure

Figure

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Summary/Conclusion:

In this FIH study of AMG 420, a BiTE® vs BCMA, in R/R MM, there was a 70% response rate (7/10) with 5 out of 7 responders achieving a sCR at 400 μg/d, a recommended dose for further investigation.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.