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
Author(s): ,
Max Topp
Affiliations:
University Hospital Würzburg,Würzburg,Germany
,
Johannes Duell
Affiliations:
University Hospital Würzburg,Würzburg,Germany
,
Gerhard Zugmaier
Affiliations:
Amgen Research (Munich),Munich,Germany
,
Michel Attal
Affiliations:
University of Toulouse,Toulouse,France
,
Philippe Moreau
Affiliations:
University Hospital Center of Nantes,Nantes,France
,
Christian Langer
Affiliations:
Kempten Clinic,Kempten,Germany
,
Jan Kroenke
Affiliations:
Ulm University,Ulm,Germany
,
Thierry Facon
Affiliations:
Regional University Hospital of Lille,Lille,France
,
Alexey Salnikov
Affiliations:
Boehringer Ingelheim,Biberach,Germany
,
Robin Lesley
Affiliations:
Amgen Inc.,South San Francisco,United States
,
Karl Beutner
Affiliations:
Amgen Inc.,Thousand Oaks,United States
,
James Kalabus
Affiliations:
Amgen Inc.,South San Francisco,United States
,
Erik Rasmussen
Affiliations:
Amgen Inc.,Thousand Oaks,United States
,
Kathrin Riemann
Affiliations:
Boehringer Ingelheim,Biberach,Germany
,
Alex Minella
Affiliations:
Amgen Inc.,Thousand Oaks,United States
,
Gerd Munzert
Affiliations:
Boehringer Ingelheim,Biberach,Germany
Hermann Einsele
Affiliations:
University Hospital Würzburg,Würzburg,Germany
EHA Library. Topp M. Jun 15, 2019; 267408; S825
Dr. Max Topp
Dr. Max Topp
Contributions
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Abstract

Abstract: S825

Type: Oral Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 12:00 - 12:15

Location: Auditorium

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

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. 

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.  

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. 

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.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Dose escalation, Immunotherapy, Minimal residual disease (MRD), Multiple myeloma

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