THE COMBINATION OF BEMCENTINIB, A NOVEL, ORAL, SELECTIVE AXL-INHIBITOR AND LOW-DOSE CYTARABINE YIELDS DURABLE RESPONSES IN AML PATIENTS UNFIT FOR INTENSIVE CHEMOTHERAPY
Author(s): ,
Sonja Loges
Affiliations:
Department of Oncology, Hematology, BMT with Section Pneumology and Institute of Tumor Biology,University Medical Center Hamburg-Eppendorf,Hamburg,Germany
,
Michael Heuser
Affiliations:
Hannover Medical School,Hannover,Germany
,
Jörg Chromik
Affiliations:
University Hospital Frankfurt,Frankfurt,Germany
,
Carlos Enrique Vigil
Affiliations:
Vanderbilt-Ingram Cancer Center,Nashville,United States
,
Peter Paschka
Affiliations:
University Hospital of Ulm,Ulm,Germany
,
Francesca Re
Affiliations:
University of Parma,Parma,Italy
,
Nicola Di Renzo
Affiliations:
Haematology and SCT Unit,Vito Fazzi Hospital,Lecce,Italy
,
Roberto Lemoli
Affiliations:
University of Genoa,Genoa,Italy
,
Daniele Mattei
Affiliations:
ASO S. Croce e Carle,Cuneo,Italy
,
Isabel Ben Batalla
Affiliations:
Medical Clinic and Institute of Tumor Biology, Campus Forschung,University Hospital Hamburg-Eppendorf,Hamburg,Italy
,
Monica Hellesøy
Affiliations:
Haukelands University Hospital,Bergen,Norway
,
David Micklem
Affiliations:
BerGenBio ASA,Bergen,Norway
,
Robert J Holt
Affiliations:
BerGenBio ASA,Bergen,Norway
,
Julia Schoelermann
Affiliations:
BerGenBio ASA,Bergen,Norway
,
Katherine Lorens
Affiliations:
BerGenBio ASA,Bergen,Norway
,
James B. Lorens
Affiliations:
Centre for Cancer Biomarkers,University of Bergen,Bergen,Norway
,
Muhammad Shoaib
Affiliations:
BerGenBio ASA,Bergen,Norway
,
Hassan Aly
Affiliations:
BerGenBio ASA,Bergen,Norway
,
Anthony Brown
Affiliations:
BerGenBio ASA,Bergen,Norway
,
Walter M. Fiedler
Affiliations:
Hubertus-Wald University Cancer Center,University Medical Center Hamburg-Eppendorf,Hamburg,Germany
,
Jorge E. Cortes
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
Bjørn T. Gjertsen
Affiliations:
Centre for Cancer Biomarkers CCBIO, Department of Clinical Science,University of Bergen,Bergen,Norway
EHA Library. Loges S. Jun 14, 2019; 266059; PF259
Sonja Loges
Sonja Loges
Contributions
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Abstract

Abstract: PF259

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background
There is an unmet need in treating AML pts who are unable to tolerate high-intensity chemo. Treatment of AML pts ≥75 yo is particularly challenging due to co-morbidities, low treatment tolerance and poor risk disease features in at least half of these pts. Low-dose cytarabine (LDAC) monotherapy is an approved therapy for elderly pts unfit for intensive chemo and yields 18% CR rate as reported in the MRC AML14 study with median OS of 3-4 months. In order to improve the OS of this challenging pt population, an increase in the CR rate and longer response duration is required. The RTK AXL represents a novel therapeutic target promoting AML cell proliferation and survival by pleiotropic mechanisms and is a negative regulator of anti-tumor immunity. Bemcentinib is a first-in-class, highly selective, oral AXL inhibitor that has previously shown a 43% ORR among 14 r/r AML/hr-MDS pts with low sAXL, with a favorable safety profile. T- and B-cell receptor diversification as well as clonal stabilization were also reported.

Aims
The open label study BGBC003 aimed to establish the RP2D and anti-leukemic activity of bemcentinib when given as a monotherapy followed by a PhII part designed to explore the safety and efficacy of bemcentinib given in combo with LDAC to patients with newly diagnosed or R/R AML unfit for intensive chemotherapy. Secondary objectives included OS and exploratory biomarker analyses.

Methods
The monotherapy dose-escalation part of the study is complete. During the PhII part, AML pts unfit for intensive therapy received bemcentinib at RP2D (200mg PO/d) + SOC 10-day LDAC in 21-day cycles. At the time of writing, 10 pts were evaluable for response assessment by BM aspirate at C2D1: median age was 76y (range 66-83); 6 patients (60%) had poor cytogenetic risk profile, 1 (10%) and 3 (30%) had favorable or unknown risk, respectively; pts showed a median of 33% myeloblasts at screen (range 3-96%) and 9 of 9 patients (100%) tested for FLT mutations were negative. 6/10 pts (60%) were previously treated including 3 relapsed and 3 refractory. Plasma protein biomarker levels including soluble AXL (sAXL) were measured using the DiscoveryMap v3.3 panel (Myriad RBM) at screen and following treatment.

Results
As of March 2019, 4/10 evaluable patients had objective responses (40%, 3 CR/CRi+1 PR), all starting at C2D1. Responses occurred in pts with unfavorable characteristics: 2 previously-treated including 1 refractory, 3 unfavorable cytogenetics, and 3 >75 yo. CRs were durable at 3.5, 4.9 and 6.9 mos (all ongoing). The pt with PR continues treatment in cycle 2 at time of writing. 2 additional pts (20%, both 76y, 1 relapsed and 1 secondary) showed a durable stable disease at 4.0 and 3.9 mos (1 ongoing). The combo was well tolerated with expected and manageable AEs. Out of all pts dosed with bemcentinib + LDAC, 4 experienced TRAEs (4/13, 31%). The most common TRAEs in this group were anemia (2/13, 15%) and diarrhea (2/13, 15%). 2 pts experienced TRAEs grades 3+ (anemia, thrombocytopenia/PLT count decreased). 2 pts reported febrile neutropenia, none of which were related to the study drug. No tumor lysis syndrome events have been reported.

Conclusion
The potential new non-intensive combo regimen, bemcentinib + LDAC, induced a response rate of 40% with durable CR/CRis lasting up to 7 mos at time of writing. Responses were seen in elderly AML patients including previously-treated patients and those with poor-risk disease, and the combo has the potential to increase the median OS among both relapsed as well as De Novo AML pts not eligible for intensive chemotherapy.

Session topic: 4. Acute myeloid leukemia - Clinical

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