- BerGenBio's proprietary Composite AXL Tumor-Immune Score
predicts patients that have significantly prolonged clinical
benefit
- Primary endpoint of ORR in cohort A met, in predominantly
PD-L1 low/negative patients
- Combination is 5-fold more active in composite AXL positive
patients (33% ORR) vs AXL negative patients (7% ORR)
- Secondary endpoint, median Progression Free Survival of 8.4
months in composite AXL score positive patients, exceeds
expectations, 3-fold longer than for composite AXL negative
patients.
BERGEN, Norway, Nov. 8, 2019 /PRNewswire/ -- BerGenBio ASA
(OSE:BGBIO), a clinical-stage biopharmaceutical company developing
novel, selective AXL kinase inhibitors for multiple cancer
indications, today presents comprehensive clinical and
translational data from Cohort A of its Phase II clinical trial
(BGBC008) evaluating bemcentinib, its first in class selective AXL
inhibitor, in combination with MSD's, (a tradename of Merck &
Co., Inc., Kenilworth, NJ., USA)
anti-PD-1 therapy KEYTRUDA® (pembrolizumab), as a potential new
treatment regimen for previously treated advanced non-small cell
lung cancer (NSCLC) at an oral presentation at the prestigious High
Impact Clinical Trial session at the Society for Immunotherapy of
Cancer (6-10 November 2019)
conference in Washington DC.
In cohort A, 44 patients were evaluable for response; of IHC
evaluable patients: 50% were composite AXL positive, 52% were PD-L1
negative (<1%TPS), and 38% patients were PD-L1 low positive
(1-49% TPS). The primary endpoint of Overall Response Rate (ORR)
was met, with 33% ORR in AXL positive patients; five times the
response rate of AXL negative patients (7%).
A secondary endpoint of median Progression Free Survival (mPFS)
reported significant 3-fold improvement in AXL positive vs negative
patients – 8.4 months in composite AXL positive patients
significantly surpassing what has been shown historically in second
line treatment with PD-1 inhibitor monotherapy.
Dr. Matthew Krebs, MD, PhD,
the lead investigator who will give the presentation at SITC
said: "The clinical benefit seen with the drug combination in
AXL positive patients is impressive and provides a potential new
treatment approach for patients with low or negative PD-L1 status.
The mPFS observed for the AXL positive patients is far higher than
that seen with pembrolizumab monotherapy results from earlier
clinical trials for patients with PD-L1<50%. Furthermore, the
combination is well tolerated by patients."
RNA sequence analysis of pretreatment patient biopsies revealed
that clinical benefit from the combination therapy correlates
with total tumor AXL expression. A proprietary predictive signature
for response to bemcentinib and pembrolizumab combination derived
from the transcriptional analysis is enriched for genes associated
with epithelial-to-mesenchymal transition (EMT) and myeloid cell
activation. "This is exactly where we know AXL is important."
added Professor James Lorens PhD, Chief Scientific Officer of
BerGenBio.
The gene expression measured in responding patients correlates
with gene signatures known to be associated with poor prognosis and
lack of response to immunotherapy. This indicates that previously
treated patients are particularly benefiting despite exhibiting
these adverse traits. Professor Hani Gabra MD PhD, Chief Medical
Officer of BerGenBio said: "This indicates that bemcentinib is
conditioning the tumor microenvironment in AXL positive patients
and optimizing pembrolizumab response in these previously treated
patients."
Multispectral immunofluorescence analysis detected tumor
infiltrating AXL-expressing macrophages closely adjacent to T cells
in the tumors of patients who responded to the combination therapy.
"Seeing the AXL expressing macrophages interacting with T
regulatory cells in the tumor of a patient who responded to the
treatment really underscores the potential." added Dr.
Krebs.
Prof. Lorens added: "Previously we only considered
AXL expression in the tumor cells, ignoring the immune cell
compartment of the tumor. Our deeper biomarker analysis clearly
shows that our earlier tumor cell-only score did not fully capture
the population of patients who benefit from the combination." A
proprietary composite AXL tumor-immune score has now been
developed, derived from gene expression and immunohistochemistry
analysis that selects patients likely to benefit from
bemcentinib.
Richard Godfrey, Chief
Executive Officer of BerGenBio, said: "Our improved
ability to select and predict patients with durable clinical
benefit with a refined AXL composite biomarker is an important
development for our AXL targeting clinical programs. Importantly
for patients is the prolonged duration of benefit or mPFS and
improved Overall Survival (mOS), which is still maturing, these are
also critical regulatory end points. I look forward to reporting
mOS and data from additional cohorts in the coming months."
Presentation details
A phase II study of bemcentinib (BGB324), a first-in-class
selective AXL inhibitor, in combination with pembrolizumab in
patients with advanced NSCLC: Updated analysis
- Matthew G. Krebs, MD, PhD
–The University of Manchester
- Concurrent Session 206: High Impact Clinical Trials
- Oral Session
- 08 November 2019: Prince George's
Exhibition Hall C
- 5:10 – 5:25 p.m. EST (Session
runs from 4:50 – 6:15 p.m.)
Presentation will be available at www.bergenbio.com in the
section: Investors/Presentations when the presentation starts.
About AXL
AXL kinase is a cell membrane receptor and an essential mediator
of the biological mechanisms underlying life-threatening diseases.
In cancer, AXL suppresses the body's immune response to tumours and
drives cancer treatment failure across many indications. Tumour AXL
expression is associated with poor prognosis in NSCLC and most
other cancer types. AXL inhibitors, therefore, have potential high
value at the centre of cancer combination therapy, addressing
significant unmet medical needs and multiple high-value market
opportunities. Research has also shown that AXL mediates other
aggressive diseases.
About Bemcentinib
Bemcentinib (formerly known as BGB324), is a potentially
first-in-class selective AXL inhibitor in a broad phase II clinical
development programme. Ongoing clinical trials are investigating
bemcentinib in multiple solid and haematological tumours, in
combination with current and emerging therapies (including
immunotherapies, targeted therapies and chemotherapy), and as a
single agent. Bemcentinib targets and binds to the intracellular
catalytic kinase domain of AXL receptor tyrosine kinase and
inhibits its activity. Increase in AXL function has been linked to
key mechanisms of drug resistance and immune escape by tumour
cells, leading to aggressive metastatic cancers.
About BerGenBio ASA
BerGenBio is a clinical-stage biopharmaceutical company focused
on developing transformative drugs targeting AXL as a potential
cornerstone of therapy for aggressive diseases, including
immune-evasive, therapy resistant cancers. The company's
proprietary lead candidate, bemcentinib, is a potentially
first-in-class selective AXL inhibitor in a broad phase II oncology
clinical development programme focused on combination and single
agent therapy in lung cancer and leukaemia. A first-in-class
functional blocking AXL antibody (BGB149) and an AXL-ADC (ADCT-601)
are undergoing phase I clinical testing. In parallel, BerGenBio is
developing a companion diagnostic test to identify those patient
populations most likely to benefit from bemcentinib: this is
expected to facilitate more efficient registration trials
supporting a precision medicine-based commercialisation
strategy.
BerGenBio is based in Bergen,
Norway with a subsidiary in Oxford, UK. The company is listed on the Oslo
Stock Exchange (ticker: BGBIO). www.bergenbio.com
Contacts
Richard Godfrey
CEO, BerGenBio ASA
+47-917-86-304
Rune Skeie
CFO, BerGenBio ASA
rune.skeie@bergenbio.com
+47-917-86-513
International Media Relations
Mary-Jane Elliott
Chris Welsh
Nicholas Brown
Carina Jurs
Lucy Featherstone
Consilium Strategic Communications
bergenbio@consilium-comms.com
+44-20-3709-5700
Media Relations in Norway
Jan
Petter Stiff
Crux Advisers
stiff@crux.no
+47-995-13-891
Forward looking statements
This announcement may contain forward-looking statements, which
as such are not historical facts, but are based upon various
assumptions, many of which are based, in turn, upon further
assumptions. These assumptions are inherently subject to
significant known and unknown risks, uncertainties and other
important factors. Such risks, uncertainties, contingencies and
other important factors could cause actual events to differ
materially from the expectations expressed or implied in this
announcement by such forward-looking statements.
This information is subject to the disclosure requirements
pursuant to section 5-12 of the Norwegian Securities Trading
Act.
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