BERGEN, Norway, Jan. 9, 2018 /PRNewswire/ --
BerGenBio ASA (OSE:BGBIO), a clinical-stage biopharmaceutical
company developing novel, selective Axl kinase inhibitors as a
potential cornerstone of combination cancer therapy, announces that
the first efficacy endpoint has been met in its phase II clinical
trial evaluating BGB324 (bemcentinib), a selective AXL inhibitor,
in combination with erlotinib in patients with advanced non-small
cell lung cancer (NSCLC) who have progressed on an approved EGFR
inhibitor (ClinicalTrials.gov Identifier: NCT02424617).
The trial (known as BGBC004) is designed to test the hypothesis
that selective AXL inhibition with the once-daily oral small
molecule bemcentinib may reverse and prevent resistance to
erlotinib, a therapy targeting constitutively active epidermal
growth factor receptor (EGFR) signalling - a pathway frequently
upregulated in cancers, particularly NSCLC. The trial is enrolling
patients with activating EGFR mutations across three
settings:
- Arm A is designed to determine the daily dose of
bemcentinib that can be safely administered in combination with
erlotinib in patients who have received prior erlotinib therapy.
This arm is completed and a recommended phase II dose has been
established.
- Arm B follows a Simon-like two-stage design evaluating
the ability of bemcentinib to restore sensitivity to EGFR targeted
therapy when given in combination with erlotinib in patients who
have progressed on prior therapy with an approved EGFR inhibitor
and that are negative for the T790M mutation. This arm has
successfully completed its first stage (announced today). The
initial endpoints of the first stage of Arm B were exceeded. An
overall disease control rate of 33% was reported in patients who
completed at least one cycle of treatment (n=9) thus providing
preliminary proof of concept that bemcentinib can restore
sensitivity to EGFR targeted therapy in some patients.
- Arm C is designed to evaluate the ability of bemcentinib
to prevent acquired resistance to EGFR targeted therapy when given
in combination with erlotinib first line. This arm is recruiting
patients with interim results expected mid-2018.
The Company expects to present clinical data from this study at
an international cancer conference during 2018.
Richard Godfrey, Chief
Executive Officer of BerGenBio, commented: "Meeting this
initial clinical endpoint in this very challenging patient
population, who have already progressed on prior EGFR targeted
therapy and who do not have a T790M resistance mutation, is an
important proof of concept for our hypothesis that bemcentinib, our
selective oral AXL inhibitor, may be effective in restoring
sensitivity to targeted therapy. Two patients in Arm B continue on
study and are experiencing sustained disease control and one
patient in Arm A is approaching their two-year anniversary on
bemcentinib in combination with erlotinib and is asymptomatic. The
BGBC004 trial forms an integral part of our strategy to evaluate
bemcentinib as a cornerstone of cancer therapy with targeted-,
immune- and chemotherapy. Bemcentinib is currently being evaluated
in two other clinical trials in NSCLC, in combination with immune-
and chemotherapy; the initial positive chemo combination data were
reported in December 2017. Further
phase II combination trials with bemcentinib are ongoing in breast
cancer, melanoma and acute myeloid leukaemia and we look forward to
reporting progress across our broad phase II clinical trial
programme at upcoming medical congresses."
About EGFR mutation driven NSCLC and targeted EGFR inhibitors
Lung cancer is the leading cause of cancer death among both men
and women and it is estimated that around 200,000 new cases of
non-small cell lung cancer (NSCLC) will be diagnosed in the US in
2018[1]. 15-20%[2] of NSCLC cases are EGFR mutant (EGFRm) leading
to constitutively active epidermal growth factor receptor (EGFR)
signalling driving the growth of tumour cells. This signalling
pathway can be effectively blocked using targeted EGFR tyrosine
kinase inhibitors (EGFR TKIs). However, virtually all patients
ultimately acquire resistance to EGFR TKIs leading to disease
progression: the median progression free survival of patients
receiving first line EGFR inhibitors erlotinib or gefitinib is 10.2
months[3]. Resistance is driven by either the acquisition of
additional mutations (e.g. the EGFR T790M mutation) or – in up to
half of the patients – bypass mechanisms[4],[5],[6]. While third
generation EGFR inhibitors targeting the T790M mutation have shown
good results, novel treatments overcoming resistance in T790M
negative patients are urgently needed. Additionally, strategies to
prevent or delay resistance in NSCLC EGFRm patients receiving first
line EGFR inhibitors are a major unmet need.
About the BGBC004 trial
The BGBC004 trial is a phase I/II multi-centre open-label study
of BGB324 in combination with erlotinib in patients with
EGFR mutation driven Stage IIIb or Stage IV NSCLC. The trial is
designed to evaluate reversal of resistance to EGFR targeted
therapy in later line patients who are negative for the T790M
mutation as well as prevention of resistance in patients receiving
the EGFR inhibitor erlotinib first line. Patients are currently
being enrolled at centres across in the US. For more information
please access trial NCT02424617 at
www.clinicaltrials.gov.
About BerGenBio ASA
BerGenBio ASA is a clinical-stage biopharmaceutical company
focused on developing a pipeline of first-in-class Axl kinase
inhibitors as a potential cornerstone of combination cancer
therapy. The Company is a world leader in understanding the
essential role of Axl kinase in mediating cancer spread, immune
evasion and drug resistance in multiple aggressive haematological
and solid cancers.
BerGenBio's lead product, BGB324 (bemcentinib), is a unique and
highly selective, potent and orally bio-available small molecule
Axl inhibitor, currently in four Company sponsored phase II
clinical trials in major cancer indications, with read-outs
anticipated in the second half of 2018. It is the only selective
oral Axl inhibitor in clinical development.
The Company sponsored clinical trials are:
- BGB324 as a single agent and combination therapy in acute
myeloid leukaemia (AML) / myeloid dysplastic syndrome (MDS)
- BGB324 with TARCEVA® (erlotinib) in advanced EGFR mutation
driven non-small cell lung cancer (NSCLC)
- BGB324 with KEYTRUDA® (pembrolizumab) in advanced
adenocarcinoma of the lung, and
- BGB324 with KEYTRUDA in triple negative breast cancer
(TNBC).
The clinical trials combining BGB324 with KEYTRUDA in
adenocarcinoma of the lung and TNBC are conducted in collaboration
with Merck & Co. Inc. (MSD), through a subsidiary.
In addition, a number of investigator-sponsored trials are
underway, including a trial to investigate BGB324 with either
MEKINIST® (trametinib) plus TAFINLAR® (dabrafenib) or KEYTRUDA in
advanced melanoma, as well as a trial combining BGB324 with
docetaxel in advanced NSCLC.
BerGenBio is simultaneously developing a companion diagnostic
test to identify patient subpopulations most likely to benefit from
treatment with BGB324. This will facilitate more efficient
registration trials and support a precision medicine based
commercialisation strategy.
The Company is also developing a diversified pre-clinical
pipeline of drug candidates, including BGB149, an anti-AXL
monoclonal antibody.
For further information, please visit: www.bergenbio.com
KEYTRUDA® is a registered trademark of Merck Sharp &
Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, TARCEVA® is a registered
trademark of OSI Pharmaceuticals, LLC., marketed by
Roche-Genentech. TAFLINAR® is a registered trademark of Novartis
International AG and MEKINIST® is a registered trademark of GSK
plc.
This information is subject to the disclosure requirements
pursuant to section 5-12 of the Norwegian Securities Trading
Act.
References
[1] American Cancer Society – Lung Cancer Statistics –
https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/key-statistics.html, accessed
January 2018
[2] Siegelin M et al. Epidermal growth factor receptor
mutations in lung adenocarcinoma. Nature (2013)
[3] Ramalingam S, et al. Osimertinib vs SoC EGFR-TKI as
First-Line Treatment in Patients with EGFRm Advanced NSCLC
(FLAURA). Presented at the European Society for Medical Oncology
(ESMO) 2017 Congress, 8-12 September
2017, Madrid,
Spain.
[4] Yu HA, et al. Analysis of Tumour Specimens at the
Time of Acquired Resistance to EGFR-TKI Therapy in 155 Patients
with EGFR-Mutant Lung Cancer. Clin Cancer Research.
(2013)
[5] Chong CR et al. The quest to overcome resistance to
EGFR-targeted therapies in cancer. Nature (2013)
[6] Husain H et al. Strategies to Overcome Bypass
Mechanisms Mediating Clinical Resistance to EGFR Tyrosine Kinase
Inhibition in Lung Cancer. Molecular Cancer Therapeutics (2017)
Contacts:
Richard Godfrey
CEO, BerGenBio ASA
+47-917-86-304
Tom Henrik Sundby
Finance Director, BerGenBio ASA
+47-477-54-415
tom.sundby@bergenbio.com
Media Relations
David
Dible, Mark Swallow,
Marine Perrier
Citigate Dewe Rogerson
bergenbio@citigatedewerogerson.com
+44-207-638-9571
This information was brought to you by Cision
http://news.cision.com
http://news.cision.com/bergenbio-asa/r/bergenbio-meets-first-efficacy-endpoint-in-phase-ii-trial-with-selective-axl-inhibitor-bgb324--bemce,c2427359
The following files are available for download:
http://mb.cision.com/Main/15728/2427359/775107.pdf
|
PDF
|
http://news.cision.com/bergenbio-asa/i/bgb324,c2317398
|
BGB324
|