BerGenBio Meets First Efficacy Endpoint in Phase II Trial With Selective AXL Inhibitor BGB324 (bemcentinib) in NSCLC

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

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