New clinical stage biopharmaceutical company has successfully developed a novel selective AXL kinase inhibitor to treat multiple cancers, such as lung cancer and Leukaemia.
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.
The study also focuses on the impact of the AXL kinase inhibitors on blood cancers. 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 tumour 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 tumour infiltrating AXL-expressing macrophages closely adjacent to T cells in the tumours of patients who responded to the combination therapy. “Seeing the AXL expressing macrophages interacting with T regulatory cells in the tumour 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 tumour cells, ignoring the immune cell compartment of the tumour. Our deeper biomarker analysis clearly shows that our earlier tumour cell-only score did not fully capture the population of patients who benefit from the combination.” A proprietary composite AXL tumour-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.”