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Shaun Villa



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    P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.06-09 - MiST3: A Phase II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with Pembrolizumab in pts with Malignant Mesothelioma (ID 12548)

      16:45 - 18:00  |  Author(s): Shaun Villa

      • Abstract

      Background

      Mesothelioma is a cancer with significant unmet need, with only one line of therapy licenced in the UK. AXL is a member of the TAM (Tyro3, AXL, Mer) family of receptor tyrosine kinases that regulate multiple cellular processes including survival, proliferation and migration. An analysis of AXL expression in patients with mesothelioma reported an overexpression in 74% of the tumours examined. Several cell types associated with the suppressive tumour immune microenvironment express AXL, including natural killer cells and tumour-associated macrophages. AXL is an important regulator of tumour plasticity related to epithelial-to-mesenchymal transition, thereby contributing to evasion of antitumour immune response. Hence, AXL signalling contributes uniquely to tumour intrinsic and microenvironmental immune suppression. Bemcentinib (BGB324), a potent, selective orally bioavailable small molecule inhibitor of AXL, has demonstrated effective inhibition in pre-clinical models and is currently being trialled in combination with pembrolizumab in patients with advanced non-small-cell lung cancer, breast cancer and melanoma.

      Pembrolizumab has high affinity and potent receptor blocking activity for PD-1, therefore inhibiting the interaction with PD-L1. Recent data showed that the combination of bemcentinib with anti-PD-1 blockade profoundly enhanced anti-tumour activity in the syngeneic Lewis Lung (LL/2) lung carcinoma model.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a single arm phase IIA clinical trial of bemcentinib and pembrolizumab in patients with relapsed mesothelioma. MiST3 is one arm of a broader umbrella study- a stratified multi-arm phase IIA clinical trial to enable accelerated evaluation of targeted therapies for relapsed malignant mesothelioma. 25 patients recruited to MiST3 will receive a loading dose of 400mg bemcentinib, followed by daily doses of 200mg, alongside IV infusions of 200mg pembrolizumab on day-one of each 21-day cycle. The primary objective is to establish 12 week disease control rate (DCR), secondary objectives include safety and tolerability, objective response rate and 24 week DCR, as assessed by modified RECIST. Patients will continue therapy until disease progression, unacceptable toxicity or a maximum 2-year duration. A pre-treatment biopsy and serial plasma samples will be mandatory for exploratory research.

      Exploratory objectives include; correlation of PD-L1 and AXL expression levels with response to treatment, tumour mutation burden to interrogate the genomic correlates of treatment response, immune regulated gene signature in RNA extracted from tumour samples, to correlate the impact of tumour infiltrating lymphocytes with response, and correlations between gut microbiome composition and response to therapy will be sought using 16sRNA sequencing. First patient first visit is anticipated- Q3 2018.

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion

      Section not applicable

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