FAK-PD1 v1

  • Research type

    Research Study

  • Full title

    A Phase I/IIA Study to Assess Safety, Tolerability and Preliminary Activity of the Combination of FAK (Defactinib) and PD-1 (Pembrolizumab) Inhibition in Patients with Advanced Solid Malignancies

  • IRAS ID

    200488

  • Contact name

    Stefan Symeonides

  • Contact email

    stefan.symeonides@ed.ac.uk

  • Sponsor organisation

    NHS Greater Glasgow and Clyde

  • Eudract number

    2015-003928-31

  • Duration of Study in the UK

    4 years, 0 months, 0 days

  • Research summary

    ’Background\nThere is a well-justified interest about cancer immunotherapy. Drugs blocking a molecule called ’Programmed cell death receptor 1(PD-1)’ can release the body’s own immune response to attack tumour cells and clinical trials have\n \nshown that this can shrink tumours in 20-50% of patients with cancers such as melanoma, bladder, renal & non-small cell lung cancer (NSCLC). Treatment has been well-tolerated and patients can have a durable benefit. Unfortunately, other tumour-types (such as pancreatic) have been poorly responsive and it is likely that the activity is limited by the presence of other cells which are continuing to suppress the immune response. We have recently shown that a molecule called ’Focal Adhesion Kinase (FAK)’, which is involved in how a cell interacts with its local environment, has a key role in how various cancer-associated cells interact with immune cells. Blocking FAK has the potential to re-model that environment, shifting the balance from inhibitory cells to ones which support an anticancer immune response and anti-PD-1immunotherapy.\n\nAims:\nThis study will explore whether defactinib (VS-6063) (a FAK inhibitor) can be safely & tolerably combined with pembrolizumab (a PD-1) inhibitor), and will look for early indications of improved anticancer immunotherapy. It will focus on three key cancers, all in clear need of improved therapies. NSCLC, aiming to augment the moderate activity of PD-1 inhibition alone. Pancreatic cancer, aiming to release immunological activity in this otherwise resistant cancer. Finally, mesothelioma, where emerging data suggests both agents may have individual activity.\n\nMethods\nThis is a phase lb/lla trial in 50-60 patients with advanced cancer, looking at the safety & tolerability of increasing doses of defactinib (VS-6063) and pembrolizumab and then testing their activity in NSCLC, pancreatic cancer and mesothelioma. Clinical activity will be explored, as well as laboratory work to characterise the biological effects.’

  • REC name

    West of Scotland REC 1

  • REC reference

    16/WS/0093

  • Date of REC Opinion

    20 Jul 2016

  • REC opinion

    Further Information Favourable Opinion