Phase 1b study in patients with advanced or solid tumours
Research type
Research Study
Full title
A Phase 1b Dose Escalation Study of Cabozantinib (XL184) Administered in Combination with Atezolizumab to Subjects with Locally Advanced or Metastatic Solid Tumors
IRAS ID
228288
Contact name
Thomas Powles
Contact email
Sponsor organisation
Exelixis, Inc
Eudract number
2017-001792-24
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 9 months, 1 days
Research summary
Multi-targeted tyrosine kinase inhibitors (TKIs) and checkpoint inhibiting immunotherapies represent two types of treatment that have been important in the advancement of anti-cancer therapy. These therapies have demonstrated clinical effects across multiple tumour types including renal cell carcinoma (RCC), urothelial carcinoma (UC), melanoma, non-small-cell lung cancer (NSCLC), and others; and their success as single agents has led to interest in evaluating combinations of TKIs with checkpoint inhibitors in search of possibly cooperative, anti-cancer effects. This study would represent the first clinical evaluation of cabozantinib (a TKI) with a PD-L1 inhibitor (such as Atezolizumab).
Atezolizumab is a humanised monoclonal antibody that inhibits the interaction between a receptor present on tumour cells (PD-L1), and receptors on a types of immune cells called T cells (PD-1 and B7-1). The result is an increase in the susceptibility of tumour cells to T-cell-mediated immune response, an effect that has been demonstrated clinically, resulting in approved treatments in patients with UC and NSCLC.
Cabozantinib (XL184) is a potent inhibitor of multiple proteins called receptor tyrosine kinases (RTKs) known to play important roles in tumour cell proliferation and/or tumour neovascularisation (supply of blood vessels). It has been approved for medullary thyroid cancer (MTC) and RCC patients. Studies have shown that cabozantinib treatment affects the tumour microenvironment to make it potentially more sensitive to the antitumour effects of the immune system.
This study consists of two stages: Dose Escalation and Dose Expansion. Only the Dose Expansion Stage will be run in the UK. In the Dose Expansion Stage, up to 120 participants, in four tumour-specific cohorts (UC and RCC) will receive the combination treatment to further evaluate the safety and preliminary anticancer activity of the combination therapy.
REC name
London - Westminster Research Ethics Committee
REC reference
17/LO/1629
Date of REC Opinion
3 Nov 2017
REC opinion
Further Information Favourable Opinion