ASpiRE
Research type
Research Study
Full title
ASpiRE: A proof-of-mechanism and proof-of-concept clinical trial evaluating the safety, tolerability, biological and anti-tumour activity of Apalutamide with dual CXCR1 and CXCR2 blockade by SX-682 for men suffering from metastatic castration-resistant prostate cancer (mCRPC)
IRAS ID
1008729
Contact name
Johann De Bono
Contact email
Sponsor organisation
The Institute of Cancer Research
Research summary
ASpiRE will investigate the effect of the drug SX-682 in combination with Apalutamide in men suffering from metastatic castration-resistant prostate cancer (mCRPC). SX-682 blocks two key molecules (CXCR1 and CXCR2) involved in the inflammation pathway, which can cause resistance to endocrine therapy for this disease.
ASpiRE will succeed ACE, which investigated the combination of the CXCR2 inhibitor AZD5069 with enzalutamide in mCRPC. CXCR2 is a receptor to chemokines, which are small chemical messengers released by cells that influence the behaviour of immune cells. In prostate cancer, CXCR2 signalling leads to the migration of a set of immune cells called myeloid cells, which work together with cancer cells and lead to cancer progression and resistance to therapy. In ACE, it was demonstrated that blocking CXCR2 with AZD5069 reduced myeloid cells in tumours and improved the efficacy of enzalutamide. However, in this study, it was also found that blocking CXCR2 increased other chemokine molecules such as CXCL1, CXCL2 and CXCL8, which can signal through another chemokine receptor known as CXCR1. This suggests that the activity of CXCR1 may limit the efficacy of blocking only CXCR2. As such, combined CXCR1 and CXCR2 inhibition may be required to maximally block myeloid cells from infiltrating prostate tumours and make endocrine therapy more effective.
As such, we plan to investigate the dual CXCR1 and CXCR2 inhibitor SX-682 in combination with Apalutamide. This is to study effect of SX-682 in reversing resistance to endocrine therapy.
This is a phase 1/2 study. In phase 1, we will investigate escalating doses of SX-682 in combination with a fixed dose of Apalutamide to identify a biologically active and tolerable dose range. In phase 2, we will further assess the safety of at least two dose levels to estimate the anti-tumour activity of SX-682 when administered with Apalutamide to determine the best dose.
REC name
London - City & East Research Ethics Committee
REC reference
25/LO/0082
Date of REC Opinion
11 Mar 2025
REC opinion
Further Information Favourable Opinion