Checkmate Pharmaceuticals has commenced a Phase 1b trial of CMP‐001 in combination with atezolizumab (TECENTRIQ) for the treatment of patients with advanced non‐small cell lung cancer (NSCLC) and disease progression before anti‐PD‐1/PD‐L1 therapy.
As part of the multi‐centre, open label, two‐part trial, the combination of CMP‐001 and atezolizumab will be given to patients with and without low‐level radiation therapy.
In the first part of the trial, Checkmate will analyse 5mg weekly dose of CMP‐001 for two weeks and then intratumorally (IT) weekly for three weeks, followed by either SC or IT injection every three weeks.
In the second part, the combination of CMP‐001 and atezolizumab will be administered before low‐level radiation therapy to the target lesion.
Patients will be observed for safety and tolerability, as well as clinical response during the trial.
Checkmate also plans to conduct correlative studies to characterise the immune effects of the treatment in the blood and tumours.
Checkmate Pharmaceuticals founder and CEO Art Krieg said: “The mechanism of action of CMP 001 should apply across most or all tumour types, and so we expect CMP-001 to reverse PD‐1 resistance in NSCLC, just as we reported for PD‐1 resistant advanced melanoma last week at the 2018 American Association of Cancer Research Annual Meeting in Chicago.
“In our ongoing melanoma trial we learned that patients whose tumours contain more plasmacytoid dendritic cells (pDC) appear to be more likely to respond to CMP‐001 in combination with checkpoint inhibitor therapy.
“Low dose radiation therapy recruits pDC into tumours, and so we expect this triple combination regimen to increase the response rate to our therapy.”
CMP‐001 is a CpG‐A Toll‐like receptor 9 (TLR9) agonist, and is developed to activate innate immunity to convert ‘uninflamed’ tumours that usually do not respond to anti-PD-1/L1 therapy, into ‘inflamed’ tumours, which are responsive to PD‐1 inhibition.