A lung-cancer vaccine trial drew T cells and no responses
A phase I trial injected dendritic cells carrying the CCL21 gene into advanced non-small cell lung tumours, together with pembrolizumab. Eleven patients were in dose escalation. A further cohort of 12 was treated at the expansion dose, 30 million cells whenever the vaccine was injected. No objective response occurred. Stable disease was the best result for 36.8 percent. The response-rate endpoint was missed. Later biopsies found new T-cell clones, and many of those clones did not last.
Science··Midday
The highest dose was 30 million cells a shot
Immune checkpoint drugs have changed care for non-small cell lung cancer, and resistance to them is common. This phase I trial added an intratumoral injection of dendritic cells modified to express CCL21, given with pembrolizumab, in people with advanced disease. The registry identifier is NCT03546361. Primary aims were the maximum administered dose during escalation, and the objective response rate during expansion.[1]
Eleven patients entered the escalation group. In the expansion group, 12 patients received the maximum administered dose, 30 million cells at each injection. The combination was described as well tolerated.[1]
Stable disease in 36.8 percent, and no responses
No objective responses were observed, so the trial missed its primary endpoint on response rate. The best response was stable disease in 36.8 percent of patients. A phase I series of this size can set a dose and describe tolerability; it cannot establish that a treatment lengthens life.[1]
New T cells arrived and many did not stay
Later biopsies, read after the trial’s main clinical question, showed more CD4-positive T cells in the tumour and new T-cell clones. Stable disease went together with a broader T-cell receptor repertoire and with greater expansion of those new clones.[1]
Many of the new clones failed to persist. Signatures of myeloid cells linked to immune suppression were present at the sampled times. The authors’ reading is that CCL21 dendritic cells plus pembrolizumab can bring T cells in, and that this did not become meaningful clinical efficacy. They point to T cells that recognised the tumour only weakly, and to surrounding tissue that kept its old suppressive pattern.[1]
