Among patients with non-small cell lung cancer (NSCLC) treated with the investigational immune checkpoint inhibitor MK-3475, those whose tumours had high levels of the protein PD-L1 had significantly better outcomes, according to results of a phase I clinical trial presented at the AACR Annual Meeting.

Preliminary data from the trial, which were reported earlier this year, showed that MK-3475 treatment was well tolerated and led to durable, objective responses in previously treated patients with NSCLC, particularly those with tumours found to have high levels of PD-L1 prior to treatment.

The latest results extend these data, showing that at six months after starting treatment, 41 percent of patients whose tumours had high levels of PD-L1 had no disease progression, compared with 17 percent of those whose tumours had low levels of PD-L1.

Similarly, 72 percent of patients whose tumours had high levels of PD-L1 were alive at this time, compared with 53 percent of those whose tumours had low levels of PD-L1.

“Patients with previously treated NSCLC have a very poor outlook and there is a real need for new treatment options,” said Leena Gandhi, M.D., Ph.D., assistant professor of medicine at Harvard Medical School in Boston.

“The responses we have seen among patients whose tumours express high levels of PD-L1 appear to be quite durable, which is extremely exciting.

“Immune cells called T cells are naturally capable of destroying cancer cells,” explained Gandhi, who is also a thoracic oncologist at the Dana-Farber Cancer Institute.

“But some cancer cells are able to prevent T cells from attacking them by activating the T cells’ ‘brakes.’

One way they do this is via a protein called PD-L1 on their surface, which attaches to a protein on the surface of T cells, PD-1.

MK-3475 disables this brake by blocking PD-1 on the T cells and preventing it from attaching to PD-L1.”

Gandhi and colleagues enrolled patients with NSCLC to multiple cohorts on the phase I clinical trial.

When they analysed the data based on pretreatment tumour PD-L1 levels, information they were able to obtain for 146 patients, it was found that levels of PD-L1 of greater than 50 percent, as measured by immunohistochemistry, served as the best cutoff point for differentiating outcomes for PD-L1-positive versus PD-L1-negative tumours.

For the group of 41 patients with high pretreatment tumour PD-L1 levels, response rate was 37 percent as compared with 11 percent for those with low pretreatment tumour PD-L1 levels.

“These data strongly suggest that high levels of tumour PD-L1 may be a good biomarker for determining which patients with NSCLC are most likely to benefit from treatment with MK- 3475,” said Gandhi.

“We will present outcome data on this full group of patients who have now had PD-L1 expression analysed.

These results extend our findings from the initial 38 patients, and an ongoing, randomised study will prospectively evaluate the role of PD-L1 expression in determining outcome to MK3475 versus docetaxel therapy.”

Source: AACR