Interim data from a phase 1B trial ( PN001 ) evaluating Pembrolizumab ( MK-3475 ), an investigational anti-PD-1 immunotherapy, in patients with previously-treated non-small cell lung cancer ( NSCLC ) were presented at the 15th World Conference on Lung Cancer in Sydney, Australia.

Detailed interim data were presented for response rates and safety from a cohort of 38 previously-treated NSCLC patients who received Pembrolizumab 10mg/kg every three weeks as well as initial findings from an analysis of the relationship between response rates and PD-L1 expression.

Tumor responses were assessed by investigator-assessed, immune-related response ( irRC ) criteria as well as independent, central, blinded radiographic review per Response Evaluation Criteria in Solid Tumors ( RECIST 1.1 ) criteria.

In the 38-patient cohort, the objective response rate in patients receiving Pembrolizumab was 24% based on irRC, and 21% based on RECIST ( n=33 ).
The median overall survival at time of analysis was 51 weeks with seven of the nine responders, determined by irRC, continuing on treatment.
The median response duration has not been reached at the time of this analysis.

The most commonly reported drug-related adverse events in the study ( all grades) were: rash ( 21% ), pruritus ( 18% ), fatigue ( 16% ), diarrhea ( 13% ) and arthralgia ( 11% ). The majority of adverse events were low grade ( grade 1-2 ) there was one incident of grade 3 pulmonary edema.

An analysis of the relationship between PD-L1 expression status and response rates in this NSCLC patient cohort was also presented. Tumor samples were analyzed and classified as expressing either zero/low or high levels of PD-L1.
High levels of expression according to the assay criteria, were associated with response rates of 67% ( 6/9 ) [ 95% CI; range 30, 93 ] per irRC and 57% ( 4/7 ) [ 95% CI; range 18, 90 ] per RECIST.
In comparison, tumor samples expressing zero/low levels of PD-L1, according to assay criteria, were associated with response rates of 4% ( 1/24 ) [ 95% CI; range 0, 21 ] per irRC and 9% ( 2/22 ) per RECIST [ 95% CI; range 1, 29 ].
Data from more patients are needed to better understand the relationship between PD-L1 expression and response to Pembrolizumab.

Many tumors are able to evade the immune system through a mechanism that exploits the PD-1 inhibitory checkpoint protein. Pembrolizumab is an investigational, highly selective anti-PD-1 immunotherapy designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade ( PD-L1 and PD-L2 ) of the PD-1 protein. By blocking PD-1, Pembrolizumab enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system. ( Xagena )

Source: Merck, 2013

XagenaMedicine2013