Positive results from two phase II studies that evaluated the investigational cancer immunotherapy Atezolizumab ( anti-PDL1; MPDL3280A ) in people with advanced non-small cell lung cancer ( NSCLC ) were presented at European Cancer Congress.
In the randomised phase II study, POPLAR, Atezolizumab met its primary endpoint and showed a statistically significant survival benefit compared to chemotherapy ( hazard ratio, HR=0.54; p=0.014 ) in people with recurrent NSCLC whose tumours expressed medium and high levels of PD-L1, which corresponded with people living 7.7 months longer than people who received Docetaxel ( Taxotere ) chemotherapy.
A separate, single-arm phase II study, BIRCH, met its primary endpoint and showed that Atezolizumab shrank tumours ( objective response rate, ORR ) in up to 27% ( p=0.0001 ) of people whose disease had progressed on prior medicines and also expressed the highest levels of PD-L1. Median survival had not yet been reached.
In both studies of Atezolizumab, adverse events were consistent with those observed in previous studies.
Results from both of the studies in non-small cell lung cancer showed that measuring PD-L1 may help identify people most likely to respond to Atezolizumab, and the majority of responses continued when these data were assessed.
In February 2015, Atezolizumab received Breakthrough Therapy Designation from the US Food and Drug Administration ( FDA ) for the treatment of people whose NSCLC expresses PD-L1 and whose disease worsened during or after standard treatments ( e.g. Platinum-based chemotherapy and appropriate targeted therapy for EGFR mutation-positive or ALK-positive disease ).
Atezolizumab monotherapy vs Docetaxel in 2L/3L non-small cell lung cancer: Primary analyses for efficacy, safety and predictive biomarkers from a randomized phase II study ( POPLAR )
POPLAR is a multicentre, open-label, randomised phase II study evaluating the efficacy and safety of Atezolizumab compared with Docetaxel in people with recurrent locally advanced or metastatic NSCLC. Patients were randomised to receive either Atezolizumab 1200 mg intravenously every three weeks or Docetaxel 75 mg/m2 intravenously every three weeks.
Treatment with Atezolizumab may have been continued as long as people were experiencing clinical benefit as assessed by the investigator, i.e. in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression.
The study enrolled 287 people with previously treated, advanced NSCLC.
The primary endpoint was overall survival; secondary endpoints included progression free survival, overall response rate and safety.
People were stratified by PD-L1 expression on tumour-infiltrating immune cells ( ICs ), histology and prior lines of therapy.
PD-L1 expression was assessed for both tumour cells ( TCs ) and ICs; people were scored as TC0, 1, 2 or 3 and IC0, 1, 2 or 3 with an immunohistochemistry ( IHC ) test being developed by Roche Diagnostics.
Phase II, single-arm trial ( BIRCH ) of Atezolizumab as first-line or subsequent therapy for locally advanced or metastatic, PDL1-selected NSCLC
BIRCH is an open-label, multicentre, single-arm phase II study that evaluated the safety and efficacy of Atezolizumab in 667 people with locally advanced or metastatic NSCLC whose disease expressed. PD-L1. PD-L1 expression was assessed for both TCs and tumour-infiltrating ICs with an investigational immunohistochemistry test ( IHC ) being developed by Roche Diagnostics.
Eligibility criteria included people whose tumours were determined to express PD-L1 with an IHC score of TC2/3 or IC2/3. People in the study received a 1200 mg intravenous dose of Atezolizumab every three weeks.
The primary endpoint of the study was the overall response rate assessed by independent review facility per RECIST v1.1. Secondary endpoints included duration of response, overall survival, progression-free survival and safety.
Atezolizumab ( anti-PDL1; MPDL3280A ) is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. Atezolizumab is designed to target PD-L1 expressed on TCs and tumour-infiltrating ICs, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PDL1, Atezolizumab may activate T cells.
All studies of Atezolizumab include the evaluation of an investigational IHC test that uses the antibody SP142 to measure PD-L1 expression on both TCs and tumour-infiltrating ICs.
The goal of PD-L1 as a biomarker is to identify those people most likely to benefit when treated with Atezolizumab alone, and to determine which people may benefit most from a combination of atezolizumab and another medicine. ( Xagena )
Source: Roche, 2015