Results from a phase I open-label study that showed the investigational cancer immunotherapy MPDL3280A ( anti-PDL1 ) shrank tumours ( overall response rate ) in 43% ( 13/30 ) of people previously treated for metastatic urothelial bladder cancer ( UBC ) whose tumours were characterised as PD-L1 ( Programed Death Ligand-1 ) positive by a test being developed by Roche, were presented.
Adverse events were consistent with what has been previously reported for MPDL3280A. There were no severe ( grade 4-5 ) treatment related adverse reactions.
The FDA ( Food and Drug Administration ) has granted MPDL3280A Breakthrough Therapy Designation. This designation is designed to expedite the development and review of medicines intended to treat serious diseases and to help ensure patients have access to them through FDA approval as soon as possible.
The phase I study is a single-arm, multi-center, open-label trial with a cohort of 68 people with previously treated, metastatic bladder cancer. The study included 30 patients who were identified as PD-L1 positive ( immunohistochemistry [ IHC ] 2/3 ) using an investigational PD-L1 diagnostic test being developed by Roche.
After six weeks of follow-up, the objective response rate ( ORR ) as measured by RECIST criteria was 43% ( 13/30 ), and after 12 weeks, ORR was 52% ( 13/25 ) in people with PD-L1-positive tumours.
A complete response ( no radiographic evidence of tumour ) was observed in 7% of PD-L1-positive patients ( 2/30 ).
The ORR was 11% ( 4/35 ) in people whose tumours were identified as PD-L1-negative ( IHC 0/1 ) by investigational test.
People in the study experienced a median time to response of 42 days.
Treatment-related grade 3 adverse effects occurred in 4% ( 3/68 ) of people in the study and included weakness ( asthenia; 2% ), low platelet count ( thrombocytopenia; 2% ) and low phosphate levels ( blood phosphorus decrease; 2% ).
The most common adverse reactions observed to date occurring in more than 5% of patients were decreased appetite ( 12% ), fatigue ( 12% ), nausea ( 12% ), fever ( pyrexia; 9% ) and weakness ( asthenia; 7% ).
MPDL3280A is an investigational monoclonal antibody designed to interfere with a protein called PD-L1. MPDL3280A is designed to target PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, MPDL3280A may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells.
Metastatic urothelial bladder cancer is associated with a poor prognosis and limited treatment options. Bladder cancer is the ninth most common cancer worldwide, with 430,000 new cases diagnosed in 2012 and it results in approximately 145,000 deaths globally each year.
Men are three times more likely to suffer from bladder cancer compared with women and it is also three times more common in developed countries than in less developed countries. ( Xagena )
Source: Roche, 2014