The Committee for Medicinal Products for Human Use ( CHMP ) of the European Medicines Agency ( EMA ) has adopted a positive opinion, recommending a marketing authorisation of Imfinzi ( Durvalumab ) for the treatment of locally-advanced, unresectable non-small cell lung cancer ( NSCLC ) in adults whose tumours express PD-L1 on greater than or equal to 1% of tumour cells and whose disease has not progressed following Platinum-based chemotherapy and radiation therapy ( CRT ).
The recommendation is based on the progression-free survival ( PFS ) and overall survival ( OS ) primary endpoints of the phase III PACIFIC trial, and post-hoc subgroup analyses by PD-L1 expression requested by the CHMP.
Durvalumab is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.
In the PACIFIC trial, Durvalumab demonstrated a statistically-significant and clinically-meaningful improvement in PFS and OS in all-comer patients.
The recommended label reflects most of the patients in the trial with a known PD-L1 status.
Stage III ( locally advanced ) NSCLC is commonly divided into three sub-categories ( IIIA, IIIB and IIIC ), defined by how much the cancer has spread locally and the possibility of surgery.
Stage III disease is different from stage IV disease, when the cancer has spread ( metastasised ) to distant organs, as stage III is currently treated with curative intent.
Stage III NSCLC represents approximately one-third of NSCLC incidence and was estimated to affect around 105,000 patients in the top-eight countries ( China, France, Germany, Italy, Japan, Spain, UK, US ) in 2017.
The majority of stage III NSCLC patients are diagnosed with unresectable tumours.
No new treatments beyond chemoradiation therapy, followed by active surveillance to monitor for progression, have been available to patients for decades.
The PACIFIC trial is a randomised, double-blinded, placebo-controlled, multi-centre trial of Durvalumab as treatment in all-comer patients ( i.e. regardless of PD-L1 status ) with unresectable, stage III NSCLC whose disease has not progressed following Platinum-based chemotherapy and radiation therapy.
The trial is being conducted in 235 centres across 26 countries involving 713 patients.
The primary endpoints of the trial are PFS and OS, and secondary endpoints include landmark PFS and OS, objective response rate ( ORR ), and duration of response ( DoR ). ( Xagena )
Source: AstraZeneca, 2018