AstraZeneca, along with MedImmune, its global biologics research and development arm, has announced that the European Medicines Agency (EMA) has accepted a Marketing Authorisation Application (MAA) for Imfinzi (durvalumab) for the treatment of patients with locally-advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) whose disease has not progressed following platinum-based chemoradiation therapy. This is the first registrational submission for Imfinzi in the European Union.
The MAA submission acceptance is an important milestone for Imfinzi in a disease state where patients need better treatment options and outcomes. Currently, the standard of care for patients with this earlier stage of lung disease is active monitoring following concurrent chemoradiation.
The MAA submission is based on positive progression-free survival (PFS) data from the phase III PACIFIC trial. The trial continues to evaluate overall survival (OS), its other primary endpoint. Detailed results of the PACIFIC trial, including additional safety information, were published online in the New England Journal of Medicine.
Locally-advanced (Stage III) lung cancer is commonly divided into two stages (IIIA and IIIB), which are defined by how much the cancer has spread locally and the possibility of surgery. This differentiates it from Stage IV disease, when the cancer has spread (metastasised) to distant organs.
Stage III lung cancer represents approximately one-third of NSCLC incidence and was estimated to affect around 105,000 patients in the top-7 countries in 2016. More than 70% of these patients have tumours that are unresectable. The current standard of care is chemotherapy and radiation followed by active surveillance to monitor for progression. The prognosis remains poor and long-term survival rates are low.
The PACIFIC trial is a randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi as treatment in unselected patients with locally-advanced, unresectable (Stage III) NSCLC who have not progressed following platinum-based chemotherapy concurrent with radiation therapy.
The trial is being conducted in 235 centres across 26 countries involving approximately 700 patients. The primary endpoints of the trial are progression-free survival (PFS) and overall survival (OS), and secondary endpoints include landmark PFS and OS, objective response rate (ORR) and duration of response.
Imfinzi (durvalumab), a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumour's immune-evading tactics and inducing an immune response.
Imfinzi has already received accelerated approval in the US for the treatment of patients with locally advanced or metastatic urothelial carcinoma, who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery.
As part of a broad development programme, Imfinzi is also being investigated for the adjuvant treatment of patients with NSCLC in the CCTG (Canadian Cancer Trials Group) trial ADJUVANT (BR31). In the MYSTIC, NEPTUNE, and PEARL Phase III trials, Imfinzi is being studied for 1st-line treatment as monotherapy and/or in combination with tremelimumab, an anti-CTLA-4 monoclonal antibody, for the treatment of metastatic NSCLC. The POSEIDON trial is investigating Imfinzi with and without tremelimumab in combination with chemotherapy in the same population.
AstraZeneca is committed to developing medicines to help every patient with lung cancer. We have two approved medicines and a growing pipeline that targets genetic changes in tumour cells and boosts the power of the immune response against cancer. Our unrelenting pursuit of science aims to deliver more breakthrough therapies with the goal of extending and improving the lives of patients across all stages of disease and lines of therapy.