AstraZeneca Plc - Update on the Phase III NEPTUNE trial
AstraZeneca today announced final overall survival (OS) results from the Phase III NEPTUNE trial, a randomised, open-label, multi-centre, global trial of Imfinzi (durvalumab) in combination with tremelimumab, an anti-CTLA4 antibody, vs. standard-of-care (SoC) platinum-based chemotherapy in previously-untreated Stage IV (metastatic) non-small cell lung cancer (NSCLC) patients. The trial was performed in an all-comers population, and the primary analysis population was patients with a high tumour mutational burden (TMB). TMB is a measurement of the number of mutations within the genome (DNA) of a tumour, and tumours with high levels of TMB may be more visible to the immune system.1,2
In the primary analysis population of patients whose blood TMB was 20 or more mutations per megabase (mut/Mb), the combination of Imfinzi and tremelimumab did not meet the primary endpoint of improving OS compared to SoC chemotherapy. The safety and tolerability profile for the combination of Imfinzi and tremelimumab was consistent with previous trials.
José Baselga, Executive Vice President, Oncology R&D said: "We are fully committed to a deep analysis of the vast clinical and biomarker data from this trial to gain further insights to improve Immuno-Oncology approaches for patients with metastatic non-small cell lung cancer."
AstraZeneca will submit the full results for presentation at a forthcoming medical meeting.
Imfinzi is also being tested as monotherapy in the Phase III PEARL trial, and in combination with chemotherapy with or without tremelimumab in the Phase III POSEIDON trial as part of an extensive late-stage Immuno-Oncology programme in Stage IV NSCLC.
The NEPTUNE trial is a randomised, open-label, multi-centre, global, Phase III trial of Imfinzi in combination with tremelimumab vs. SoC platinum-based chemotherapy in the 1st-line treatment of patients with Stage IV (metastatic) NSCLC. The trial population included patients with non-squamous or squamous histologies, no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutation and the full range of PD-L1 expression levels. The primary endpoint was OS in patients with high blood TMB defined as ≥ 20 mut/Mb.
The trial is being conducted in more than 200 centres across 29 countries, including the US, Europe, South and Central America, the Middle East and Asia.
About Stage IV NSCLC
Lung cancer is the leading cause of cancer death among both men and women and accounts for about one-fifth of all cancer deaths.3 Lung cancer is broadly split into NSCLC and SCLC, with 80-85% classified as NSCLC.4 Stage IV is the most advanced form of lung cancer and is often referred to as metastatic disease.5 Lung cancer patients are most commonly diagnosed after the tumour has spread outside of the lung.6 For these patients with metastatic disease, prognosis is particularly poor, as only 1 in 10 will be alive five years after diagnosis.7
Imfinzi (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.
Imfinzi is approved for unresectable, Stage III NSCLC in 49 countries including the US, Japan, and across the EU, based on the Phase III PACIFIC trial. Imfinzi is also approved for previously-treated patients with advanced bladder cancer in the US, Canada, Brazil, Australia, Israel, India, United Arab Emirates, Qatar, Macau and Hong Kong.
As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, small-cell lung cancer (SCLC), bladder cancer, head and neck cancer, liver cancer, cervical cancer, biliary tract cancer and other solid tumours.