On July 2, 2018 AstraZeneca and MedImmune, its global biologics research and development arm, reported that the Japanese Ministry of Health, Labour and Welfare approved Imfinzi (durvalumab) as maintenance therapy after definitive chemoradiation therapy (CRT) in locally-advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, JUL 2, 2018, View Source [SID1234527536]).

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Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit said: "Non-small cell lung cancer is a leading cause of death in Japan, and we are dedicated to bringing new treatment options to patients as quickly as possible. As the only immunotherapy approved in the curative-intent, Stage III lung cancer setting, Imfinzi has the potential to change the treatment paradigm for patients diagnosed with this disease."

The approval of Imfinzi is based on positive progression-free survival (PFS) data from the Phase III PACIFIC trial in unresectable Stage III NSCLC. In the trial, Imfinzi demonstrated an improvement in median PFS of 11.2 months compared to placebo. Imfinzi improved other meaningful outcomes such as time to distant metastasis or death and overall response rates. Detailed results of the PACIFIC trial were published in the New England Journal of Medicine (NEJM).

1 Blinded Independent Central Review (BICR).

2 Among the ITT population, 7% in the Imfinzi arm and 10% in the placebo arm had non-measurable disease as assessed by BICR according to RECIST v1.1.

3 Stratified by sex, age, and smoking history.

4 Pike estimator.

5 Compared with allocated α of 0.0104 (Lan DeMets spending function approximating O’Brien Fleming boundary) for interim analysis.

The incidence and severity of adverse events were comparable for patients receiving Imfinzi vs. patients receiving placebo. The most frequent adverse reactions were rash which occurred in 73 subjects (15.4%), hypothyroidism which occurred in 50 subjects (10.5%), diarrhoea which occurred in 46 subjects (9.7%) and interstitial lung disease which occurred in 46 subjects (9.7%).

In May 2018, AstraZeneca announced that the PACIFIC trial met its second primary endpoint, showing statistically-significant and clinically-meaningful overall survival (OS) in patients receiving Imfinzi compared to placebo. Full results will be presented at a forthcoming medical meeting.

Imfinzi is also approved in the US, Canada, Switzerland and India based on the Phase III PACIFIC trial. Regulatory reviews in the EU and other jurisdictions are ongoing with an EU decision expected in the second half of 2018.

About Stage III NSCLC

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. Before the PACIFIC trial, the standard of care was chemotherapy and radiation therapy, followed by active surveillance to monitor for progression.

About PACIFIC

The PACIFIC trial is a randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi as treatment in patients with Stage III unresectable NSCLC whose disease has not progressed following platinum-based chemoradiation therapy (CRT).

The trial has been 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, and duration of response.

About Imfinzi

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.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with chemotherapy, radiation therapy, small molecules, and tremelimumab, an anti-CTLA4 monoclonal antibody, as a 1st-line treatment for patients with NSCLC, small cell lung cancer, locally-advanced or metastatic urothelial carcinoma, head and neck cancer and other solid tumours.