Type of information: Granting of a Market Authorisation in the EU
Product name: Imfinzi®
Therapeutic area: Cancer - Oncology
- monoclonal antibody/immune checkpoint inhibitor. Durvalumab (MEDI4736) is a human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. MEDI4736 blocks these signals, countering the tumour’s immune-evading tactics.This antibody is directed against B7-H1, have been shown to block the interaction between B7-H1 and its receptors, PD-1 and CD80 (B7-1). This blockade may help to overcome the immunosuppressive effects of B7-H1 on anti-tumor T cells.
- AstraZeneca received accelerated approval from the US FDA for Imfinzi® in previously treated patients with advanced bladder cancer. Imfinzi® is approved for unresectable, Stage III NSCLC in the US, Canada, Switzerland, India, Japan, and Brazil based on the Phase III PACIFIC trial. Imfinzi® is also approved for the treatment of patients with locally-advanced or metastatic urothelial carcinoma in the US, Canada, Brazil, Israel, Hong Kong, and India.
- 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 first or second-line treatment for patients with NSCLC, small-cell lung cancer, locally-advanced or metastatic urothelial carcinoma, head and neck cancer and other solid tumours.
Company: AstraZeneca (UK)
- locally-advanced, unresectable non-small cell lung cancer (NSCLC) whose disease has not progressed following platinum-based chemoradiation therapy
- • On September 24, 2018, the European Commission has granted marketing authorisation for Imfinzi® (durvalumab) as monotherapy for the treatment of locally-advanced, unresectable non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on ? 1% of tumour cells and whose disease has not progressed following platinum-based chemotherapy and radiation therapy (CRT). The approval is based on results from the Phase III PACIFIC trial.
- The most common adverse reactions (greater than or equal to 20% of patients) of Imfinzi versus placebo were cough (40.2% vs. 30.3%), upper respiratory tract infections (26.1% vs 11.5%) and rash (21.7% vs 12.0%). 12.8% of patients experienced a grade 3 or 4 AE with Imfinzi vs 9.8% with placebo.
- • On July 26, 2018, the Committee for Medicinal Products for Human Use (CHMP) 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 ? 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. In the PACIFIC trial, Imfinzi ® 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.
- • On July 2, 2018, AstraZeneca and MedImmune announced 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). 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).
- • On February 16, 2018, the FDA approved Imfinzi® (durvalumab) for the treatment of patients with stage III non-small cell lung cancer (NSCLC) whose tumors are not able to be surgically removed (unresectable) and whose cancer has not progressed after treatment with chemotherapy and radiation (chemoradiation).
“This is the first treatment approved for stage III unresectable non-small cell lung cancer to reduce the risk of the cancer progressing, when the cancer has not worsened after chemoradiation,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
- The approval of Imfinzi® for the treatment of stage III, unresectable NSCLC was based on a randomized trial of 713 patients whose cancer had not progressed after completing chemotherapy and radiation (PACIFIC trial). The trial measured the length of time the tumors did not have significant growth after starting treatment with Imfinzi or a placebo (progression-free survival). The median progression-free survival for patients taking Imfinzi® was 16.8 months compared to 5.6 months for patients receiving a placebo. In addition, the sponsor has agreed to a post-marketing commitment to provide additional information from their study to the FDA about how long patients lived following treatment with Imfinzi after chemotherapy and radiation (overall survival).
- Common side effects of Imfinzi® in patients with stage III unresectable NSCLC include cough, fatigue, inflammation in the lungs (pneumonitis/radiation pneumonitis), upper respiratory tract infections, difficulty breathing (dyspnea) and rash. Serious risks of Imfinzi® include immune-mediated side effects, where the body’s immune system attacks healthy cells or organs, such as the lungs (pneumonitis), liver (hepatitis), colon (colitis), hormone-producing glands (endocrinopathies) and kidneys (nephritis). Other serious side effects of Imfinzi include infection and infusion-related reactions. Imfinzi can cause harm to a developing fetus; women should be advised of the potential risk to the fetus and to use effective contraception.
- • On October 9, 2017, AstraZeneca 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 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.
- • On July 31, 2017, AstraZeneca and MedImmune, its global biologics research and development arm, announced that the FDA has granted Breakthrough Therapy Designation for Imfinzi® (durvalumab) for the treatment of patients with locally-advanced, unresectable non-small cell lung cancer (NSCLC) whose disease has not progressed following platinum-based chemoradiation therapy.
- The Breakthrough Therapy Designation for Imfinzi® was granted on the basis of interim results from the Phase III PACIFIC trial, a randomised, double-blinded, placebo-controlled multi-centre trial of Imfinzi® as sequential treatment in patients with locally-advanced, unresectable (Stage III) NSCLC who had not progressed following standard platinum-based chemotherapy concurrent with radiation therapy. This is the fourth Breakthrough Therapy Designation AstraZeneca has received from the FDA for a New Oncology cancer medicine over the past three years, the second for Imfinzi®.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2018-02-16
UE authorization: 2018-09-24
Favourable opinion UE: 2018-07-26
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: