Type of information: Granting of a Market Authorisation in the US
Product name: Imfinzi® - durvalumab (MEDI4736)
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.
Company: AstraZeneca (UK)
Disease: locally advanced or metastatic urothelial carcinoma
- • On May 1, 2017, the FDA granted accelerated approval to durvalumab (Imfinzi®) for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. The FDA also approved the Ventana PD-L1 (SP263) Assay (Ventana Medical Systems) as a complementary diagnostic for the assessment of the PD-L1 protein in formalin-fixed, paraffin-embedded urothelial carcinoma tissue.
- Approval was based on one single-arm trial of 182 patients with locally advanced or metastatic urothelial carcinoma whose disease progressed after prior platinum-containing chemotherapy. Durvalumab, 10 mg/kg intravenously, was administered every 2 weeks. Confirmed objective response rate (ORR) as assessed by blinded independent central review per RECIST 1.1, was 17.0% (95% CI: 11.9, 23.3). At the data cutoff for the ORR analysis, median response duration was not reached (range: 0.9+ to 19.9+ months). ORR was also analyzed by PD-L1 expression status as measured by VENTANA PD-L1 (SP263) Assay. In the 182 patients, the confirmed ORR was 26.3% (95% CI: 17.8, 36.4) in 95 patients with a high PD-L1 score and 4.1% (95% CI: 0.9, 11.5) in 73 patients with a low or negative PD-L1 score.
- The most common adverse reactions in at least 15% of patients were fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, peripheral edema, and urinary tract infection. Grade 3-4 adverse events were seen in 43% of patients. Infection and immune-related adverse events such as pneumonitis, hepatitis, colitis, thyroid disease, adrenal insufficiency, and diabetes were also seen with durvalumab.
- The recommended dose of durvalumab is 10 mg/kg, administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.
- As a condition of the accelerated approval, AstraZeneca is required to complete an ongoing clinical trial to confirm clinical benefit of durvalumab. FDA approved this application approximately 6 weeks ahead of the goal date.
- This is the first approval for Imfinzi. This immune checkpoint inhibitor is also under investigation in the Phase III DANUBE trial as 1st- line treatment in urothelial carcinoma as monotherapy and in combination with tremelimumab.
- • On February 17, 2016, AstraZeneca and MedImmune announced that the FDA has granted Breakthrough Therapy designation for durvalumab (MEDI4736), an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1), for the treatment of patients with PD-L1 positive inoperable or metastatic urothelial bladder cancer whose tumour has progressed during or after one standard platinum-based regimen. The Breakthrough Therapy designation for durvalumab was granted by the FDA on the basis of early clinical data from a Phase I trial (Study 1108) in patients with advanced metastatic urothelial bladder cancer whose tumour has progressed during or after one standard platinum-based regimen. This represents the third Breakthrough Therapy designation AstraZeneca has received from the FDA for medicines in Oncology. This designation offers the opportunity for further collaboration with the FDA for the durvalumab development programme. Data from study 1108 have been submitted for presentation at a future medical meeting. Durvalumab is also being tested in first-line bladder cancer as a monotherapy as well as in combination with tremelimumab as part of the DANUBE Phase III trial which achieved first patient in during the final quarter of 2015.
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: 2017-05-01
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