AstraZeneca has won FDA approval for its advanced bladder cancer candidate Imfinzi™ (durvalumab), which the pharma giant declared will be the cornerstone of an “extensive” immuno-oncology program across multiple cancer types and stages of disease.

Imfinzi is a human monoclonal antibody designed to work by blocking programmed death ligand-1 (PD-L1) interaction with both programmed cell death protein 1 (PD-1) and CD80 on T cells, countering the tumor's immune-evading tactics and activating the patient's immune system to attack the cancer.

Imfinzi is indicated for patients with locally advanced or metastatic urothelial carcinoma (mUC) 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.

AstraZeneca acknowledged that continued approval for that indication may hinge upon verification and description of clinical benefit in confirmatory trials.

The FDA approved Imfinzi under its accelerated approval pathway, based on tumor response rate and durability of response data from a single Phase I/II trial.

Study 1108 assessed the safety and efficacy of Imfinzi in patients with locally advanced or metastatic urothelial carcinoma of the bladder. Patients had progressed while on or after a platinum-containing chemotherapy, including those who progressed within 12 months of receiving therapy in a neoadjuvant or adjuvant setting. 

Imfinzi showed an objective response rate (ORR) of 17.0% in all evaluable patients, regardless of PD-L1 status, and 26.3% in patients with PD-L1 high-expressing tumors, AstraZeneca said. PD-L1 high was defined as 25% of tumor cells (TC) or tumor-infiltrating immune cells (IC) expressing membrane PD-L1 if ICs involved >1% of the tumor area, or TC25% or IC=100% if ICs involved 1% of the tumor area.

Approximately 14.3% of all evaluable patients achieved partial response and 2.7% achieved complete response. Of patients who had received only neoadjuvant or adjuvant therapy prior to trial entry, 9 patients (24%) responded. Based on a secondary endpoint in this single-arm trial, median time to response was 6 weeks.

Among the total 31 responding patients, 14 patients (45%) had ongoing responses of 6 months or longer, while 5 patients (16%) had ongoing responses of 12 months or longer.

Imfinzi is also under study in the Phase III DANUBE trial as first-line treatment in urothelial cancer as monotherapy, and in combination with tremelimumab.

“This first approval for Imfinzi is an important milestone in our return to growth and brings us another step closer to our goal of redefining the way cancer is treated,” AstraZeneca CEO Pascal Soriot said in a statement. “Imfinzi is the cornerstone of our extensive Immuno-Oncology program, in development across many tumor types, as monotherapy and in combination.”

That program also includes the closely-watched Phase III global MYSTIC study assessing the combination of Imfinzi and tremelimumab, a selective human antibody directed against cytotoxic T- lymphocyte-associated protein 4 (CTLA-4)—a similar treatment approach to Bristol-Myers Squibb’s marketed cancer immunotherapy Yervoy® (ipililumab).

In January, AstraZeneca added as endpoints to MYSTIC overall survival (OS) and progression-free survival (PFS) in durvalumab monotherapy. The trial is now designed to assess PFS and OS in patients with PD-L1-expressing tumors for both durvalumab monotherapy and the combination of durvalumab + tremelimumab, as well as in “all comers” patients for the combination versus standard-of-care chemotherapy.

AstraZeneca has said it anticipates releasing MYSTIC PFS data in mid 2017 and final OS data in 2018 at the latest. MYSTIC also includes several undisclosed interim analyses for OS.








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