FDA Grants Priority Review for Less Frequent, Fixed Dose of Durvalumab

The FDA has accepted and granted priority review to the supplemental biologics license application (sBLA) for durvalumab (Imfinzi) for a new 4-week, fixed-dose regimen for treatment in the approved indications of non-small cell lung cancer (NSCLC) and bladder cancer, according to AstraZeneca, the developer of the agent.¹

If approved by the FDA, durvalumab could be administered intravenously every 4 weeks at a fixed dose of 1500 mg in unresectable stage III NSCLC after chemoradiation therapy and previously treated advanced bladder cancer, consistent with the already approved dosing in extensive-stage small cell lung cancer (ES-SCLC).

A Prescription Drug User Fee Act date was set by the FDA for the fourth quarter of 2020.

“The new less-frequent dosing option for non-small cell lung cancer and bladder cancer will simplify and improve treatment by enabling continuity of care while minimizing the risk of exposure to infection in the healthcare setting,” Dave Fredrickson, executive vice president of the Oncology Business Unit at AstraZeneca, said in a press release. “This takes on particular urgency during the current pandemic, as doctors care for patients at high risk of COVID-19 complications. We are working with health authorities in the US and other countries to bring the option of four-week, fixed dosing for [durvalumab] to patients around the world as soon as we can.”

If approved, the new dosing of durvalumab will be available as an alternative to the approved weight-based dosing of 10 mg/kg every 2 weeks.

The sBLA was based on data from several clinical trials evaluating the safety and efficacy of durvalumab, including results observed from the phase 3 CASPIAN trial in ES-SCLC which used the 4-week, fixed-dose regimen during maintenance.

Specifically, the CASPIAN study demonstrated that individuals receiving durvalumab plus chemotherapy had a 27% lower risk of death.² The median overall survival (OS) was 13.0 months for durvalumab plus chemotherapy versus 10.3 months for chemotherapy alone.

An additional analysis of the study also found that 68% of people taking durvalumab plus chemotherapy saw their tumors shrink, compared with 58% of people taking chemotherapy alone.

The most common adverse events experienced by 20% or more of patients with extensive-stage SCLC taking durvalumab were nausea, fatigue/asthenia, and alopecia.

Currently, durvalumab is approved in the curative-intent setting of unresectable, stage III NSCLC after chemoradiation therapy in the US, Japan, China, across the EU, and in many other countries, based on the phase 3 PACIFIC trial. The agent is also approved for previously treated patients with advanced bladder cancer in the US and several other countries. Additionally, durvalumab is approved in the US and under review in Japan and other countries for ES-SCLC. Recently, durvalumab was also recommended for marketing authorization in the EU for this indication.

Notably, as part of a broad development program, AstraZeneca indicated durvalumab is being tested as a monotherapy and in combination with tremelimumab as a treatment for patients with NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, cervical cancer, and other solid tumors.

References:

1. Imfinzi granted FDA Priority Review for less-frequent, fixed-dose use [news release]. Published August 18, 2020. Accessed August 18, 2020. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/imfinzi-granted-fda-priority-review-for-less-frequent-fixed-dose-use.html

2. IMFINZI® (durvalumab) APPROVED IN THE US TO TREAT EXTENSIVE-STAGE SMALL CELL LUNG CANCER [news release]. Wilmington, Delaware. Published March 30, 2020. Accessed August 18, 2020. http://www.multivu.com/players/English/8708451-astrazeneca-imfinzi-fda-approval/