Imfinzi Approved in US for Less-Frequent, Fixed-Dose Use

AstraZeneca’s Imfinzi (durvalumab) has been approved in the US for an additional dosing option, a 1,500mg fixed dose every four weeks, in the approved indications of unresectable Stage III non-small cell lung cancer (NSCLC) after chemoradiation therapy (CRT) and previously treated advanced bladder cancer. This new option is consistent with the approved Imfinzi dosing in extensive-stage small cell lung cancer (ES-SCLC) and will be available to patients weighing more than 30kg as an alternative to the approved weight-based dosing of 10mg/kg every two weeks.

The approval by the Food and Drug Administration (FDA) was based on data from several Imfinzi clinical trials, including the PACIFIC Phase III trial which supported the two-week, weight-based dosing in unresectable Stage III NSCLC, and the CASPIAN Phase III trial which used four-week, fixed-dosing during maintenance treatment in ES-SCLC. The decision follows the Priority Review granted by the FDA in August 2020.

“This new four-week dosing option gives doctors the choice to cut the number of visits for critical cancer treatment in half and offers a regimen that is more convenient for patients. Additionally, it limits potential exposure to infection in the healthcare environment for a population that is especially vulnerable to complications from COVID-19,” Victoria M. Villaflor, MD, Clinical Professor in the Department of Medical Oncology and Therapeutics Research at City of Hope Cancer Center, Los Angeles, California, said.

“The approval of this new dosing option across indications reflects our ongoing commitment to improve the patient experience and ensure continuity of care - a priority at all times, but especially during the pandemic. Cancer won’t wait, and it is our job to provide patients with treatment options that acknowledge the challenges the pandemic poses to cancer care, enabling them to visit their physician when truly needed and avoid preventable exposure to healthcare-associated infections,” Dave Fredrickson, Executive Vice President, Oncology Business Unit, said.

The four-week 1,500mg fixed-dosing option for Imfinzi is also under regulatory review in several other countries, including in the EU where the new dosing option was granted accelerated assessment.

Imfinzi is approved in the curative-intent setting of unresectable, Stage III NSCLC after CRT in the US, in the EU, in Japan, in China and in many other countries, based on the PACIFIC Phase III trial. Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and several other countries. Additionally, it is approved in the US, the EU, Japan and several other countries around the world for the treatment of ES-SCLC based on the CASPIAN Phase III trial.

Stage III NSCLC (locally advanced) 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, where the cancer has spread (metastasized), as the majority of Stage III patients are currently treated with curative intent.

Stage III NSCLC represents approximately one third of NSCLC incidence and in 2015 was estimated to affect nearly 200,000 patients in the following eight large countries: China, France, Germany, Italy, Japan, Spain, UK, and the US, with approximately 43,000 cases in the US alone. The majority of Stage III NSCLC patients are diagnosed with unresectable tumors. Prior to approval of Imfinzi in this setting, no new treatments beyond CRT had been available to patients for decades.

SCLC is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly, despite initial response to chemotherapy. About two thirds of SCLC patients are diagnosed with extensive-stage disease, in which the cancer has spread widely through the lung or to other parts of the body. Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis.

In 2018, approximately 550,000 people were diagnosed with bladder cancer around the world and 200,000 died from the disease. Locally advanced and metastatic bladder cancer remains an area of unmet medical need and typically only one in seven patients is alive five years after diagnosis. Urothelial cancer (UC) is the most common form of bladder cancer. UC is the 10th most common cancer worldwide and the 13th most common cause of cancer death. PD-L1 is widely expressed in tumor and immune cells in patients with bladder cancer and helps tumors evade detection from the immune system.

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 tumor’s immune-evading tactics and releasing the inhibition of immune responses.

As part of a broad development program, Imfinzi is also being tested as a monotherapy and in combinations including with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, esophageal cancer, gastric cancer, cervical cancer, ovarian cancer, endometrial cancer and other solid tumors.