FDA Grants Priority Review to Fixed-Dose Durvalumab in NSCLC and Bladder Cancer

The FDA has accepted a Biologics License Application for a new 4-week fixed-dose regimen containing durvalumab and granted it Priority Review for the approved indications of non–small cell lung cancer, as well as bladder cancer.

The FDA has accepted a Biologics License Application for a new 4-week fixed-dose regimen containing durvalumab (Imfinzi) and granted it Priority Review for the approved indications of non–small cell lung cancer (NSCLC), as well as bladder cancer.1

Durvalumab’s developer, AstraZeneca, announced this regulatory action in a press release, noting that the new dosing schedule could reduce medical visits by half.

If the FDA approves this new dosing and schedule, durvalumab would specifically be administered intravenously every 4 weeks at a fixed dose of 1500 mg to patients with unresectable stage III NSCLC after chemoradiotherapy (CRT). In bladder cancer, the drug would be given to previously treated patients with advanced disease. This new 4-week fixed-dose treatment is consistent with the dosing approved for the treatment of patients with extensive-stage small-cell lung cancer (ES-SCLC), which is durvalumab maintenance administered every 4 weeks at a fixed-dose.

“The new less-frequent dosing option for NSCLC 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. 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 4-week fixed dosing for Imfinzi to patients around the world as soon as we can,” stated Dave Frederickson, executive vice president, Oncology Business Unit, AstraZeneca.

Durvalumab is a human monoclonal antibody that binds to PD-L1, blocking the interaction between PD-L1, PD-1, and CD80. The drug is known to inhibitor immune response in patients with various solid tumors, including NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, and cervical cancer.

Durvalumab was previously approved by the FDA in stage III NSCLC based on results from the phase 3 PACIFIC trial of durvalumab after CRT (NCT02125461). The study showed 3-year survival rates that proved the agents’ long-tern clinical benefit following CRT.2

PACIFIC included 713 patients of which 709 were treated in the study. Patients were randomized 2:1 to receive IV durvalumab 10 mg/kg (n = 473) or placebo (n = 236) every 2 weeks for up to 12 months. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of patient consent.

The 3-year overall survival (OS) benefit, overall, was consistent with the primary analysis. The 3-year follow-up report showed a 31% reduction in the risk of death (HR, 0.69; 95% CI. 0.55–0.86). The median OS was not reached [NR] in the durvalumab arm (95% CI, 38.4 months – NR) compared with 291.1 months (95% CI, 22.1-35.1) in the placebo arm. The 12-month OS rate was calculated as 83.1% (95% CI, 79.4-86.2) in the durvalumab arm versus 74.6% (95% CI, 68.5-79.7) in the placebo arm. At 24 months, the OS rate was 66.3% (95% CI, 61.8-70.4) in the durvalumab arm versus 55.5% (95% CI, 48.6-61.4) in the placebo group. Finally, the 36-month OS rate observed was 57.0% (95% CI, 53.3-61.4) in the durvalumab arm compared with 43.5% (95% CI, 37.0-49.9) in the placebo arm.

The conclusion of the study was that the long-term OS benefit further established the PACIFIC regimen as the standard of care therapy for patients with unresectable stage III NSCLC who do not progress while undergoing CRT.

Safety data from the primary analysis of PACIFIC showed grade 3/4 adverse events (AEs) in 29.9% of patients who received durvalumab and 26.1% of those in the placebo arm. The most common grade 3/4 AE observed was pneumonia, which occurred in 4.4% of the durvalumab-treated patients and 3.8% of those who were given placebo. Overall, 15.4% of the durvalumab arm and 9.5% of the placebo arm discontinued treatment due to an AE.3

In bladder cancer, durvalumab was granted FDA approval based on results from the single-arm phase I/II Study 1108. The specific indication is 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.4

A total of 182 patients were included in the study and evaluated for the coprimary end points of dose-limiting toxicities and anti-tumor efficacy.

Study 1108 demonstrated clinical activity and a tolerable safety profile, according to data presented in 2017 at the American Society of Clinical Oncology (ASCO) Annual Meeting. The objective response rate (ORR) was 26.3% (95% CI, 17.8-36.4) with durvalumab per investigator-assessed RECIST v1.1. The disease control rate observed in the study was 42.9% (95% CI, 28.8-57.8).

In terms of survival, the median progression-free survival was 4.0 months (95% CI, 2.3-9.1). The median OS was 21.0 months (95% CI, 14.5-not estimable. Investigators also recorded a 12-month OS rate of 72% (95% CI, 56-83). These responses were observed regardless of histology.

Treatment with durvalumab led to treatment-related adverse events (TRAEs) in 56% of patients. The most common TRAEs were fatigue (15%), diarrhea (13%), and decreased appetite (10%). TRAEs led to discontinuation of durvalumab in 7% of the study population.

In addition, 10% of patients experienced grade 3 or higher TRAEs.


1. Imfinzi granted FDA Priority Review for less-frequent, fixed-dose use. News release. AstraZeneca. August 18, 2020. Accessed August 18, 2020. https://bit.ly/317kaz1

2. Gray JE, Villegas A, Daniel D, et al. Three-year overall survival with durvalumab after chemoradiotherapy in stage III NSCLC—update from PACIFIC. Journal of Thoracic Oncol. 2019;14(2):288-293. doi: 10.1016/j.jtho.2019.10.002

3. Powles T, O’Donnell PH, Massard C, et al. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial CarcinomaUpdated Results From a Phase 1/2 Open-label Study. JAMA Oncol. 2017;3(9):e172411. doi:10.1001/jamaoncol.2017.2411

4. Antonia SJ, Brahmer JR, Balmanoukian AS, et al. Safety and clinical activity of first-line durvalumab in advanced NSCLC: Updated results from a Phase 1/2 study.
J Clin Oncol. 2017 35 (suppl; abstr e20504). doi: 10.1200/JCO.2017.35.15_suppl.e20504