Durvalumab granted FDA priority review for less-frequent dose in bladder cancer

The FDA has granted a priority review designation to a supplemental Biologics License Application (sBLA) for a less-frequent, fixed-dose regimen of durvalumab for its approved indications in bladder cancer and non–small cell lung cancer, according to AstraZeneca, the manufacturer of the PD-L1 inhibitor.¹

Specifically in bladder cancer, the current FDA-approved dosage is 10 mg/kg (IV infusion) every 2 weeks. If approved, the new schedule would be a fixed-dose of 1500 mg (IV infusion) administered every 4 weeks, thus reducing a patient’s required medical visits by 50%.

The FDA is scheduled to make a decision on the sBLA by the end of this year, AstraZeneca reported in a press release.

"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. 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 United States and other countries to bring the option of four-week, fixed dosing for Imfinzi to patients around the world as soon as we can,” Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca stated in the press release.

The FDA approved durvalumab in May 2017 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.²

The approval was supported by the single-arm phase I/II Study 1108, which included 182 patients with locally advanced or metastatic urothelial carcinoma. Patients had progressed following platinum-containing chemotherapy.

Among all evaluable patients, regardless of PD-L1 status, the objective response rate (ORR) per blinded independent review was 17%. Among patients with high PD-L1 expression levels (n = 95) the ORR was 26.3%, compared to 4.1% among patients with low or no PD-L1 expression (n = 73). Overall, there were 5 complete responses and 26 partial responses, which included 25 in the PD-L1–high group, 3 in the PD-L1 low/no group, and 3 among patients whose PD-L1 status was unknown.

Regarding safety, 43% of patients experienced grade 3/4 adverse events, with those occurring in at least 3% of patients consisting of fatigue, urinary tract infection, musculoskeletal pain, abdominal pain, dehydration, and general physical health deterioration.

Durvalumab was approved under the FDA’s accelerated approval program, meaning long-term approval of the drug is contingent upon the results of a confirmatory trial.

One such confirmatory trial was the phase 3 DANUBE trial (NCT02516241), which evaluated durvalumab alone or in combination with the anti–CTLA-4 agent tremelimumab against standard chemotherapy in patients with stage IV urothelial cancer. However, it was reported by AstraZeneca in March 2020³ that the study missed both of its coprimary endpoints: the durvalumab/tremelimumab combination did not improve overall survival (OS) in the all-comer overall population, and single-agent durvalumab did not lead to an OS benefit in patients with high PD-L1 expression.

Researchers now await the results of other phase 3 studies of durvalumab, including the phase 3 NILE trial (NCT03682068). In this study, patients with unresectable locally advanced or metastatic urothelial cancer are being randomized to durvalumab plus standard chemotherapy; durvalumab plus standard chemotherapy and tremelimumab; or the control arm of standard chemotherapy alone.

References

1. Imfinzi granted FDA Priority Review for less-frequent, fixed-dose use. Published online August 18, 2020. https://bit.ly/2YdsV8O. Accessed August 18, 2020

2. AstraZeneca’s Imfinzi (durvalumab) receives US FDA accelerated approval for previously treated patients with advanced bladder cancer. Published online May 1, 2017. https://bit.ly/3aAK8hd. Accessed August 18, 2020

3. Update on Phase III DANUBE trial for Imfinzi and tremelimumab in unresectable, Stage IV bladder cancer. Published online March 6, 2020. https://bit.ly/3iSQRpP. Accessed August 18, 2020