FDA Grants Priority Review to sBLA for Durvalumab in Limited-Stage SCLC

The regulatory agency has set a Prescription Drug User Fee Act date in the fourth quarter of 2024 for its decision on approving durvalumab in this patient population.The regulatory agency has set a Prescription Drug User Fee Act date in the fourth quarter of 2024 for its decision on approving durvalumab in this patient population.

The FDA has granted priority review to a supplemental biologics license application (sBLA) for durvalumab (Imfinzi) as a treatment for patients with limited-stage small cell lung cancer (LS-SCLC) who have not experienced disease progression following platinum-containing concurrent chemoradiotherapy (cCRT), according to a press release from the developer, AstraZeneca.¹

The regulatory agency has set a Prescription Drug User Fee Act date in the fourth quarter of 2024 for its decision on approving durvalumab in this patient population.

“This priority review reinforces the potential of [durvalumab] to transform outcomes for patients as the first and only immunotherapy to demonstrate a survival benefit in [LS-SCLC],” Susan Galbraith, executive vice president of Oncology Research & Development at AstraZeneca, said in the press release.¹ “There is an urgent need for new treatment options that improve upon the standard of care in this setting, which has not changed in 40 years, and we look forward to working with the FDA to bring [durvalumab] to patients as quickly as possible.”

Supporting data for the sBLA in this indication came from the phase 3 ADRIATIC trial (NCT03703297) assessing durvalumab monotherapy and durvalumab plus tremelimumab (Imjudo) compared with placebo among patients with LS-SCLC who have not progressed on cCRT. Investigators presented updated findings from the ADRIATIC trial at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.²

Data showed that the estimated median overall survival (OS) was 55.9 months (95% CI, 37.3-not estimable [NE]) with durvalumab vs 33.4 months (95% CI, 25.5-39.9) in the placebo arm (HR, 0.73; 95% CI, 0.57-0.93; P = .0104). At 3 years, the estimated OS rate was 57% and 48% in each respective treatment arm.

Treatment with durvalumab produced a median progression-free survival (PFS) of 16.6 months (95% CI, 10.2-28.2) compared with 9.2 months (95% CI, 7.4-12.9) with placebo (HR, 0.76; 95% CI, 0.61-0.95; P = .0161). The estimated 2-year PFS rates were 46% vs 34%, respectively.

The PFS and OS benefits with durvalumab appeared to be consistent across key prespecified subgroups based on characteristics such as age, sex, disease stage at diagnosis, race, and prior radiation.

The safety profile of durvalumab in ADRIATIC was comparable with prior reports of the agent, and investigators observed no new safety signals. Grade 3/4 adverse effects occurred in 24.4% of the durvalumab arm compared with 24.2% of the placebo arm.

“The ADRIATIC results represent a breakthrough in [LS-SCLC], a highly aggressive disease where recurrence rates are high and only 15% to 30% per of patients survive 5 years,” trial investigator David R. Spigel, MD, chief scientific officer at Sarah Cannon Research Institute, said in a press release on these findings.³ “Durvalumab is the first systemic treatment to show improved survival for these patients in decades and should become a new standard of care in this setting.”

In the experimental arms of the double-blind, multi-center ADRIATIC trial, patients were assigned to receive durvalumab at 1500 mg with or without tremelimumab at 75 mg every 4 weeks for a maximum of 4 doses per cycle each followed by durvalumab every 4 weeks for a maximum of 24 months.

The trial’s primary end points were PFS and OS for durvalumab monotherapy compared with placebo. Secondary end points included OS and PFS for durvalumab/tremelimumab vs placebo, safety, and quality of life.

Overall, investigators of the ADRIATIC trial assessed 730 patients with LS-SCLC. Assessments took place at 164 treatment centers in 19 countries across North America, South America, Europe, and Asia.

References

1. Imfinzi granted priority review and breakthrough therapy designation for patients with limited-stage small cell lung cancer in the US. News release. AstraZeneca. August 15, 2024. Accessed August 15, 2024. https://tinyurl.com/4wau2n9e
2. Spigel DR, Cheng Y, Cho BC, et al. ADRIATIC: durvalumab (D) as consolidation treatment (tx) for patients (pts) with limited-stage small-cell lung cancer (LS-SCLC). J Clin Oncol. 2024;42(suppl 17):LBA5. doi:10.1200/JCO.2024.42.17_suppl.LBA5
3. Imfinzi is first and only immunotherapy to show survival benefit in limited-stage small cell lung cancer in global Phase III trial, reducing the risk of death by 27% vs. placebo. News release. AstraZeneca. June 2, 2024. Accessed August 15, 2024. https://tinyurl.com/2u6uh9fv