FDA Grants Priority Review to Durvalumab for LS-SCLC After Concurrent Chemoradiotherapy

FDA

The FDA has granted priority review to the supplemental biologics license application (sBLA) seeking the approval of durvalumab (Imfinzi) for the treatment of patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based concurrent chemoradiotherapy.¹

Additionally, the regulatory agency awarded breakthrough therapy designation to durvalumab for this indication.

The sBLA is supported by data from the phase 3 ADRIATIC trial (NCT03703297). Findings presented at the 2024 ASCO Annual Meeting showed that at a median follow-up of 37.2 months (range, 0.1-60.9), evaluable patients treated with durvalumab (n = 264) experienced a median overall survival (OS) of 55.9 months (95% CI, 37.3-not evaluable) vs 33.4 months (95% CI, 25.5-39.9) for those given placebo (n = 266; HR, 0.73; 95% CI, 0.57-0.93; P = .0104).²

Furthermore, at a median follow-up of 27.6 months (range, 0.0-55.8), durvalumab elicited 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) for placebo (HR, 0.76; 95% CI, 0.61-0.95; P = .0161).

“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 R&D at AstraZeneca, stated in a news 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.”

ADRIATIC was a randomized, double-blind, placebo-controlled, multicenter, international trial that enrolled patients with inoperable stage I to II or stage III LS-SCLC who had not experienced disease progression following platinum-based concurrent chemoradiotherapy. Patients were required to have a World Health Organization performance status of 0 or 1, and prior treatment with prophylactic cranial irradiation was permitted.²

Enrolled patients were randomly assigned to receive 1500 mg of durvalumab once every 4 weeks; placebo once every 4 weeks; or 1500 mg of durvalumab plus 75 mg of tremelimumab (Imjudo) once every 4 weeks for 4 cycles followed by 1500 mg of durvalumab once every 4 weeks. Treatment continued for up to 24 months, or until disease progression or unacceptable toxicity.

Blinded independent central review–assessed PFS per RECIST v1.1 criteria and OS for durvalumab monotherapy vs placebo served as the trial’s dual primary end points. Key secondary end points included PFS and OS for durvalumab plus tremelimumab vs placebo. OS and PFS landmarks, as well as safety, were other secondary end points.

Regarding safety, any-grade adverse effects (AEs) were reported in 94.3% of patients treated with durvalumab (n = 262) compared with 88.3% of those administered placebo (n = 265). The respective rates of grade 3/4 AEs were 24.4% and 24.2%. Serious AEs occurred in 29.8% and 24.2% of patients, respectively.

AEs led to treatment discontinuation in 16.4% of patients in the durvalumab arm vs 10.6% of patients in the placebo arm. AEs led to death in 2.7% vs 1.9% of patients, respectively. Treatment-related AEs that led to death occurred in 2 patients in the durvalumab arm, comprised of encephalopathy (n = 1) and pneumonitis (n = 1).

The rate of any-grade immune-mediated AEs was 32.1% in the durvalumab arm vs 10.2% in the placebo arm; the respective rates of grade 3/4 immune-mediated AEs were 5.3% and 1.5%.

Any-grade pneumonitis or radiation pneumonitis was reported in 38.2% of patients in the durvalumab group vs 30.2% of those in the placebo group. The rates of grade 3/4 pneumonitis were 3.1% and 2.6%, respectively.

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://www.astrazeneca.com/media-centre/press-releases/2024/imfinzi-granted-priority-review-and-breakthrough-therapy-designation-for-patients-with-limited-stage-small-cell-lung-cancer-in-the-us.html
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