▎WuXiEdited by Kant Content Team

Today, AstraZeneca announced that the supplemental New Drug Application (sNDA) for its epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) Tagrisso (osimertinib) has been accepted by the U.S. FDA and granted Priority Review status for the treatment of adult patients with unresectable stage III epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) who have received chemoradiation therapy (CRT).If approved, Tagrisso will be indicated for EGFRm patients whose tumors have exon 19 deletions or exon 21 (L858R) mutations.FDA is expected to complete the regulatory review in the fourth quarter of 2024.

FDA GrantsTagrisso's Priority Review Status Mainly Based OnResults of the LAURA Phase 3 clinical trial. This is a randomized, double-blind, placebo-controlled, global multicenter Phase 3 trial involving patients with Stage III EGFRm NSCLC whose tumors are unresectable and who have not experienced disease progression after receiving platinum-based CRT. Patients receive once-daily oral doses of 80 mg Tagrisso until disease progression, unacceptable toxicity, or meeting other discontinuation criteria.The detailed data of the trial were simultaneously published in The New England Journal of Medicine.

Results assessed by the blinded independent central review (BICR) showed,Compared with placebo, Tagrisso reduced the risk of disease progression or death by 84% (HR=0.16; 95% CI: 0.10-0.24; p<0.001). The median PFS for patients treated with Tagrisso was 39.1 months, compared to 5.6 months in the placebo group.The proportion of patients in the Tagrisso group and placebo group who were alive and disease-free at 12 months was 74% (95% CI: 65-80) and 22% (95% CI: 13-32), respectively. Notably,A clinically meaningful PFS benefit was observed across all predefined subgroups, including gender, race, EGFR mutation type, age, smoking history, and prior CRT.

▲Summary of Efficacy Results from the LAURA Trial (Image Source: Reference [2])

Patients in the Tagrisso group also showed a favorable trend in overall survival.At 36 months, the overall survival rates for patients in the Tagrisso group and the placebo group were 84% (95% CI: 75-89) and 74% (95% CI: 57-85), respectively. The difference was not statistically significant (HR=0.81, 95% CI: 0.42-1.56; p=0.53). However, the data were not yet mature at the time of analysis (data maturity 20%), and the trial will continue to evaluate changes in the secondary endpoint OS.

Safety results and discontinuation rates due to adverse events were as expected, with no new safety issues identified. Among patients in the Tagrisso group and the placebo group, 35% and 12%, respectively, experienced grade 3 or higher adverse events caused by various reasons.

Tagrisso is a third-generation, irreversible EGFR-TKI that has been clinically proven to be effective in NSCLC.Tagrisso Approved Indications Include First-Line Treatment for Locally Advanced or Metastatic EGFRm NSCLC, Locally Advanced or Metastatic EGFR T790M Mutation-Positive NSCLC, and Adjuvant Therapy for Early-Stage (IB, II, and IIIA) EGFRm NSCLC. In August 2023, Tagrisso in Combination with Chemotherapy Granted Breakthrough Therapy Designation by the U.S. FDA for First-Line Treatment of Adult Patients with Locally Advanced or Metastatic EGFRm NSCLC. In February this Year, Tagrisso Combined with ChemotherapyFDA Approved, for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer.

References:

[1] Tagrisso granted Priority Review in the US for patients with unresectable, Stage III EGFR-mutated lung cancer. Retrieved June 10, 2024 fromhttps://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-granted-priority-review-in-the-us-for-patients-with-unresectable-stage-iii-egfr-mutated-lung-cancer.html

[2] TAGRISSO® (osimertinib) reduced the risk of disease progression or death by 84% in patients with unresectable, Stage III EGFR-mutated lung cancer vs. placebo in LAURA Phase III trial. Retrieved June 3, 2024 from https://www.businesswire.com/news/home/20240602348345/en

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