Regulatory Decision Summary for TAGRISSO

The clinical efficacy and safety data derived from two pivotal Phase II studies (AURAex and AURA2), and supportive study data, show promising evidence of clinical benefit of Tagrisso (osimertinib) 80 mg once-daily oral tablet in the target patient population, as manifested by the primary endpoint, objective response rate (ORR). Survival rates of patients with advanced NSCLC who progress on or after treatment with EGFR TKI remain very low. These patients have median overall survival from 1 to 2 years and typically experience debilitating symptoms of the disease. Currently, there are no market authorized therapies that have demonstrated efficacy against the acquired T790M TKI-resistance-conferring mutation. While the risks of toxicity associated with Tagrisso are substantial, they are outweighed by the clinical benefit of Tagrisso in this patient population with very limited effective treatment options.

Overall, Tagrisso demonstrates a favourable benefit/risk profile based on promising evidence of clinical efficacy and acceptable safety profile for the proposed indication. Accordingly, this submission is considered to be acceptable for approval under the Notice of Compliance with Conditions Guidance. In order to confirm the clinical benefit of Tagrisso for the proposed indication, AstraZeneca Canada Inc. has agreed to submit to Health Canada a Supplemental New Drug Submission-Confirmatory (SNDS-C) which will include results from the following confirmatory trials:

• AURA3; a randomized Phase III study comparing Tagrisso 80 mg versus platinum-based doublet chemotherapy in patients with locally advanced or metastatic T790M mutation-positive NSCLC who progress on prior EGFR TKI therapy.
• AURAex; a Phase II single-arm, open-label, non-randomized study extension to AURA in patients with locally advanced or metastatic T790M mutation-positive NSCLC who progress on prior EGFR TKI therapy.
• AURA2; a Phase II single-arm, open-label, non-randomized study to replicate the efficacy and safety data observed in the AURAex study.

The results of the Phase III study (AURA3) would be used to further support the clinical efficacy of Tagrisso (confirmed by statistically significant increase in progression-free survival (PFS) and providing there is no detriment to overall survival), for the proposed indication, as the study patient population reflects the target population. The final results of Phase II studies (AURAex and AURA2) would be used to support long-term clinical efficacy of Tagrisso (confirmed by a sustained and substantial ORR, and providing there is no detriment to overall survival), for the proposed indication.

For more information on Health Canadas decision, please view the Summary Basis of Decision.