Regulatory Decision Summary for Yescarta

The market authorization of Yescarta was based on the results of a pivotal, single-arm Phase I/II study ZUMA-1 in patients with relapsed for refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, DLBCL arising from follicular lymphoma and high grade B-cell lymphoma. Yescarta was administered as one-time single infusion 3 days after the conditioning regimen.

The primary efficacy endpoint was overall response rate (ORR) as assessed by an independent review committee using the 2007 revised International Working Group response criteria for malignant lymphoma. Yescarta treatment resulted in a high ORR and the response, particularly complete remission was durable. ORR was generally consistent among patient subgroups defined by demographics and disease characteristics. As relapsed or refractory large B-cell lymphoma responded poorly to conventional therapies, these ORR and DOR results in ZUMA-1 were considered clinically meaningful.

Yescarta can cause serious (sometimes life-threatening or fatal) adverse reactions. The most common serious adverse reactions reported in ZUMA-1 were cytokine release syndrome (CRS), neurologic adverse reactions and serious infections; these adverse reactions were generally manageable and reversible. Severe CRS and serious neurologic adverse reactions required prompt management to prevent life-threatening complications or death. Monitoring schemes and management algorithms were developed for these adverse reactions and are provided in the Yescarta product monograph. In order to manage the risk of serious adverse reactions, the sponsor proposed and Health Canada agreed that Yescarta should only be available through a controlled distribution plan. Safety of Yescarta will also be monitored and characterize in the post-market setting per Yescarta Risk Management Plan.

Overall, the benefit/risk profile of Yescarta is considered positive for the authorized indication.

Health Canada granted this submission priority review in accordance with the priority review policy.

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