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1 Oncologic Drugs Advisory Committee (ODAC) Oncologic Drugs Advisory Committee (ODAC) Meeting April, 27, 2021 BLA# 761034/Supplement 18 Drug name: TECENTRIQ® (atezolizumab) Applicant: Genentech, Inc. Combined FDA and Applicant ODAC Briefing Document Advisory Committee Briefing Materials: Available For Public Release 1 DISCLAIMER STATEMENT The attached package contains background information prepared by the Applicant and the Food and Drug Administration (FDA) for the panel members of the advisory committee. The package contains assessments and/or conclusions and recommendations written by individual FDA reviewers. Such conclusions and recommendations do not necessarily represent the final position of the individual reviewers, nor do they necessarily represent the final position of the Review Division or Office. We have brought the drug TECENTRIQ® (also known as atezolizumab) to this Advisory Committee in order to gain the Committee’s insights and opinions, and the background package may not include all issues relevant to the final regulatory recommendation and instead is intended to focus on issues identified by the Agency for discussion by the advisory committee. The FDA will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized. The final determination may be affected by issues not discussed at the advisory committee meeting. 2 Table of Contents Table of Tables .......................................................................................................................... 5 Table of Figures ......................................................................................................................... 6 1. Introduction .........................................................................................................................10 1.1 Applicant Current Indication(s)...........................................................................................10 1.2 Purpose of the Meeting ....................................................................................................10 2. Efficacy ................................................................................................................................12 2.1 Description of Clinical Setting.............................................................................................12 2.1.1 Disease Setting ..........................................................................................................12 2.1.2 Unmet Need..............................................................................................................12 2.1.3 Rationale for Atezolizumab in the Treatment of TNBC .....................................................15 2.1.4 Regulatory History .....................................................................................................15 2.2 Summary of Clinical Trials Supporting Efficacy ......................................................................17 2.2.1 Study Designs ............................................................................................................17 2.2.2 Statistical Methods.....................................................................................................19 2.3 Efficacy Summary .............................................................................................................20 2.3.1 Pivotal Study: IMpassion130 ........................................................................................20 2.3.2 Confirmatory PMR Study: IMpassion131 .......................................................................27 2.4 Efficacy Conclusions .........................................................................................................30 3. Safety ..................................................................................................................................33 3.1 Exposure.........................................................................................................................33 3.2 Summary of Adverse Events ..............................................................................................34 3.2.1 Adverse Events of Special Interest ................................................................................36 3.2.2 Summary of IMpassion131 Safety Profile.......................................................................37 3.3 Safety Summary and Conclusions .......................................................................................38 4. Clinical Outcome Assessment Analyses .....................................................................................39 5. Other Significant Issues Pertinent to Clinical Conclusions on Efficacy and Safety .............................39 5.1 Issue for Discussion ..........................................................................................................39 6. Points for the Advisory Committee to Consider..........................................................................41 7. Draft Topics for Discussion by the Advisory Committee ...............................................................44 8. References ...........................................................................................................................44 9. Appendix..............................................................................................................................47 Appendix 1: Protocol and SAP Amendments..............................................................................47 Appendix 2: IMpassion130 Study Design and Hierarchical Statistical Testing Details ........................50 Appendix 3: Demographics and Baseline Characteristics Tables....................................................52 3 Appendix 4: Additional Supportive Data for IMpassion130 ..........................................................56 Appendix 5: IMpassion130 Patient–reported Outcome (PRO) Data ...............................................58 Appendix 6: Additional Supportive Data for IMpassion131 ..........................................................61 Appendix 7: Trial Design Differences between IMpassion130 and IMpassion131 ............................63 Appendix 8: Additional Safety Tables........................................................................................64 4 Table of Tables Table 1: Overview of Efficacy (PD-L1-Positive Population) in IMpassion130 ..............................22 Table 2: IMpassion130: Pre-Specified OS Analyses (PD-L1−Positive Population) .......................25 Table 3: Confirmed Overall Response Rate and Duration of Response ......................................26 Table 4: Overview of Efficacy (PD-L1-Positive Population) in IMpassion131 ..............................28 Table 5: Overview of Exposure: IMpassion130 and IMpassion131 ............................................34 Table 6: Overview of Safety: IMpassion130, IMpassion131, and the Atezolizumab Monotherapy Pooled Population ..................................................................................................................35 Table 7: Overall Summary of AESIs (Safety-Evaluable Population) ............................................37 Table 8: Summary of Deaths in IMpassion131 .........................................................................38 Table 9: Additional Ongoing Phase III Company-Sponsored Atezolizumab Studies in TNBC .......40 Table 10: Key Demographics and Baseline Characteristics in IMpassion130 ..............................52 Table 11: Key Demographics and Baseline Characteristics in IMpassion131 ..............................54 Table 12: IMpassion130 Overview of Efficacy (ITT Population) .................................................56 Table 13: IMpassion130: Time to Deterioration in Global Health Status/ HRQoL.......................59 Table 14: IMpassion131 Overview of Efficacy (ITT Population) .................................................62 Table 15: Trial Design Differences between IMpassion130 and IMpassion131 ..........................63 Table 16: Summary of AESIs by Medical Concept (Safety-Evaluable Population) .......................64 Table 17: AEs Reported in ≥10% of Patients in IMpassion130, IMpassion131, and the Atezolizumab Monotherapy Pooled Population.......................................................................65 Table 18: Overview of Safety in IMpassion130 at the Primary Analysis (CCOD 17 Apr 2018) and the Updated Analysis (CCOD 14 Apr 2020)...............................................................................67 5 Table of Figures Figure 1: Study Design for IMpassion130 .................................................................................18 Figure 2: Study Design for IMpassion131 .................................................................................19 Figure 3: IMpassion130: Kaplan-Meier Plot of Investigator-Assessed PFS (PD-L1−Positive Population) ............................................................................................................................23 Figure 4: IMpassion130: Kaplan-Meier Plot of Overall Survival (PD-L1−Positive Population): Final Analysis ..................................................................................................................................25 Figure 5: IMpassion131: Kaplan-Meier Plot of Investigator-Assessed PFS (PD-L1-Positive Population) ............................................................................................................................29 Figure
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