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Incyte Corporation Retifanlimab Oncologic Drugs Advisory

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Incyte Corporation Retifanlimab Oncologic Drugs Advisory Retifanlimab Incyte Corporation Oncologic Drugs Advisory Committee TABLE OF CONTENTS Table of Contents ............................................................................................................ 2 List of Tables ............................................................................................................... 5 List of Figures .............................................................................................................. 6 List of Abbreviations .................................................................................................... 7 1. Executive Summary ................................................................................................. 9 1.1. Introduction – Anal Cancer is an Important Unmet Medical Need..................... 9 1.2. Rationale for Developing Retifanlimab in Anal Cancer ................................... 10 1.2.1. Retifanlimab is a Well-Characterized PD-1 Inhibitor .................................. 10 1.2.2. Biologic Rationale for Retifanlimab ............................................................ 11 1.3. Pivotal Study: POD1UM-202 ........................................................................... 12 1.3.1. Study Design ............................................................................................. 12 1.3.2. Study Population ....................................................................................... 12 1.3.3. Efficacy Results ......................................................................................... 13 1.3.4. Safety Findings .......................................................................................... 16 1.4. Confirmatory Study: POD1UM-303 ................................................................. 17 1.5. Benefit/Risk Assessment ................................................................................ 18 1.6. Fulfillment of Criteria for Accelerated Approval ............................................... 19 2. Background on Squamous Carcinoma of the Anal Canal ...................................... 21 2.1. Overview of Squamous Carcinoma of the Anal Canal .................................... 21 2.1.1. Epidemiology and Risk Factors ................................................................. 21 2.1.2. Clinical Presentation .................................................................................. 22 2.2. Treatment of Localized Disease ...................................................................... 22 2.3. Treatment of Advanced Disease ..................................................................... 22 2.3.1. Subsequent Therapies............................................................................... 23 2.4. Disease Burden and Patient Quality of Life .................................................... 24 2.5. Patient Unmet Medical Need .......................................................................... 25 2.5.1. PD-1 Inhibitor Usage Analysis in Advanced SCAC ................................... 25 2.5.1.1. Claims Databases ............................................................................... 26 2.5.1.2. Clinical Practice Databases ................................................................ 26 2.5.1.3. Qualitative Surveys ............................................................................. 27 2.5.2. Conclusions ............................................................................................... 28 3. Rationale for Use of Retifanlimab in Advanced Squamous Carcinoma of the Anal Canal ............................................................................................................................. 29 Page 2 of 82 Retifanlimab Incyte Corporation Oncologic Drugs Advisory Committee 3.1. Unique and Favorable Biology of HPV-Driven Malignancies for Immunotherapy Treatment .................................................................................................................. 29 3.2. PD-(L)1 Inhibitors Are Effective in HPV-Driven Malignancy ............................ 30 3.3. Retifanlimab Product Overview ....................................................................... 31 3.3.1. Proposed Indication ................................................................................... 31 3.3.2. Mechanism of Action ................................................................................. 31 3.3.3. Clinical Pharmacology and Dosing Justification ........................................ 32 3.3.4. Clinical Activity of Retifanlimab in Cervical Cancer .................................... 32 4. Retifanlimab Development Plan ............................................................................. 34 4.1. Retifanlimab Development Plan ...................................................................... 34 4.1.1. Retifanlimab for Squamous Carcinoma of the Anal Canal ......................... 35 5. Regulatory History .................................................................................................. 37 5.1. Regulatory Milestones .................................................................................... 37 5.1.1. Accelerated Approval ................................................................................ 37 6. Clinical Efficacy ...................................................................................................... 38 6.1. POD1UM-202 Design ..................................................................................... 38 6.1.1. Overview .................................................................................................... 38 6.1.2. Efficacy Endpoints ..................................................................................... 39 6.1.3. Enrollment Criteria ..................................................................................... 39 6.1.4. Statistical Analysis Methods ...................................................................... 41 6.1.4.1. Sample Size ........................................................................................ 41 6.1.4.2. Analysis Populations ........................................................................... 41 6.1.4.3. Missing Data ....................................................................................... 41 6.2. POD1UM-202 Patients ................................................................................... 42 6.2.1. Disposition ................................................................................................. 42 6.2.2. Demographics ........................................................................................... 42 6.2.3. Baseline Disease Characteristics .............................................................. 43 6.2.4. Post-Progression Therapy ......................................................................... 45 6.3. POD1UM-202 Results .................................................................................... 46 6.3.1. Primary Endpoint: Objective Response Rate by ICR ................................. 46 6.3.2. Change in Measurable Tumor Burden by ICR ........................................... 48 6.3.3. Change in Measurable Liver Tumor Burden by ICR .................................. 49 6.3.4. Duration of Response by ICR .................................................................... 50 6.3.5. Durability of Stable Disease ....................................................................... 50 Page 3 of 82 Retifanlimab Incyte Corporation Oncologic Drugs Advisory Committee 6.3.6. Overall Survival ......................................................................................... 51 6.3.6.1. Overall Survival by Response Category .............................................. 52 6.3.7. Progression-Free Survival ......................................................................... 53 6.4. Efficacy Conclusions ....................................................................................... 54 7. Clinical Safety ........................................................................................................ 55 7.1. Safety Populations and Treatment Exposure .................................................. 55 7.2. Overview of Adverse Events ........................................................................... 56 7.3. Common Adverse Events ............................................................................... 57 7.4. Adverse Events Leading to Dose Delay .......................................................... 58 7.5. Adverse Events Leading to Discontinuation .................................................... 58 7.6. Serious Adverse Events .................................................................................. 59 7.7. Adverse Events with a Fatal Outcome ............................................................ 60 7.8. Immune-Related Adverse Events ................................................................... 60 7.9. Infusion-Related Reactions ............................................................................. 61 7.10. Laboratory Parameters ................................................................................ 62 7.11. Immunogenicity ........................................................................................... 63 7.12. Safety in Subgroups .................................................................................... 63 7.12.1. Safety in Patients Known to be HIV-Positive .......................................... 63 7.13. Safety Conclusions .....................................................................................
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