A Phase I/II Clinical Trial of Nivolumab and Plinabulin for Patients With Advanced Stage Non-small Cell Lung Cancer That Have Progressed Through First Line Platinum Doublet Chemotherapy
Phase: PHASE1
Conditions: ALK Gene Translocation, EGFR Activating Mutation, Recurrent Non-Small Cell Lung Carcinoma, ROS1 Gene Translocation, Stage IIIB Non-Small Cell Lung Cancer AJCC v7, Stage IV Non-Small Cell Lung Cancer AJCC v7
Sponsor: University of Washington

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1. 
Summary ...............................................................................................................................3 
2. 
Background ...........................................................................................................................4 
2.1. 
Plinabulin ..................................................................................................................................... 4 
2.2. 
Nivolumab.................................................................................................................................... 5 
2.3. 
Microtubule depolymerizing  agents as immunomodulators. ..................................................... 6 
3. 
Trial Objectives ......................................................................................................................7 
3.1. 
Primary Objective. ....................................................................................................................... 7 
3.2. 
Secondary Objectives. .................................................................................................................. 7 
3.3. 
Translational objectives. .............................................................................................................. 7 
4. 
Study population and selection of subjects. ............................................................................7 
4.1. 
Inclusion criteria .......................................................................................................................... 7 
4.2. 
Exclusion criteria .......................................................................................................................... 8 
5. 
Trial design and treatment plan. .............................................................................................9 
5.1. 
Trial design .................................................................................................................................. 9 
5.2. 
Endpoints ..................................................................................................................................... 9 
5.3. 
Dose rationale ............................................................................................................................ 10 
5.4. 
Treatment plan .......................................................................................................................... 10 
6. 
Study Conduct and trial procedures ...................................................................................... 11 
6.1. 
Screening ................................................................................................................................... 11 
6.2. 
Biopsy......................................................................................................................................... 12 
6.3. 
Treatment on Days 1 and 15 of each Cycle. .............................................................................. 12 
6.4. 
Drug Administration .................................................................................................................. 13 
6.5. 
Medications ............................................................................................................................... 13 
6.6. 
Tumor Evaluations ..................................................................................................................... 14 
6.7. 
Off Study  Visit. .......................................................................................................................... 15 
6.8. 
Permitted medications .............................................................................................................. 15 
6.9. 
Prohibited medications .............................................................................................................. 15 
6.10. 
End of study treatment / Withdrawal procedures..................................................................... 16 
6.11. 
Replacement of patients. ........................................................................................................... 17 
6.12. 
Schedule of events ..................................................................................................................... 17 
7. 
Adverse Events .................................................................................................................... 18 
7.1. 
Definition of Dose-Limiting Toxicities (DLT) ............................................................................... 19 
7.2. 
Attribution of adverse events. ................................................................................................... 20 
7.3. 
Nivolumab.................................................................................................................................. 20 
7.4. 
Plinabulin ................................................................................................................................... 22 
8. 
Safety Parameters and Definitions: ...................................................................................... 23 
8.1. 
Adverse Events: .......................................................................................................................... 23 
8.2. 
Serious Adverse Events: ............................................................................................................. 23 
8.3. 
Data and Safety Monitoring Plan .............................................................................................. 24 
9. 
Statistical Methods and data analysis. .................................................................................. 24 
9.1. 
Sample size determination for the second phase of the study. ................................................. 24 
9.2. 
Efficacy Analysis. ........................................................................................................................ 24 
IRB Approved 
Document Release Date: 06/13/2018
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Printed on 12/7/2018

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9.3. 
Time to event definitions. .......................................................................................................... 25 
9.4. 
Analysis of other endpoints ....................................................................................................... 25 
   10.0 References. .......................................................................................................................... 26 
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