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
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 5
Healthy volunteers: no

Brief summary:
This phase I/II trial studies the side effects and best dose of plinabulin when given together with nivolumab and to see how well they work in treating patients with stage IIIB-IV non-small cell lung cancer that has come back or spread to other places in the body. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as plinabulin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab and plinabulin together may work better at treating patients with non-small cell lung cancer.

Detailed description:
PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of the combination of nivolumab and plinabulin. (Phase I)

II. To determine the overall response rate (ORR) of treatment with nivolumab with the addition of plinabulin in the treatment of advanced stage non-small cell lung cancer in the second line setting. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the progression free survival (PFS), disease control rate (DCR), duration of response (DOR) and overall survival (OS) of patients treated with nivolumab in combination with plinabulin.

II. To determine the safety and tolerability of the combination of plinabulin and nivolumab.

TERTIARY OBJECTIVES:

I. Patients who have a pre-treatment and/or post cycle one biopsy will have flow cytometry of their tissue to identify infiltration of immune cells, rates of expression of programmed cell death 1 (PD-1), programmed cell death 2 (PD-2) and programmed cell death 1 ligand 1 (PDL1).

OUTLINE: This is a phase I, dose-escalation study of plinabulin followed by a phase II study.

Patients receive plinabulin intravenously (IV) over 30 minutes and nivolumab IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 28 days.

Arms:
arm 1: Patients receive plinabulin IV over 30 minutes and nivolumab IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Interventions: intervention 1: Nivolumab intervention 2: Plinabulin
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV

Protocol document:
Prot_SAP_000.pdf: 
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Page 1 of 27 
 
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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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9.3. 
Time to event definitions. .......................................................................................................... 25 
9.4. 
Analysis of other endpoints ....................................................................................................... 25 
   10.0 References. .......................................................................................................................... 26 
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