Phase 2 Study of Glesatinib, Sitravatinib or Mocetinostat in Combination With Nivolumab in Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
The study will evaluate the clinical activity of nivolumab in combination with 3 separate investigational agents, glesatinib, sitravatinib, or mocetinostat.

Detailed Description
-----------------
Glesatinib is an orally administered multi-targeted tyrosine kinase inhibitor (TKI) that primarily targets the Axl and Mesenchymal-Epithelial Transition (MET) receptors. Sitravatinib is an orally-available, potent small molecule inhibitor of a closely related spectrum of receptor tyrosine kinases (RTKs) including MET, Axl, MERTK, VEGFR family, PDGFR family, KIT, FLT3, Trk family, RET, DDR2 and selected Eph family members. Mocetinostat is an orally administered histone deacetylase (HDAC) inhibitor. Nivolumab is a human IgG monoclonal antibody that binds to the programmed cell death-1(PD-1) receptor and blocks its interaction with programmed cell death ligand-1 (PD-L1) and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response including anti-tumor immune response. Combining an immunotherapeutic PD-L1 checkpoint inhibitor with an agent that has both immune modulatory and antitumor properties could enhance the antitumor efficacy observed with either agent alone. The study will begin with a lead-in dose escalation evaluation of two dose levels of each investigational agent in combination with nivolumab. Following completion of the lead-in dose escalation, enrollment into the Phase 2 study will proceed.

Official Title
-----------------
A Parallel Phase 2 Study of Glesatinib, Sitravatinib or Mocetinostat in Combination With Nivolumab in Advanced or Metastatic Non-Small Cell Lung Cancer

Conditions
-----------------
Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
-----------------
* Drug: Glesatinib
* Drug: Sitravatinib
* Drug: Mocetinostat
* Drug: Nivolumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of non-small cell lung cancer. Prior treatment with a checkpoint inhibitor (as appropriate per cohort) Adequate bone marrow and organ function Exclusion Criteria: Uncontrolled tumor in the brain Unacceptable toxicity with prior checkpoint inhibitor Impaired heart function

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glesatinib and Nivolumab<br>Glesatinib oral tablet administered twice daily in combination with Nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week | Drug: Glesatinib<br>* Glesatinib is a small molecule multi-targeted receptor tyrosine kinase inhibitor<br>* Other names: MGCD265;Drug: Nivolumab<br>* nivolumab is a programmed death receptor-1 (PD-1) blocking antibody<br>* Other names: Opdivo;|
| Experimental: Sitravatinib and Nivolumab<br>Sitravatinib oral capsule administered daily in combination with nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week | Drug: Sitravatinib<br>* Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases.<br>* Other names: MGCD516;Drug: Nivolumab<br>* nivolumab is a programmed death receptor-1 (PD-1) blocking antibody<br>* Other names: Opdivo;|
| Experimental: Mocetinostat and Nivolumab<br>Mocetinostat oral capsule administered three times weekly in combination with nivolumab administered as 240 mg IV every 2 weeks or 480 mg IV every 4 week | Drug: Mocetinostat<br>* Mocetinostat is an HDAC inhibitor.<br>* Other names: MGCD01013;Drug: Nivolumab<br>* nivolumab is a programmed death receptor-1 (PD-1) blocking antibody<br>* Other names: Opdivo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients experiencing tumor size reduction |  | Approximately 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients experiencing adverse events |  | up to 12 months | 
| Blood plasma concentration of the investigational agent |  | Up to 20 weeks | 
| Overall Survival |  | Up to 24 months | 
| Progression free survival |  | Up to 12 months |