Study of Nivolumab in Combination With GM.CD40L Vaccine in Adenocarcinoma of the Lung

Study Overview
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Brief Summary
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The purpose of this study is to find out what effects (good and bad) a tumor vaccine (GM.CD40L) used in combination with Nivolumab will have on participants and their cancer. Another purpose of the study is to find out the maximum tolerated dose of nivolumab in combination with GM.CD40L vaccine. Investigators also want to find out if the combination of GM.CD40L and nivolumab can boost the immune system of participants like you, and how their immune system reacts, both before and after the treatment.

Detailed Description
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This study has two parts and participants may be involved in either Phase I part or Phase II. Phase I: Investigators plan to enroll participants in cohorts of 6 and monitor side effects over a 21 day period to determine the maximum tolerated dose (MTD) of nivolumab, which will be given in combination with GM.CD40L. This is being done since this study involves a combination of treatments that have not been studied in humans before and to find the best dose for the Phase II part of the study. Phase II: Investigators plan to compare any clinical benefit in the participants who receive the combination of GM.CD40L vaccine with nivolumab, to participants that receive only nivolumab.

Official Title
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A Randomized Phase I/II Study of Nivolumab in Combination With GM.CD40L Vaccine in Adenocarcinoma of the Lung

Conditions
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Lung Cancer, Adenocarcinoma of the Lung

Intervention / Treatment
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* Drug: Nivolumab
* Biological: GM.CD40L Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic diagnosis of advanced/metastatic adenocarcinoma of the lung Eastern Cooperative Oncology Group (ECOG) performance status of 0/1 Chemotherapy naïve or have completed adjuvant chemotherapy for non-small cell lung cancer (NSCLC) >6 months prior Adequate bone marrow, renal and hepatic function Must have measurable metastatic disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria Mandatory archival tissue or willingness to undergo a fresh biopsy Life expectancy of greater than 6 months Exclusion Criteria: Symptomatic brain metastasis or uncontrolled central nervous system (CNS) metastasis Pregnancy or breast feeding Serious uncontrolled medical disorder or active infection that would impair the participant's ability to receive study treatment Prior use of a PD1 or PDL1 inhibitor Concurrent use of other anticancer approved or investigational agents is not allowed Autoimmune disorders Prior malignancy in past 2 years Systemic steroids at doses greater than 10 mg/day of prednisone or the equivalent Any other pre-existing immunodeficiency condition (including known HIV infection)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I and Phase II Treatment Arm<br>Participants will receive nivolumab and GM.CD40L. Treatment will be administered on an outpatient basis. The nivolumab will be given first followed by the GM.CD40L vaccine for those enrolled on this arm. | Drug: Nivolumab<br>* Participants will receive treatment with nivolumab as a 60-minute +/-5 minutes intravenous (IV) infusion on Day 1 and 15 of each 28-day cycle.<br>* Other names: Anti-PD-1;Biological: GM.CD40L Vaccine<br>* GM.CD40L will be injected intradermally every 2 weeks for 4 injections, then every month for 4 injections, then every 3 months until the patient is off treatment.<br>* Other names: Cell Vaccine;|
| Active Comparator: Phase II Control Arm<br>Nivolumab treatment without GM.CD40L. Nivolumab will be given every 2 weeks at a dose of 3mg/kg. | Drug: Nivolumab<br>* Participants will receive treatment with nivolumab as a 60-minute +/-5 minutes intravenous (IV) infusion on Day 1 and 15 of each 28-day cycle.<br>* Other names: Anti-PD-1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Recommended Phase II Dose | The recommended Phase II dose will be defined as the highest dose level of GMCD40L vaccine in combination with nivolumab that induced dose limiting toxicity (DLT) in fewer than 33% of patients. | Up to 2 months | 
| Phase II: Objective Response Rate (ORR) | Objective tumor response per treatment arm. ORR: Complete Response (CR) = disappearance of all target lesions + Partial Response (PR) = 30% decrease in the sum of the longest diameter of target lesions. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II: Overall Survival (OS) | OS per treatment arm. Overall survival is defined as the time from randomization until death from any cause. | Up to 2 years | 
| Phase II: Progression-free Survival (PFS) | PFS per treatment arm. Progressive Disease (PD): = 20% increase in the sum of the longest diameter of target lesions. | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced, metastatic, lung disease, adenocarcinoma, non-small cell lung cancer (NSCLC)