Immune Signature Analysis of Disease Progression in Post Immunotherapy Lung Cancer Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to examine the association between ctDNA/immune biomarkers and disease progression in patients who, at immunotherapy discontinuation, have completed at least 20 of an anticipated 24 months of pembrolizumab monotherapy or pembrolizumab-combination chemotherapy for mNSCLC.

Detailed Description
-----------------
This is a prospective, non-randomized, pilot study. The target population is adults ≥18 years of age with metastatic non-small cell lung cancer that at immunotherapy discontinuation, have completed at least 20 of an anticipated 24 months of planned doses of pembrolizumab in the first line setting. The study will be conducted at various LCI locations; external sites may be added in the future. Subjects will have blood for ctDNA and immune markers collected at baseline, and every 3 months for up to approximately 6 months. Blood will be collected at disease progression if it occurs prior to 6 months, ensuring that the collection occurs prior to start of subsequent anti-cancer therapy. We will also collect data from standard of care CT scans every 3 months for up to 6 months or until disease progression. In patients undergoing standard of care biopsies, a portion of tumor tissue will be obtained and tested for tumor mutations. Archived tumor tissue collected pre-immunotherapy (if available) will also be tested.

Official Title
-----------------
A Prospective Study Of Immune Signatures In Metastatic Non-Small Cell Lung Cancer (mNSCLC) Patients At Completion Of Pembrolizumab Either As Monotherapy Or In Combination With Chemotherapy In The First Line Setting

Conditions
-----------------
Lung Cancer, Nonsmall Cell

Intervention / Treatment
-----------------
* Other: Blood and tissue samples


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Informed consent and HIPAA authorization for release of personal health information signed by the subject. Note: Data from tumor samples, blood samples and radiographic scans prior to enrollment date may be used. Age greater than or equal to18 years at the time of consent. Patients with metastatic non-small cell lung carcinoma have completed first line who, at immunotherapy discontinuation, have completed at least 20 of an anticipated 24 months of pembrolizumab monotherapy or pembrolizumab combination chemotherapy in the first line setting. Patients are allowed to continue maintenance chemotherapy. Ability to understand and comply with study procedures for the entire length of the study. Known PD-L1 prior to initiation of first-line treatment for NSCLC. Exclusion Criteria Enrollment/collection of baseline sample earlier than 7 days prior to scheduled last dose of pembrolizumab or more than 30 days after last dose of pembrolizumab. Patients whose tumors harbor known first line treatment druggable gene abnormalities (e.g. EGFR, BRAF, ALK, ROS1). Patients who have ever received or are currently receiving other types of immunotherapies (nivolumab, ipilimumab, durvalumab or atezolizumab). Known pregnancy. Patients who progress per the enrolling investigator while on treatment with pembrolizumab prior to enrollment.

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

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

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

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

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Single Arm<br>Biomarkers and ctDNA data generated from patients with metastatic non-small cell lung carcinoma who have completed first line pembrolizumab monotherapy or pembrolizumab-platinum doublet combination therapy, and have, at immunotherapy discontinuation, completed at least 20 of an anticipated 24 months of pembrolizumab. | Other: Blood and tissue samples<br>* Blood and tissue will be collected to perform ctDNA and immune biomarkers assessment to predict progression within 6 months of pembrolizumab discontinuation.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease progression status for the purpose of assessing its correlation with ctDNA measured at 0 months after pembrolizumab treatment completion | Disease progression status determined by the treating investigator per standard care | 6 months after pembrolizumab treatment completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease progression status for the purpose of assessing its correlation with circulating effector T cell anergy at 0 months after pembrolizumab treatment completion | Disease progression status determined by the treating investigator per standard care | 6 months after pembrolizumab treatment completion | 
| Disease progression status for the purpose of assessing its correlation with the rate of effector to central memory T cell conversion at 0 months after pembrolizumab treatment completion | Disease progression status determined by the treating investigator per standard care | 6 months after pembrolizumab treatment completion | 
| Disease progression status for the purpose of assessing its correlation with clonal circulating T cell diversity at 0 months after pembrolizumab treatment completion | Disease progression status determined by the treating investigator per standard care | 6 months after pembrolizumab treatment completion |