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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer, Nonsmall Cell
• Intervention / Treatment: Other: Blood and tissue samples

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.

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

• Study Contact: Name: Alicia Patrick; Phone Number: (980) 292-1746; Email: Alicia.Patrick@atriumhealth.org

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute
      • Contact: Alicia Patrick; Phone Number: 980-292-1746; Email: alicia.patrick@atriumhealth.org
      • Principal Investigator: Kathryn Mileham, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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. These treatments are managed according to standard of care.

Description

Inclusion Criteria

1. 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.
2. Age greater than or equal to18 years at the time of consent.
3. 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.
4. Patients are allowed to continue maintenance chemotherapy.
5. Ability to understand and comply with study procedures for the entire length of the study.
6. Known PD-L1 prior to initiation of first-line treatment for NSCLC.

Exclusion Criteria

1. 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.
2. Patients whose tumors harbor known first line treatment druggable gene abnormalities (e.g. EGFR, BRAF, ALK, ROS1).
3. Patients who have ever received or are currently receiving other types of immunotherapies (nivolumab, ipilimumab, durvalumab or atezolizumab).
4. Known pregnancy.
5. Patients who progress per the enrolling investigator while on treatment with pembrolizumab prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Single Arm; 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; Blood and tissue will be collected to perform ctDNA and immune biomarkers assessment to predict progression within 6 months of pembrolizumab discontinuation.

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

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Kathryn Mileham, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2023
• Primary Completion (Estimated): September 1, 2035
• Study Completion (Estimated): September 1, 2035

Study Registration Dates

• First Submitted: December 6, 2021
• First Submitted That Met QC Criteria: June 8, 2022
• First Posted (Actual): June 13, 2022

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: LCI-LUN-IMM-BIO-001; 00058707 (Other Identifier: IRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No