CCL21-Gene Modified Dendritic Cell Vaccine and Pembrolizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer

Stage IV Lung Cancer AJCC v8 Clinical Trial

Official title: A Phase I Trial of Intratumoral Administration of CCL21-Gene Modified Dendritic Cell (Ad-CCL21-DC) Combined With Intravenous Pembrolizumab for Advanced NSCLC

Status Active, not recruiting

Clinical Trial Summary

This phase I trial studies the side effects and best dose of autologous dendritic cell-adenovirus CCL21 vaccine (CCL21-gene modified dendritic cell vaccine) combined with intravenous pembrolizumab, and to see how well they work in treating patients with stage IV non-small cell lung cancer. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving CCL21-gene modified dendritic cell vaccine with pembrolizumab may work better in treating patients with stage IV non-small cell lung cancer.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Dose escalation: To determine the safety and maximum tolerated dose (MTD) of intratumoral injection of autologous dendritic cell-adenovirus CCL21 vaccine (CCL21 gene-modified DC [Ad-CCL21-DC]) when combined with intravenous pembrolizumab in 1) patients with advanced non-small cell lung cancer (NSCLC) without a sensitizing epidermal growth factor receptor (EGFR) mutation and/or anaplastic lymphoma kinase (ALK) gene rearrangement who have received prior systemic anti-cancer therapy for advanced disease that includes a PD -1 and/or PD-L1 inhibitor or 2) patients who have sensitizing EGFR mutations and/or ALK gene rearrangements and have received prior tyrosine kinase inhibitor therapy.

II. Dose expansion: To evaluate the objective response rate (ORR) in subjects treated with the dose established during dose escalation (ExD) of intratumoral injection of Ad-CCL21-DC when administered with intravenous pembrolizumab in 1) patients with advanced non-small cell lung cancer (NSCLC) without a sensitizing epidermal growth factor receptor (EGFR) mutation and/or anaplastic lymphoma kinase (ALK) gene rearrangement who have received prior systemic anti-cancer therapy for advanced disease that includes a PD -1 and/or PD-L1 inhibitor or 2) patients who have sensitizing EGFR mutations and/or ALK gene rearrangements and have received prior tyrosine kinase inhibitor therapy.

SECONDARY OBJECTIVES:

I. To define the adverse event (AE) profile of intratumoral injection of Ad-CCL21-DC (determined during dose escalation) when administered with intravenous pembrolizumab in 1) patients with advanced non-small cell lung cancer (NSCLC) without a sensitizing epidermal growth factor receptor (EGFR) mutation and/or anaplastic lymphoma kinase (ALK) gene rearrangement who have received prior systemic anti-cancer therapy for advanced disease that includes a PD -1 and/or PD-L1 inhibitor or 2) patients who have sensitizing EGFR mutations and/or ALK gene rearrangements and have received prior tyrosine kinase inhibitor therapy.

II. To determine drug target activity by analyzing serial pre- and post-treatment biopsies and blood specimens of intratumoral injection of Ad-CCL21-DC (determined during dose escalation) when administered with intravenous pembrolizumab in 1) patients with advanced non-small cell lung cancer (NSCLC) without a sensitizing epidermal growth factor receptor (EGFR) mutation and/or anaplastic lymphoma kinase (ALK) gene rearrangement who have received prior systemic anti-cancer therapy for advanced disease that includes a PD -1 and/or PD-L1 inhibitor or 2) patients who have sensitizing EGFR mutations and/or ALK gene rearrangements and have received prior tyrosine kinase inhibitor therapy.

OUTLINE: This is a dose-escalation study of autologous dendritic cell-adenovirus CCL21 vaccine.

Patients receive pembrolizumab intravenously (IV) over 30 minutes followed by autologous dendritic cell-adenovirus CCL21 vaccine by computed tomography (CT)-guided or bronchoscopic intratumoral (IT) injection on days 0, 21, and 42. Patients then receive pembrolizumab every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at day 63 and every 3 months thereafter. ;

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Lung Non-Small Cell Carcinoma
• Stage IV Lung Cancer AJCC v8
• Stage IVA Lung Cancer AJCC v8
• Stage IVB Lung Cancer AJCC v8

• NCT number: NCT03546361
• Study type: Interventional
• Source: Jonsson Comprehensive Cancer Center
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: July 8, 2019
• Completion date: January 11, 2025