NCT03825510

Immunotherapy SBRT Sensitization of the Programmed Death-1 (PD-1) Effect

A Prospective Trail of Immunotherapy and Stereotactic Body Radiotherapy (SBRT) for the Treatment of Metastatic Lung Cancer: SBRT Sensitization of the Programmed Death-1 (PD-1) Effect

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: Crozer-Keystone Health System · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine efficacy, safety of Stereotactic Body Radiotherapy (SBRT) in combination with immunotherapy in participants with metastatic non-small cell lung cancer (NSCLC) who are eligible for an immunotherapy agent.

Detailed description

Blockade of the PD-1/PD-L1 T-cell checkpoint pathway is an effective and well tolerated approach to stimulating the immune response which is a critical option in the treatment of metastatic NSCLC. However, progression free survival (PFS) is increased by only 2-4 months and median overall survival (OS) by 3-9 months. There is compelling evidence that PFS is increased up to 3 fold and OS by 2 fold in patients receiving a course of radiation therapy while on immunotherapy. Radiotherapy is known to induce immunogenic tumor cell death and upregulation of dendritic cells and antigen presentation leading to activation of cytotoxic T-Cells. Dramatic T-cell activation has been demonstrated where tumor regression occurs outside the radiation treatment field in a phenomenon termed the abscopal effect and is associated with high dose radiation delivered via SBRT. As such, SBRT activation of T-cells could be complementary to immunotherapy and enhance T-cell mediated killing via PD-L1 blockade which could lead to lasting and durable tumor response with improved progression free survival and overall survival.

Conditions

• Metastatic Nonsmall Cell Lung Cancer
• Non Small Cell Lung Cancer

Interventions

Type	Name	Description
RADIATION	Stereotactic Body Radiotherapy	All patients in this trial will be treated with fractionated Stereotactic body radiation therapy. SBRT will be delivered to \<=3 sites in 3-5 fractions followed by administration of the specified immunotherapy agent (Nivolumab or Pembrolizumab). This approach will take advantage of the transient increase in antigen availability, increased antigen presentation and upregulation of PD-1 by tumor cells following ablative radiation therapy.

Timeline

• Start date: 2017-04-28
• Primary completion: 2022-03-08
• Completion: 2022-03-08
• First posted: 2019-01-31
• Last updated: 2023-03-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study