NCT03004183

SBRT and Oncolytic Virus Therapy Before Pembrolizumab for Metastatic TNBC and NSCLC

Phase II Window of Opportunity Trial of Stereotactic Body Radiation Therapy and In Situ Oncolytic Virus Therapy in Metastatic Triple Negative Breast Cancer and Metastatic Non-Small Cell Lung Cancer Followed by Pembrolizumab

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 57 (actual)
• Sponsor: The Methodist Hospital Research Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase II trial to determine the efficacy and safety of stereotactic body radiation therapy (SBRT) and in situ oncolytic virus therapy used as a window of opportunity treatment before pembrolizumab in patients with metastatic triple negative breast cancer (TNBC) and metastatic non-small cell lung cancer (NSCLC). In situ oncolytic virus therapy will consist of adenovirus-mediated expression of herpes simplex virus thymidine kinase (ADV/HSV-tk) plus valacyclovir therapy.

Detailed description

This is a Phase II trial to determine the efficacy and safety of stereotactic body radiation therapy (SBRT) and in situ oncolytic virus therapy used as a window of opportunity treatment before pembrolizumab in patients with metastatic triple negative breast cancer (TNBC) and metastatic non-small cell lung cancer (NSCLC). In situ oncolytic virus therapy will consist of adenovirus-mediated expression of herpes simplex virus thymidine kinase (ADV/HSV-tk) plus valacyclovir. Male and female patients aged ≥ 18 years with histologically confirmed locally advanced or metastatic TNBC that has relapsed on or is refractory to 1 or more lines of standard of care therapy or histologically or cytologically confirmed metastatic NSCLC that is immunotherapy and chemotherapy naïve or previously treated with 1 cycle of platinum-containing chemotherapy are eligible to participate in the study. ADV/HSV-tk (5 x 1011 viral particles) in a 2-mL total volume will be injected intratumorally on Day 0 of the study. Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days. Valacyclovir treatment will be administered 24 hours after the gene vector injection from Day 1 to Day 15 of the study. SBRT of 30 gray (Gy; 6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16 of the study. Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 of the study and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. The primary endpoint will be the objective response rate of ADV/HSV-tk + valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC. RECIST 1.1 will be used to assess treatment response. Secondary endpoints will include a) clinical benefit rate; b) duration of response; c) overall survival and progression-free survival rates; d) toxicity (toxicity will be defined as any treatment-related death or any ≥ grade 3 toxicity excluding alopecia and constitutional symptoms as assessed by the NCI CTCAE v4.03); and e) antitumor activity of ADV/HSV-tk plus valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab.

Conditions

• Metastatic Non-small Cell Lung Cancer
• Metastatic Triple-negative Breast Cancer

Interventions

Type	Name	Description
BIOLOGICAL	ADV/HSV-tk	Replication-defective recombinant adenovirus vector
DRUG	Valacyclovir	Prodrug of the antiviral drug acyclovir
RADIATION	SBRT	Low-dose SBRT
DRUG	Pembrolizumab	Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody

Timeline

• Start date: 2017-07-01
• Primary completion: 2022-07-22
• Completion: 2024-01-09
• First posted: 2016-12-28
• Last updated: 2024-10-15
• Results posted: 2023-01-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study