Directly injecting biologics into lung cancer tumors might improve response rates beyond those achievable with systemic therapy alone, according to the research behind a new phase II clinical trial testing the approach.
The pioneering open label, multisite trial combines gene-mediated cytotoxic immunotherapy with standard of care for patients with refractory stage III/IV non-small cell lung cancer. The immunotherapy—two courses of aglatimagene besadenovec—is injected directly into an accessible tumor site under CT or ultrasound imaging.
Patients also receive 14 days of oral valacyclovir to heighten broader immune responses to the injectable biologic, which contains herpes simplex virus gene HSVtk.
The two-punch approach directly manipulates the tumor microenvironment while supporting systemic effects, explains principal investigator Daniel H. Sterman, MD, Thomas and Suzanne Murphy Professor of Pulmonary and Critical Care Medicine.
“When you give the patient valacyclovir, the drug in the tumor site is converted into a toxic metabolite that kills tumor cells and activates—together with HSVtk—a robust immune response. It acts not only locally where you do the injection, but anywhere in the body where tumor cells may be.”
“The drug in the tumor site is converted into a toxic metabolite that kills tumor cells and activates—together with HSVtk—a robust immune response.”Daniel H. Sterman, MD
The study is one of the first to deliver immunotherapy directly into patients’ lung tumors. Patients will be followed for three years following the investigational treatment. Researchers will assess tumor response rates, adverse events, immune cell responses, patient-reported symptoms, and survival rates.
A New Phase II Trial
The phase II trial will evaluate the safety and efficacy of adding gene mediated cytotoxic immunotherapy to standard of care in patients with stage III/IV non-small cell lung cancer that are not responding to a first line immune checkpoint inhibitor.
Directly Targeting Tumors
The study will determine whether delivering two rounds of the immunotherapy directly to tumor sites, via CT or ultrasound guided injection, is a safe approach that improves tumor response rates.
Anticipated Systemic Effects
A Long-Term Solution
Dr. Sterman and other interventional pulmonologists hypothesize that in the long-term, combining injectable biologics with available immune checkpoint inhibitors may provide a less invasive, safer, and more effective means of treating lung cancer.