Dr Aggarwal on the Rationale For Evaluating CAN-2409 in NSCLC

Charu Aggarwal, MD, MPH, FASCO, physician leader, Airways Malignancies Research, director, Precision Oncology Innovation, Penn Center for Cancer Care Innovation, section chief, Head & Neck and Thoracic Cancers, Hematology-Oncology, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, discusses the rationale for evaulating the combination of CAN-2409, valacyclovir (Valtrex), and continued standard-of-care immune checkpoint inhibitors in patients with stage III/IV non–small cell lung cancer (NSCLC) who have had an inadequate response or were refractory or resistant to anti–PD-1 or –PD-L1 therapy. Notably, this combination was studied in a phase 2 trial (NCT04495153), findings from which were presented at the 2024 ASCO Annual Meeting.

This trial was designed in response to a significant unmet clinical need, Aggarwal begins. Althoughimmunotherapy has revolutionized the treatment of patients with advanced- and early-stage lung cancer, there remains a subset of patients who either do not respond adequately to or experience progression shortly after receiving immuno-chemotherapy, according to Aggarwal. In these cases, treatment options are limited, she says. The goal of this phase 2 trial is to introduce an agent that can either rejuvenate the immune response or resensitize the immune system to effectively target cancer cells.

CAN-2409 employs a viral approach, where the therapy is locally administered directly into the tumor. When combined with valacyclovir, an oral prodrug, the viral particles are broken down and release pro-inflammatory elements, she reports. This process induces CD8-positive cytotoxic cells and generates a local immunization that triggers systemic T-cell responses against both the treated tumor and distant, untreated metastases, Aggarwal adds.

Extensive clinical trial work has been conducted with this combination, including in patients with mesothelioma and advanced NSCLC, where the therapy is delivered into the pleural space, directly into tumors, and early into lymph nodes, she expands. In this trial, investigators focused on injecting CAN-2409 intratumorally in patients with advanced lung cancer to explore its potential in reinvigorating the immune system and enhancing its ability to combat the disease, Aggarwal concludes.