Candel Therapeutics Reports Prolonged Survival in Phase 2 Trial of CAN-2409 for Advanced NSCLC Non-Responsive to ICI at 2024 ASCO Meeting

In May 2024, Candel Therapeutics, Inc. released promising data on the efficacy of their experimental treatment, CAN-2409, in combination with valacyclovir, for patients with advanced non-small cell lung cancer (NSCLC) who had not responded adequately to immune checkpoint inhibitor (ICI) therapy. This phase 2 clinical trial aimed to determine if the combination could improve overall survival in this challenging patient group.

The trial's results were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting by Charu Aggarwal, MD, MPH, FASCO, from the University of Pennsylvania. The study involved patients with Stage III/IV NSCLC who had shown disease progression despite prior ICI treatment. The participants received two administrations of CAN-2409 plus valacyclovir, alongside continued ICI therapy. The median overall survival (mOS) for these patients was 20.6 months, significantly higher than the 11.6 months observed in similar patients treated with standard docetaxel-based chemotherapy in a 2022 study.

Key findings from the trial included improved survival rates in both PD-(L)1 positive and negative tumors, and a beneficial effect on both injected and non-injected tumors, known as the abscopal response. This indicates a systemic immune response. Additionally, the treatment led to increased levels of CD8+ cytotoxic and CD4+ memory T cells, and higher soluble granzyme B levels, correlating with prolonged survival.

The safety profile for CAN-2409 was also favorable. No dose-limiting toxicities or severe treatment-related adverse events were recorded. Most side effects were mild to moderate, with only three cases of grade 3 adverse events (one instance of fever, two of pneumonitis).

Dr. Aggarwal noted the importance of these findings, especially given the limited treatment options for advanced NSCLC patients who do not respond to ICI therapy. The data suggest that CAN-2409 could potentially reactivate patients' immune systems, providing a durable therapeutic response.

Candel Therapeutics’ CEO, Paul Peter Tak, MD, PhD, expressed optimism about the results, highlighting the potential of CAN-2409 to convert progressive cancers into stable diseases with survival benefits. This builds on previous positive outcomes from CAN-2409 in pancreatic cancer, reinforcing its promise across multiple solid tumor types.

CAN-2409 is a multimodal biological immunotherapy designed to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to tumors, which, with valacyclovir, creates a toxic metabolite that kills cancer cells and induces a systemic immune response. This approach aims to treat a broad range of solid tumors effectively.

The trial involved 46 patients, divided into two cohorts based on disease status at study entry: stable disease (5 patients) and progressive disease (41 patients). The demographic profile included a median age of 67 years, with a near-even split between male and female participants. PD-(L)1 expression levels varied, with many having less than 1% expression, indicating a difficult-to-treat population.

CAN-2409 has previously received FDA Fast Track Designation for both NSCLC and pancreatic cancer, and Orphan Drug Designation for pancreatic cancer. These designations facilitate the development and expedite the review of drugs to treat serious conditions with unmet medical needs.

In conclusion, the phase 2 trial results for CAN-2409 in combination with valacyclovir show significant promise for improving survival in advanced NSCLC patients who have exhausted other treatment options. The upcoming phase 3 trials and continued research will further clarify the full potential of CAN-2409 as a transformative treatment in oncology.