Viral Immunotherapy Combo Improves Survival in Patients With NSCLC


Candel also recently received orphan drug designation for CAN-3110 for treating recurrent, high-grade glioma.

CAN-2409 in combination with valacyclovir and standard of care (SoC) immune checkpoint inhibitor (ICI) therapy improved survival in patients with Stage III/IV non-small cell lung cancer (NSCLC) whose disease was not adequately responding to anti-PD-L1 ICI therapy.1

Data from a phase 2 trial (NCT04495153) evaluating the combination were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31 to June 4, in Chicago, Illinois, by coprincipal investigator Charu Aggarwal, MD, MPH, FASCO, Leslye M. Heisler Associate Professor for Lung Cancer Excellence at the Perelman School of Medicine, University of Pennsylvania.

“Current therapeutic options for advanced NSCLC patients whose disease progresses despite ICI treatment are limited; they are characterized by poor tolerability and limited clinical benefit,” Aggarwal said in a statement.1 “The data reported today suggest that CAN-2409 can reactivate these patients’ exhausted immune systems, including those with low PD-(L)1 expression. This systemic anti-tumor immune response translated to a durable response; increased numbers of circulating cytotoxic and memory T cells were associated with subsequent prolonged survival. I look forward to the continued development of CAN-2409 in NSCLC as a promising approach in an area of unmet therapeutic need.”

Aggarwal presented data current as of April 2024 showing that treated patients with progressive disease despite ICI had a median overall survival (mOS) of 20.6 months after 2 administrations of CAN-2409 plus prodrug contrasting with 11.6 months in control patients with a similar population from a 2022 trial. Survival was improved regardless of PD-L1 positivity, and a beneficial effect was seen on both injected and uninjected tumors in over 70% of patients with metastatic disease and at least 1 uninjected tumor. Investigators also observed a significant increase in circulating CD8+, CD4+, central memory T cells, and increased soluble granzyme B levels in peripheral blood after the second injection of CAN-2409, associated with prolonged survival.1

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CAN-2409, an investigational, off-the-shelf, replication-defective adenovirus, is designed to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a specific tumor and induce an individualized, systemic immune response against the tumor by using HSV-tk to locally convert orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells.

“The results from our phase 2 trial in NSCLC continue to support the tremendous promise of CAN-2409 across multiple solid tumors. We are particularly encouraged by the overall survival observed in the patients whose disease had progressed despite receiving prior anti-PD-(L)1 treatment. Improved overall survival is, ultimately, what matters to patients and to the regulators,” Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer, Candel, added.1 “These results, together with our recently reported overall survival data in a randomized clinical trial in pancreatic cancer, add to the growing body of evidence supporting the notion that CAN-2409 treatment may convert progressive cancer into stable disease associated with survival benefit in advanced cancers with high unmet medical needs.”

Earlier in May, the FDA granted Orphan Drug Designation to another of Candel’s viral immunotherapy candidates, CAN-3110, for treating recurrent, high-grade glioma (hGG), including glioblastoma. The FDA previously granted the therapy fast track designation. CAN-3110 is currently being evaluated in a phase 1b trial (NCT03152318).2

“We are grateful to the FDA for recognizing the urgent need for new treatments in rHGG. Patients, and their families, affected by this disease, face immense challenges that the standard of care and conventional therapies have failed to adequately address. The early clinical data suggests that CAN-3110's unique dual mechanism of action, combining oncolysis and immune activation, has the potential to overcome these challenges for rHGG patients,” principal investigator E. Antonio Chiocca, MD, PhD, Chair, Department of Neurosurgery, Brigham and Women's Hospital, and Professor, Harvard Medical School, said in a statement.2

1. Candel Therapeutics Reports Prolonged Overall Survival in Phase 2 Clinical Trial of CAN-2409 for Advanced Non-Small Cell Lung Cancer (NSCLC) in Patients Non-Responsive to Immune Checkpoint Inhibitor (ICI) Treatment at 2024 ASCO Annual Meeting. News release. Candel Therapeutics. May 23, 2024.
2. FDA Grants Orphan Drug Designation for CAN-3110 for the Treatment of Recurrent High-Grade Glioma. News release. Candel Therapeutics. May 30, 2024.
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