CAN-2409 Shows Strong OS Outcomes in ICI-Refractory NSCLC

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Patients with advanced non–small cell lung cancer (NSCLC) who inadequately responded to immune checkpoint inhibitor (ICI) therapy had a median overall survival (mOS) of 24.5 months after receiving 2 courses of CAN-2409 (n = 46), according to final survival data from the phase 2a LuTK02 trial (NCT04495153).¹

A subset of 41 patients in this cohort who presented with progressive disease at baseline despite prior ICI treatment had an mOS of 21.5 months. This survival outcome was nearly double the typical mOS ranging from 9.8 to 11.8 months with standard-of-care docetaxel chemotherapy observed in similar refractory populations.

The extended follow-up, with a median follow-up time of 32.4 months for the per-protocol population, also showed the durability of the observed survival benefit. A total of 37% of patients with progressive disease post-ICI treatment remained alive at the 24-month mark.

“Treatment options are quite limited for patients with unresectable NSCLC who progress on anti-PD-1 therapy,” said Charu Aggarwal, MD, MPH, Leslye Heisler professor for Lung Cancer Excellence at the University of Pennsylvania’s Perelman School of Medicine and principal investigator of the study, in a press release. “The survival benefit seen in this study is striking, especially when compared to both the current standard of care treatment of docetaxel chemotherapy and other therapies under investigation for this patient group.”

Background and Trial Design

CAN-2409 is an investigational viral immunotherapy designed to induce in situ tumor antigen release and immune activation. The agent was evaluated in a phase 2a trial that enrolled stage III/IV patients with NSCLC who were refractory to ICIs (n = 33).²

Among 76 enrolled patients, 46 completed 2 courses of CAN-2409 with prodrug, either valacyclovir (Valtrex) or acyclovir (Sitavig), and comprised the per-protocol population. Pretreatment dropout rates aligned with expectations for advanced NSCLC trials.

Patients aged 18 years or older with stage III/IV NSCLC who were on first-line treatment with an anti–PD-1/anti–PD-L1 immune checkpoint inhibitor with or without chemotherapy were eligible for enrollment in the study. Enrollment was open to patients with evaluable disease per RECIST, an ECOG performance status of 0 or 1, and a willingness to undergo pre-treatment and on-treatment biopsies were among the inclusion criteria. Further, patients must not have been receiving focal therapy at more than 3 different sites within 12 months of enrollment and must have had no change of immune checkpoint inhibitor therapy within 6 months of enrollment.

The primary end points of the study include the response rate at 12 months and safety. Secondary end points are OS, progression-free survival, changes in patient-reported symptoms, and biomarker studies.

Additional Findings

A statistically significant improved OS was observed in nonsquamous NSCLC vs squamous NSCLC after experimental treatment with CAN-2409.¹ The mOS was 25.4 months per protocol population of patients with nonsquamous NSCLC with progressive disease at baseline despite ICI.

Nonsquamous histology correlated with improved survival. Fourteen of the 15 patients surviving more than 24 months and all 9 patients surviving more than 30 months had nonsquamous tumors. Immunologic profiling showed greater T-cell, B-cell, and dendritic cell activation in nonsquamous versus squamous subtypes.

An abscopal effect was observed in 69% of evaluable patients (n = 35), with shrinkage of uninjected lesions.

Safety remained favorable, with no new tolerability concerns during extended follow-up.

“The extension of survival in patients with nonsquamous disease is notable even when compared to data that have been reported for other investigational products, such as antibody-drug conjugates, for this patient population,” said W. Garrett Nichols, MD, chief medical officer of Candel, in the press release.¹ “CAN-2409, in addition to continued ICI treatment, may prolong survival beyond that offered by docetaxel chemotherapy and has the potential to be better tolerated.”

References

1. Candel Therapeutics reports both prolonged median overall survival and long tail of survival in phase 2a clinical trial of CAN-2409 in advanced non-small cell lung cancer (NSCLC) patients non-responsive to immune checkpoint inhibitor (ICI) treatment. News release. Candel Therapeutics, Inc. March 26, 2025. Accessed March 28, 2025. https://tinyurl.com/4b4xpd8v

2. CAN-2409 plus prodrug with standard of care immune checkpoint inhibitor for stage III/​IV NSCLC. ClinicalTrials.gov. Updated December 7, 2023. Accessed March 28, 2025. https://tinyurl.com/3djbkwkw