CAN-2409/Valacyclovir Plus SOC Demonstrates Positive Survival in PDAC

The CAN-2409 combination improved survival post-progression vs standard-of-care therapy alone in the phase 2 PaTK02 trial.

Final overall survival (OS) data from the phase 2 PaTK02 trial (NCT02446093) were positive for CAN-2409 plus valacyclovir (Valtrex) with standard-of-care chemoradiation then resection in the treatment of a small cohort of patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC), according to a press release from the developer, Candel Therapeutics.¹

At the data cutoff of February 20, 2025, with an additional 9 months of follow-up, the trial combination achieved an estimated median OS of 31.4 months compared with 12.5 months in patients who received standard of care alone; median survival post-progression was 21.2 months with the treatment combination vs 7.2 months with standard of care. Additionally, of the 7 patients to receive the CAN-2409 treatment, 3 were still alive at the time of data cutoff with respective survivals of 66.0, 63.6, and 35.8 months after enrollment and 73.5, 68.8, and 41.3 months after diagnosis.

The prior analysis at 24 months highlighted a 71.4% survival rate with CAN-2409 vs 16.7% without.

Previously, CAN-2409 with valacyclovir was granted fast track designation and orphan drug designation.²

“The notable benefits observed with CAN-2409 in this clinical trial, including evidence of a long tail of survival, highlights the transformative potential of this biological multimodal immunotherapy in difficult-to-treat cancers,” Paul Peter Tak, MD, PhD, FMedSci, chief executive officer and president of Candel, stated.¹ “The data presented today support the potential of CAN-2409 across various solid tumors, by showing its potential to alter the balance between the pancreatic tumor and the anti-tumor immune response, even in patients with residual tumor, improving long-term survival in a subset of the patients. Based on these promising findings, the company has decided to prepare for a larger, late-stage randomized controlled clinical trial of CAN-2409 in PDAC.”

The open-label phase 2 PaTK02 trial evaluated the preliminary efficacy, immune biologic activity, and safety of CAN-2409 plus valacyclovir in patients with borderline resectable pancreatic cancer undergoing treatment with neoadjuvant chemoradiation or stereotactic body radiation therapy compared with standard of care.³

Patients 18 years or older were randomly assigned, in a 1:1 ratio, to receive either 2 to 3 courses of CAN-2409 plus valacyclovir and chemoradiation then resection (n = 7) or chemoradiation then resection alone (n = 6).

Eligibility criteria included pathologic diagnosis of PDAC treated with induction chemotherapy for at least 4 months, adequate health to undergo major surgery, tumor accessible for injection, an ECOG performance status of 0 or 1, and adequate organ function.

Those with primary hepatic dysfunction such as cirrhosis or active hepatitis, evidence of clinically significant pancreatitis determined by the investigator, evidence of significant ascites, other current malignancies, and other serious comorbid illnesses were among grounds for exclusion.

Primary trial end points were safety and 24-month OS. Key secondary end points included OS, progression-free survival, resection rate, disease-free survival, and biomarkers in tumor and peripheral blood.

In prior analyses of the tumor microenvironment, dense aggregates of CD8-positive granzyme B-positive cytotoxic tumor infiltrating lymphocytes, dendritic cells, and B cells were observed in patients who received CAN-2409 plus valacyclovir and standard of care. Also, increased levels of soluble granzymes B and H and pro-inflammatory cytokines were detected in peripheral blood after treatment with CAN-2409. These changes were not observed in the control arm.

Regarding safety, the tolerability profile of the CAN-2409 combination was favorable and showed no dose-limiting toxicities or cases of pancreatitis, which further supported previously known data.

References

1. Candel Therapeutics announces positive final survival data from randomized controlled phase 2 clinical trial of CAN-2409 in non-metastatic pancreatic cancer. News release. Candel Therapeutics, Inc. February 25, 2025. Accessed February 27, 2025. https://tinyurl.com/2tutnnf6
2. Candel Therapeutics receives FDA fast track designation for CAN-2409 in pancreatic cancer. News release. Candel Therapeutics, Inc. December 12, 2023. Accessed February 27, 2025. https://bit.ly/47ur4xi
3. Neoadjuvant CAN-2409 in combination with chemoradiation or SBRT for borderline resectable pancreatic adenocarcinoma (PaTK02). ClinicalTrials.gov. Updated January 8, 2024. Accessed February 27, 2025. https://tinyurl.com/mtjfa9dv