FDA Grants Fast Track Status to Aglatimagene Besadenovec Plus Valacyclovir for Pancreatic Cancer

January 2, 2024

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The FDA has granted fast track designation to aglatimagene besadenovec plus valacyclovir for use as a potential therapeutic option in patients with pancreatic ductal adenocarcinoma.

Paul Peter Tak, MD, PhD, FMedSci

The FDA has granted fast track designation to aglatimagene besadenovec (CAN-2409) plus valacyclovir for use as a potential therapeutic option in patients with pancreatic ductal adenocarcinoma (PDAC), according to an announcement from Candel Therapeutics, Inc.¹

The adenoviral replication-defective engineered gene construct encodes the herpes simplex virus (HSV)–derived thymidine kinase gene.² The off-the-shelf therapy is administered via localized injection, which is hypothesized to have safety benefits over standard systemic administration.

The adenoviral construct transports the HSV-thymidine kinase gene into tumor cells at the injection site, according to the company. The tumor cells are then able to express HSV-thymidine kinase, which converts generic prodrugs like valacyclovir into a toxic nucleotide analogue. Cells with exposure to the analogue have been found to undergo cell death. Concurrently, the adenoviral serotype 5 capsid protein induces a proinflammatory signal that allows for CD8+ T cell–mediated response.

Neoadjuvant treatment with CAN-2409 plus valacyclovir with standard chemoradiation and surgery is under investigation in patients with borderline resectable or locally advanced nonmetastatic PDAC as part of a phase 2 study (NCT02446093).³

“We are pleased with the FDA's decision to grant fast track designation for CAN-2409 in pancreatic cancer,” Paul Peter Tak, MD, PhD, FMedSci, president and chief executive officer of Candel Therapeutics, Inc., stated in a press release.¹ “This milestone follows our first interim data report from the randomized phase 2 clinical trial in patients with borderline resectable PDAC that showed prolonged and sustained survival after experimental treatment with CAN-2409, especially when compared to real-world data on patients receiving radiotherapy treatment.”

Prior to enrollment, patients received at least 2 months of standard-of-care (SOC) induction chemotherapy, which consisted of 4 cycles of FOLFIRINOX-based or 2 cycles of gemcitabine/nab-paclitaxel (Abraxane).⁴ Those enrolled to the open-label, phase 2 study who were randomly assigned to the test arm (n = 10) received CAN-2409 and prodrug followed by chemoradiation with capecitabine, 5-fluorouracil, or gemcitabine and radiation over 3 to 5.5 weeks. During chemoradiation, they received CAN-2409 and prodrug again. They then were restaged and went on to resection, where they again received CAN-2409 and prodrug. Those in the control arm (n = 9) just received standard chemoradiation and surgery.

The primary end points of the trial include safety and resection rate. Secondary end points include overall survival, progression-free survival, pathologic tumor response, CA 19.9, quality of life, and immune biomarkers.

At the time of the data cutoff date of August 21, 2023, it was found that CAN-2409 and prodrug plus SOC chemoradiation prior to surgery resulted in extended and sustained survival in patients with borderline resectable PDAC (n= 13).⁵ Data indicated the estimated 24- and 36-month survival rates were both 71.4% in the test arm vs 16.7% in the control arm. Notably, 5 out of 7 patients in the test arm were alive at the time of cutoff vs only 1 patient in the control arm. In the CAN-2409 arm, the median OS was not yet reached vs 12.5 months in the control arm.

Moreover, it was found that after receipt of CA-2409, robust immune activation was observed. The therapy also had an acceptable tolerability profile, with no dose-limiting toxicities and no cases of pancreatitis.

“Candel remains on track to release updated OS data from the interim analysis of this clinical trial in the second quarter of 2024,” Tak added in the press release.¹ “We are grateful to the patients, caregivers, investigators, and clinical sites that have taken part in this clinical trial.”