FDA Grants FTD to CAN-2409 Combo for Pancreatic Ductal Adenocarcinoma

Investigators observed dense lymphocyte aggregates, tumor structure disruptions, and necrosis in patients who were treated with the CAN-2409 combination.

CAN-2409 in combination with prodrug (valacyclovir; Valtrex) has received fast track designation from the FDA as a treatment for those with pancreatic ductal adenocarcinoma (PDAC), according to a press release from Candel Therapeutics, Inc.¹

The fast track designation follows an interim data report from the phase 2 PaTK02 trial (NCT02446093) evaluating CAN-2409 plus prodrug and standard-of-care neoadjuvant chemoradiotherapy before resection in borderline resectable nonmetastatic PDAC, which investigators presented at the 2023 Society for Immunotherapy of Cancer (SITC) Annual Meeting. Among 13 evaluable patients with borderline resectable disease, the estimated overall survival (OS) rate was 71.4% at 24 and 36 months among those who received the experimental regimen compared with 16.7% at 24 and 36 months among patients who received chemoradiation alone.² The median OS in each respective arm was not reached and 12.5 months.

Investigators observed dense lymphocyte aggregates, tumor structure disruptions, and necrosis in patients who were treated with the CAN-2409 combination. Additionally, most adverse effects (AEs) and laboratory abnormalities were grade 1 or 2, and included nausea (40%), fatigue (40%), abdominal pain (20%), fever (20%), flu-like symptoms (20%), anorexia (20%), and dizziness (20%). One patient experienced a serious AE (SAE) of acute kidney injury that was potentially associated with prodrug, and another had a serious grade 1 fever that may have been related to CAN-2409. Overall, investigators concluded that treatment with the experimental combination did not correlate with significant systemic or local toxicity.

“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 at Candel, said in the 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 [with] real-world data on patients receiving radiotherapy treatment. Candel remains on track to release updated [OS] data from the interim analysis of this clinical trial in the second quarter of 2024.”

CAN-2409, an investigational off-the-shelf adenovirus, is designed to administer the herpes simplex virus thymidine kinase (HSV-tk) gene to a tumor, thereby prompting a systemic, CD8-positive T-cell–mediated immune response to the disease.¹ It is believed that CAN-2409 may be able to elicit activity across a variety of solid tumors when administered as monotherapy or in combination with standard radiation, surgery, chemotherapy, and immune checkpoint inhibitors.

After completing standard-of-care induction chemotherapy, patients in the phase 2 PaTK02 trial were randomly assigned to receive standard chemoradiotherapy plus CAN-2409 and prodrug (n = 10) or standard chemoradiation alone (n = 9) followed by resection.²

The trial’s primary end points were safety and resection rate. Secondary end points included OS, progression-free survival, pathologic tumor response, quality of life, and immune biomarkers.

“Given frequent recurrence and short survival with [standard-of-care] chemotherapy for non-metastatic PDAC, effective new treatment options are urgently needed,” Garrett Nichols, MD, MS, chief medical officer at Candel, said in a press release on data from the PaTK02 trial.³ “We are encouraged by the improved survival associated with CAN-2409 for the treatment of borderline resectable PDAC, demonstrated for the first time in a randomized clinical trial. CAN-2409 was generally well tolerated without significant additional local or systemic toxicity when added to [standard-of-care] chemoradiation.”

References

1. Candel Therapeutics receives FDA fast track designation for CAN-2409 in pancreatic cancer. News release. Candel Therapeutics, Inc. December 12, 2023. Accessed January 3, 2024. https://bit.ly/47ur4xi
2. Nichols G, Bloomston M, Huitzil D, et al. Neoadjuvant CAN-2409 + prodrug plus chemoradiation for borderline resectable or locally advanced non-metastatic pancreatic adenocarcinoma (PDAC). Presented at the 2023 Society for Immunotherapy of Cancer (SITC) Annual Meeting; November 1-5, 2023; San Diego, CA; abstract 653.
3. Candel Therapeutics announces initial positive interim data from randomized phase 2 clinical trial of CAN-2409 in non-metastatic pancreatic cancer. News release. Candel Therapeutics, Inc. November 3, 2023. Accessed January 3, 2024. https://bit.ly/48GuvBK