FDA Grants Fast Track Designation to Novel Pancreatic Cancer Drug

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The FDA granted Fast Track Designation to Candel Therapeutics, Inc’s aglatimagene besadenovec (CAN-2409) in combination with valacyclovir for the treatment of patients with pancreatic ductal adenocarcinoma (PDAC).¹ The novel off-the-shelf therapy is administered by a localized injection that is believed to provide a safety benefit compared with standard systemic administration in this patient population.

“We are pleased with the FDA's decision to grant fast track designation for CAN-2409 in pancreatic cancer,” said Paul Peter Tak, MD, PhD, FMedSci, president and chief executive officer of Candel Therapeutics, in a press release.¹ “This milestone follows our first interim data report from the randomized Phase II 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.”

Aglatimagene besadenovec is an adenoviral replication-defective engineered gene construct that encodes the herpes simplex virus (HSV)–derived thymidine kinase gene, which is transported into tumor cells at the injection site.²

HSV-thymidine kinase is subsequently expressed by tumor cells, which converts generic prodrugs into a toxic nucleotide analogue. Studies have indicated that cells exposed to the analogue undergo apoptosis. Meanwhile, the adenoviral serotype 5 capsid protein produces a proinflammatory signal that leads to a CD8+ T cell–mediated response.

A Phase II study (NCT02446093) is currently investigating neoadjuvant therapy with aglatimagene besadenovec plus valacyclovir with standard chemoradiation and surgery for the treatment of patients with borderline resectable or locally advanced nonmetastatic PDAC.³

Enrollment criteria includes administration of at least two months of standard-of-care (SOC) induction chemotherapy comprised of four cycles of FOLFIRINOX-based treatment or two cycles of gemcitabine/nab-paclitaxel (Abraxane).⁴ Patients randomly assigned to the investigational cohort in the open-label, Phase II trial (n = 10) were administered aglatimagene besadenovec and prodrug followed by chemoradiation with capecitabine, 5-fluorouracil, or gemcitabine and radiation for 3 to 5.5 weeks.

During chemoradiation, patients were administered aglatimagene besadenovec and prodrug before being restaged and going on to resection, where they were again administered aglatimagene besadenovec and prodrug. Patients randomly assigned to the control cohort (n = 9) were administered standard chemoradiation and surgery.

The trial’s primary endpoints include safety and resection rate, with secondary endpoints of overall survival (OS), progression-free survival, pathologic tumor response, CA 19.9, quality of life, and immune biomarkers.

As of the data cutoff date of August 21, 2023, aglatimagene besadenovec and prodrug plus SOC chemoradiation prior to surgery was found to produce an extended and sustained survival benefit among patients with borderline resectable PDAC (n= 13).⁵

The study showed an estimated 71.4% survival rate after both 24 and 36 months compared with 16.7% in the control cohort. Further, five of seven patients in the investigational cohort were alive at the time of cutoff compared with one patient in the control cohort. Median OS was not yet reached in the investigational cohort compared with 12.5 months in the control group.

Notably, the administration of aglatimagene besadenovec was found to produce robust immune activation with an acceptable safety profile, showing 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 said in the release.¹ “We are grateful to the patients, caregivers, investigators, and clinical sites that have taken part in this clinical trial.”

References

1. Candel Therapeutics receives FDA fast track designation for CAN-2409 in pancreatic cancer. News release. Candel Therapeutics, Inc. December 12, 2023. Accessed December 20, 2023. https://ir.candeltx.com/news-releases/news-release-details/candel-therapeutics-receives-fda-fast-track-designation-can-0
2. Platforms: CAN-2409. Candel Therapeutics, Inc. website. Accessed December 20, 2023. https://www.candeltx.com/platforms/
3. Neoadjuvant CAN-2409 in combination with chemoradiation or SBRT for borderline resectable pancreatic adenocarcinoma (PaTK02). ClinicalTrials.gov. Updated October 16, 2023. Accessed December 20, 2023. https://clinicaltrials.gov/study/NCT02446093
4. 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). Candel Therapeutics, Inc. website. Accessed December 20, 2023. https://www.candeltx.com/wp-content/uploads/news/PaTK02%20SITC%20Poster%20Final%2016OCT2023%20%281%29.pdf
5. 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 December 20, 2023. https://ir.candeltx.com/news-releases/news-release-details/candel-therapeutics-announces-initial-positive-interim-data#:~:text=Release%20Details-,Candel%20Therapeutics%20Announces%20Initial%20Positive%20Interim%20Data%20from%20Randomized%20Phase,in%20Non%2DMetastatic%20Pancreatic%20Cancer&text=In%20patients%20with%20progressive%20disease,not%20in%20the%20control%20arm.