Positive Phase 2 Trial Results for CAN-2409 in Non-Metastatic Pancreatic Cancer

Candel Therapeutics, a biopharmaceutical firm, has reported promising interim results from its phase 2 clinical trial of CAN-2409, an immunotherapy treatment for borderline resectable pancreatic ductal adenocarcinoma (PDAC). The experimental treatment, when combined with valacyclovir and standard chemoradiation, demonstrated a significant enhancement in median overall survival, extending it to 28.8 months compared to the 12.5 months observed in the control group. This improvement was also reflected in the 24-month survival rate, which stood at 71.4% for patients treated with CAN-2409, significantly higher than the 16.7% rate in the control group.

The study, which included a data cut-off on March 29, 2024, revealed that four out of seven patients treated with CAN-2409 were still alive, with two surpassing the 50-month survival mark post-enrollment. In contrast, only one out of six patients in the control group survived beyond the data cut-off point. The treatment was well-tolerated, with no new safety concerns, dose-limiting toxicities, or cases of pancreatitis reported.

Analysis of resected tumors indicated a dense presence of immune cells, such as CD8+ cytotoxic tumor infiltrating lymphocytes and dendritic cells, suggesting that CAN-2409 effectively activated a robust antitumor immune response. The treatment also showed an increase in pro-inflammatory cytokines and soluble granzymes in the blood, further supporting its immune-activating properties.

Candel's Chief Medical Officer, Garrett Nichols, emphasized the urgent need for new treatment options due to the frequent recurrence and short survival rates associated with standard chemotherapy for non-metastatic PDAC. He expressed optimism regarding the durable survival improvements provided by CAN-2409, which was well-tolerated without significant additional toxicity.

The company's President and CEO, Paul Peter Tak, highlighted the failure of conventional immunotherapies in pancreatic cancer treatment, attributing this to the immunosuppressive tumor microenvironment. However, CAN-2409's ability to induce immunological changes in both pancreatic tissue and peripheral blood suggests a potential to alter the balance between the tumor and the patient's immune response, offering a path to improved survival.

Candel Therapeutics is a clinical-stage company developing multimodal biological immunotherapies to elicit a systemic anti-tumor immune response. CAN-2409, the lead candidate from their adenovirus platform, is currently in clinical trials for various cancers, including non-small cell lung cancer and prostate cancer. The company's enLIGHTEN™ Discovery Platform is also creating new viral immunotherapies for solid tumors.

Pancreatic cancer remains a significant health concern, being the fourth leading cause of cancer-related deaths in the United States. The disease has a high mortality rate, with PDAC accounting for 90% of all pancreatic carcinomas. Surgical resection is the only curative option, and the use of neoadjuvant chemotherapy and chemoradiation aims to increase the number of patients eligible for surgery. However, disease recurrence is common due to micrometastatic disease. The median overall survival for borderline resectable PDAC patients treated with neoadjuvant FOLFIRINOX with or without radiotherapy is only 22.2 months.

The immunosuppressive nature of PDAC has made immunotherapy with PD-1 antibodies unsuccessful, but CAN-2409's approach offers a new avenue for treatment. Candel is currently evaluating CAN-2409's effects in ongoing clinical trials for NSCLC, PDAC, and prostate cancer, with the FDA granting Fast Track Designation for its use in PDAC and NSCLC patients resistant to first-line PD-(L)1 inhibitor therapy.