Candel Therapeutics' (NASDAQ: CADL) Lead Candidate CAN-2409 Combats Lung, Pancreatic And Prostate Cancers With Fast Track Designation For Three Cancers

Immunotherapy has transformed the way cancer is treated, but just 20% to 40% of patients typically respond to FDA-approved immune checkpoint inhibitor (ICI) treatments. 

Poor ICI treatment response has been linked to the tumor's ability to disguise antigen presentation and generate an immunosuppressive microenvironment. In addition, most conventional immunotherapies are not designed to educate the patient's immune system on how to recognize a variety of tumor antigens and neoantigens.

Amid this landscape, a clinical-stage biopharmaceutical company has developed a new multimodal biological approach that leverages the ability of viral gene constructs to activate cancer-killing mechanisms, exposing multiple tumor antigens to the immune system, resulting in vaccination against the tumor while inhibiting the immunosuppressive tumor microenvironment. 

Candel Therapeutics, Inc. CADL is developing a product candidate that is being studied in lung, pancreatic and prostate cancers. Candel's most advanced viral immunotherapy candidate, CAN-2409, is an investigational off-the-shelf replication-defective adenovirus designed to induce an individualized, systemic immune response against the patient's own tumor. 

Part of the company's adenovirus platform, CAN-2409 is injected directly into the tumor or target tissue using a localized injection, akin to the standard approach for vaccination. 

CAN-2409’s adenoviral construct serves as a vector to transport the HSV-thymidine kinase gene into tumor cells at the site of injection. These tumor cells can then express HSV-thymidine kinase, which converts generic, FDA-approved anti-herpes drugs – such as ganciclovir, acyclovir and valacyclovir – into a toxic nucleotide analog that blocks DNA synthesis in dividing cells.

Cancer cells exposed to the toxic nucleotide analog in the tumor microenvironment have been observed to undergo immunogenic cell death. Simultaneously, the adenoviral serotype 5 capsid protein elicits a strong pro-inflammatory signal in the tumor microenvironment, creating the optimal conditions to induce a specific CD8+ T cell-mediated response against the injected tumor and uninjected distant metastases for broad and systemic anti-tumor activity.

CAN-2409 is currently being studied in an open-label, phase 2 clinical trial in non-small cell lung cancer (NSCLC) and in randomized, controlled, blinded phase 2b and phase 3 clinical trials in prostate cancer. The company has recently released very encouraging data for CAN-2409's ability to improve overall survival in non-metastatic pancreatic cancer, with topline overall survival data in non-small cell lung cancer planned for this quarter (Q2 2024) and results from the prostate clinical trials later this year (Q4 2024). 

When it comes to NSCLC, the company previously presented data from the phase 2 clinical trial in which patients received two administrations of CAN-2409 plus prodrug. Those patients demonstrated the following:

1) Increased infiltration of CD8+ cytotoxic T cells in the tumor microenvironment, systemic expansion of effector T cells and increased soluble granzyme B levels in peripheral blood; 

2) Favorable changes in the trajectory of tumor progression; 

3) Decreased tumor size of target lesions in most patients; and 

4) Reduced size of uninjected tumor lesions.

The CAN-2409 immunotherapy antitumor strategy aims to increase the number of long survivors beyond 10 to 13 months. 

As previous work has shown that progressive disease could be converted into stable disease in most patients with non-small cell lung cancer after CAN-2409 treatment, the hypothesis is that this will translate into improved survival.

When it comes to pancreatic cancer, the company reported notable improvements in patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC) after experimental treatment with CAN-2409. The estimated overall survival rate was 71.4% at 24 months in CAN-2409-treated patients versus only 16.7% in the control arm after chemoradiation. 

In 2023, CAN-2409 received Fast Track Designation for both non-small cell lung cancer and pancreatic cancer, a validation from the FDA on its potential. CAN-2409 plus valacyclovir in combination with continued PD-1/PD-L1 agents is being evaluated in an ongoing, open-label phase 2 clinical trial in patients with late-stage NSCLC and an inadequate response to anti-PD(L)-1 therapy. In 2024, CAN-2409 also received Orphan Drug Designation from the FDA for CAN-2409 in borderline resectable pancreatic cancer. 

In the upcoming year, Candel plans to announce data readouts for the following: 

1) Phase 2 topline overall survival (OS) data for CAN-2409 in NSCLC, expected in Q2 2024;

2) Phase 2 topline data for CAN-2409 in low-to-intermediate-risk, localized, non-metastatic prostate cancer, expected in Q4 2024;

3) Phase 3 topline data for CAN-2409 in localized intermediate/high-risk prostate cancer, expected in Q4 2024.

Featured photo by National Cancer Institute on Unsplash.

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