On February 25, 2025 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, reported final overall survival data from the completed randomized controlled phase 2 clinical trial of CAN-2409 plus valacyclovir (prodrug), together with standard of care (SoC) chemoradiation, followed by resection, in patients with borderline resectable PDAC (Press release, Candel Therapeutics, FEB 25, 2025, View Source [SID1234650521]).

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Final data of the randomized controlled clinical trial, updated with an additional nine months of follow-up, confirmed a durable improvement in survival for patients treated with CAN-2409 plus SoC therapy (n=7) compared to SoC alone (n=6). Notably, long-term survivors in the CAN-2409 arm, remaining alive at 66.0, 63.6, and 35.8-months post-enrollment experienced disease recurrence but, in contrast to patients in the control arm with disease recurrence, responded to salvage chemotherapy and have experienced extended and ongoing post-progression survival at the time of the data cutoff (February 20, 2025), further highlighting the sustained benefit of CAN-2409 in this aggressive disease setting.

"Pancreatic cancer remains one of the most difficult to treat diseases," said W. Garrett Nichols, MD, MS, Candel’s Chief Medical Officer. "Patients with borderline resectable PDAC often have undetectable metastases that are not cleared with current standard of care neoadjuvant chemoradiation and surgery. CAN-2409 is a first-in-class multimodal immunotherapy candidate designed for in situ vaccination against the patient’s tumor, which offers the potential to control this disease and to prolong survival, thus improving outcomes following this dismal prognosis."

Data highlights:

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Prolonged and sustained survival was observed in this randomized controlled clinical trial after experimental treatment with CAN-2409 compared to the control group in patients with borderline resectable PDAC

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Estimated median overall survival after enrollment was 31.4 months in the CAN-2409 group (n=7) versus only 12.5 months in the control group (n=6).

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Median survival post-progression was 21.2 months in patients who received CAN-2409 compared to 7.2 months in the control arm.
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Importantly, three out of seven patients who received CAN-2409 were still alive at the time of data cut-off with a survival of 66.0, 63.6, and 35.8 months, respectively, after enrollment; survival from the time of diagnosis for these patients was 73.5, 68.8, and 41.3 months, respectively. Of these, the first patient had stage IV metastatic disease detected during surgery, the second had residual tumor present at the resection margin, and the third had adenocarcinoma with negative resection margins. In contrast, only one out of six patients randomized to SoC chemotherapy arm remained alive at the data cut-off (61.2 months from enrollment and 65.5 months from diagnosis); histologic analysis at resection showed intraepithelial neoplasia (without evidence of residual invasive adenocarcinoma) in this patient, which is associated with improved prognosis.

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Previous analysis at 24 months showed survival rates of 71.4% in patients treated with CAN-2409 compared to 16.7% in the control group.

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Previous analysis of blood and resected tumors showed consistent and robust activation of the immune response after experimental treatment with CAN-2409

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In pancreatic tissue of patients treated with CAN-2409 plus prodrug, together with SoC (but not SoC alone), dense aggregates of CD8+ granzyme B+ cytotoxic tumor infiltrating lymphocytes, dendritic cells, and B cells were observed in the tumor microenvironment.

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Increased levels of soluble granzymes B and H, along with pro-inflammatory cytokines, including IFN-γ, were detected in peripheral blood following CAN-2409 treatment, but not in the control arm, supporting CAN-2409’s ability to drive a potent systemic anti-tumoral immune response.

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CAN-2409 continued to be associated with a favorable safety/tolerability profile

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The addition of CAN-2409 regimen to SoC was generally well-tolerated, with no dose-limiting toxicities, including no cases of pancreatitis.

"The notable benefits observed with CAN-2409 in this clinical trial, including evidence of a long tail of survival, highlights the transformative potential of this biological multimodal immunotherapy in difficult to treat cancers", said Paul Peter Tak, MD, PhD, FMedSci, CEO and President of Candel. "Recently, the Company announced positive, statistically significant topline data for CAN-2409 based on a large, randomized, placebo-controlled clinical trial in localized prostate cancer. The data presented today support the potential of CAN-2409 across various solid tumors, by showing its potential to alter the balance between the pancreatic tumor and the anti-tumor immune response, even in patients with residual tumor, improving long-term survival in a subset of the patients. Based on these promising findings, the Company has decided to prepare for a larger, late-stage randomized controlled clinical trial of CAN-2409 in PDAC."

The FDA previously granted Fast Track Designation and Orphan Drug Designation to the Company for CAN-2409 in combination with valacyclovir for the treatment of patients with PDAC.

About CAN-2409

CAN-2409, Candel’s most advanced multimodal biological immunotherapy candidate, is an investigational, off-the-shelf, replication-defective adenovirus designed to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient’s specific tumor and induce an individualized, systemic immune response against the tumor. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. Together, this regimen is designed to induce an individualized and specific CD8+ T cell-mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity, based on in situ vaccination against a variety of tumor antigens. Because of its versatility, CAN-2409 has the potential to treat a broad range of solid tumors. Encouraging monotherapy activity, as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors, have previously been shown in several preclinical and clinical settings. More than 1,000 patients have been dosed with CAN-2409 with a favorable tolerability profile to date, supporting the potential for combination with other therapeutic strategies.

Currently, Candel is evaluating CAN-2409 in non-small cell lung cancer (NSCLC), PDAC, and localized, non-metastatic prostate cancer. In December 2024, Candel announced that CAN-2409 achieved its primary endpoint in a pivotal phase 3 clinical trial in men with intermediate-to-high-risk, localized prostate cancer, demonstrating statistically significant improvement in disease-free survival when added to SoC radiation therapy +/- androgen deprivation therapy. CAN-2409 plus prodrug has been granted Fast Track Designation by the FDA for the treatment of PDAC, stage III/IV NSCLC in patients who are resistant to first line PD-(L)1 inhibitor therapy and who do not have activating molecular driver mutations or have progressed on directed molecular therapy, and localized prostate cancer. The FDA has also granted Orphan Drug Designation to CAN-2409 for the treatment of PDAC. Candel’s pivotal phase 3 clinical trial in localized prostate cancer was conducted under a Special Protocol Assessment (SPA) agreed with the FDA.