Candel Therapeutics Announces Positive Final Survival Data from Randomized Controlled Phase 2 Clinical Trial of CAN-2409 in Non-Metastatic Pancreatic Cancer

Rhea-AI Summary

Candel Therapeutics (NASDAQ: CADL) has announced positive final survival data from its Phase 2 clinical trial of CAN-2409 in non-metastatic pancreatic cancer. The randomized controlled study showed a remarkable improvement in estimated median overall survival - 31.4 months in the CAN-2409 treatment group versus only 12.5 months in the control group for patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC).

Notably, three of seven patients treated with CAN-2409 were still alive at 66.0, 63.6, and 35.8 months after enrollment, with survival from diagnosis reaching 73.5, 68.8, and 41.3 months respectively. This survival duration significantly exceeds expectations for standard pancreatic cancer treatment.

CAN-2409, a first-in-class multimodal immunotherapy designed for in situ vaccination against the patient's tumor, demonstrated a favorable safety profile and has previously received both Fast Track Designation and Orphan Drug Designation from the FDA for PDAC treatment. Based on these promising results, Candel plans to prepare for a larger, late-stage randomized controlled clinical trial of CAN-2409 in PDAC.

Positive

• Estimated median overall survival improved to 31.4 months with CAN-2409 vs. 12.5 months in control group
• Three of seven CAN-2409-treated patients still alive with survival of 66.0, 63.6, and 35.8 months after enrollment
• Median survival post-progression was 21.2 months with CAN-2409 compared to 7.2 months in control arm
• CAN-2409 previously received FDA Fast Track Designation and Orphan Drug Designation for PDAC treatment
• Favorable safety/tolerability profile with no dose-limiting toxicities

Negative

• sample size with only 7 patients in treatment group and 6 in control group

Insights

Oncology Clinical Trial Analyst

Candel Therapeutics' final Phase 2 data for CAN-2409 in pancreatic cancer represents a potential breakthrough in one of oncology's most challenging indications. The reported 31.4-month median overall survival versus 12.5 months in the control arm signifies a 151% improvement – remarkable in a disease where survival improvements are typically measured in weeks, not years.

The most compelling aspect is the long tail of survival, with three of seven CAN-2409-treated patients still alive at 66.0, 63.6, and 35.8 months post-enrollment. This suggests CAN-2409 may fundamentally alter disease trajectory in a subset of patients, creating durable responses that extend well beyond typical survival expectations for PDAC.

Particularly noteworthy is the 21.2-month post-progression survival in the treatment arm versus just 7.2 months in controls. This indicates CAN-2409's immunomodulatory effects may sensitize tumors to subsequent therapies, potentially changing the paradigm of how we approach treatment sequencing in pancreatic cancer.

The trial's immunological findings provide a mechanistic explanation: CAN-2409, a herpes simplex virus thymidine kinase gene therapy delivered intratumorally, transforms the typically immunosuppressive pancreatic tumor microenvironment. The observed dense infiltrates of CD8+ T cells and elevated pro-inflammatory markers suggest effective conversion of "cold" tumors to "hot" ones – precisely what's needed in pancreatic cancer's notoriously immunosuppressive environment.

However, the extremely small sample size (n=13 total) represents a significant limitation that investors should carefully consider. While the survival differences are striking, they could be influenced by chance or imbalances in prognostic factors between the arms.

From a commercial perspective, pancreatic cancer represents a $4+ billion market opportunity with approximately 60,000 new cases annually in the US and Europe. With Fast Track and Orphan designations already secured, CAN-2409 could potentially reach market with a smaller pivotal trial than typically required – though the company's announcement of plans for a "larger, late-stage trial" suggests they recognize the need for more robust data.

In the competitive landscape, CAN-2409's approach is differentiated from both standard cytotoxics and emerging immunotherapies that have largely disappointed in pancreatic cancer. The therapy's ability to create durable responses in some patients, including those with positive margins or even metastatic disease, positions it uniquely among development-stage pancreatic cancer treatments.

For investors, these results represent a significant de-risking event for Candel's pancreatic cancer program, though the path to market will require confirmation in a larger study. With a current market cap under $500M, successful development in this indication alone could drive substantial valuation growth given the significant unmet need and competition in effective pancreatic cancer therapies.

Biotechnology Investment Analyst

Candel Therapeutics' final Phase 2 data for CAN-2409 in pancreatic cancer represents a potential paradigm shift in one of oncology's deadliest malignancies. The 2.5-fold improvement in median survival (31.4 vs 12.5 months) is unprecedented in pancreatic cancer, where therapeutic advances typically yield survival benefits measured in weeks, not years.

What truly distinguishes these results is the long tail of survival – three of seven treated patients remain alive at 66.0, 63.6, and 35.8 months post-enrollment, dramatically exceeding the typical 1-year survival rates of ~20% for borderline resectable PDAC. Even more telling is the post-progression survival advantage (21.2 vs 7.2 months), suggesting CAN-2409 fundamentally alters tumor biology, potentially sensitizing cancers to subsequent therapies.

CAN-2409's mechanism – an adenoviral vector delivering herpes simplex virus thymidine kinase gene that converts prodrugs to cytotoxic agents within tumor cells while stimulating immune activation – appears particularly well-suited for pancreatic cancer's notoriously immunosuppressive microenvironment. The observed increases in tumor-infiltrating lymphocytes and pro-inflammatory markers confirm successful immune engagement, a feat that has eluded many immunotherapies in this indication.

From a market perspective, pancreatic cancer represents an estimated $4.2 billion opportunity with minimal innovation in decades. With approximately 60,000 new cases annually in the US and Europe and dismal 5-year survival rates below 10%, the commercial potential for effective therapies is substantial.

However, investors should carefully weigh the extremely small sample size (n=13) of this trial. While the magnitude of benefit is impressive, the patient numbers create uncertainty about reproducibility in larger populations. The company's decision to pursue a larger confirmatory trial acknowledges this limitation.

Financially, these results significantly de-risk Candel's pancreatic cancer program, building on their recent positive data in prostate cancer. With a current market cap of approximately $491 million, successful development in either indication could drive substantial valuation growth. However, the planned larger trial will require significant capital – a consideration for investors given the company will likely need additional financing to fully execute their clinical development strategy.

In the competitive landscape, CAN-2409 stands apart from both conventional treatments and other experimental approaches. While FOLFIRINOX and gemcitabine-based regimens remain standard first-line options, they offer durability. Among emerging therapies, most immunotherapy approaches have disappointed in pancreatic cancer, and targeted therapies address only small patient subsets.

With Fast Track and Orphan designations already secured, CAN-2409 has potential regulatory advantages that could accelerate its path to market. The favorable safety profile further enhances its risk-benefit proposition, especially important in a disease where quality of life considerations are paramount given survival expectations.

For investors, these results represent a significant milestone that enhances Candel's value proposition as a clinical-stage oncology company with multiple shots on goal in difficult-to-treat solid tumors.

• Positive final survival data after additional follow-up showed notable improvement in estimated median overall survival of 31.4 months after experimental treatment with CAN-2409 versus only 12.5 months in the control group in patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC).

• Three of seven patients treated with CAN-2409 were still alive with survival of 66.0, 63.6 and 35.8 months after enrollment, respectively. Survival from the time of diagnosis for these patients was 73.5, 68.8, and 41.3 months, respectively. Survival observed in these patients is well beyond the expected median overall survival for pancreatic cancer with standard of care, suggesting a long tail of survival.

• CAN-2409 safety profile was generally favorable in the phase 2 trial, further supporting the favorable safety profile to date associated with this investigational therapy across multiple indications.

• CAN-2409 previously received Fast Track Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of PDAC.
  

NEEDHAM, Mass., Feb. 25, 2025 (GLOBE NEWSWIRE) -- 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, today announced 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.

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:

• 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
  
  
  • 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).
    
  • Median survival post-progression was 21.2 months in patients who received CAN-2409 compared to 7.2 months in the control arm.
    
  • 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.
    
  • 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.

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

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

About Candel Therapeutics

Candel is a clinical stage biopharmaceutical company focused on developing off-the-shelf multimodal biological immunotherapies that elicit an individualized, systemic anti-tumor immune response to help patients fight cancer. Candel has established two clinical stage multimodal biological immunotherapy platforms based on novel, genetically modified adenovirus and HSV gene constructs, respectively. CAN-2409 is the lead product candidate from the adenovirus platform. CAN-3110 is the lead product candidate from the HSV platform and is currently in an ongoing phase 1b clinical trial in recurrent high-grade glioma (rHGG). Finally, Candel’s enLIGHTEN™ Discovery Platform is a systematic, iterative HSV-based discovery platform leveraging human biology and advanced analytics to create new viral immunotherapies for solid tumors.

For more information about Candel, visit: www.candeltx.com

Forward-Looking Statements

This press release includes certain disclosures that contain “forward-looking statements,” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, express or implied statements regarding the timing and advancement of current and future development programs; expectations regarding early biological readouts as predictor of clinical response; and expectations regarding the therapeutic benefit of the Company’s programs, including the ability of CAN-2409 to treat a broad range of solid tumors and improve disease-free survival, overall survival, and post-progression survival. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those risks and uncertainties related to the timing and advancement of development programs; expectations regarding the therapeutic benefit of the Company’s programs; that final data from the Company’s pre-clinical studies and completed clinical trials may differ materially from reported interim data from ongoing studies and trials; the Company’s ability to efficiently discover and develop product candidates; the Company’s ability to obtain and maintain regulatory approval of product candidates; the Company’s ability to maintain its intellectual property; the implementation of the Company’s business model, including strategic plans for the Company’s business and product candidates; and other risks identified in the Company’s filings with the U.S. Securities and Exchange Commission (SEC) including the Company’s most recent Quarterly Report on Form 10-Q filed with the SEC and subsequent filings with the SEC. The Company cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. The Company disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions, or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent the Company’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date.

Investor Contact:
Theodore Jenkins
VP, Investor Relations and Business Development
Candel Therapeutics, Inc.
tjenkins@candeltx.com

Media Contact:
Ben Shannon
ICR Healthcare
CandelPR@icrhealthcare.com

FAQ

What were the survival results of Candel Therapeutics' Phase 2 trial for CAN-2409 in pancreatic cancer?

The Phase 2 trial showed estimated median overall survival of 31.4 months in the CAN-2409 group versus 12.5 months in the control group. Three of seven CAN-2409-treated patients were still alive at 66.0, 63.6, and 35.8 months after enrollment, significantly exceeding expected survival rates for pancreatic cancer with standard treatment.

How does CAN-2409 work against pancreatic cancer according to Candel Therapeutics (CADL)?

CAN-2409 is a first-in-class multimodal immunotherapy designed for in situ vaccination against the patient's tumor. It activates the immune response, as evidenced by dense aggregates of CD8+ granzyme B+ cytotoxic tumor infiltrating lymphocytes, dendritic cells, and B cells in the tumor microenvironment, and increased levels of soluble granzymes and pro-inflammatory cytokines in peripheral blood.

What regulatory designations has CADL's CAN-2409 received for pancreatic cancer treatment?

CAN-2409 has received both Fast Track Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of pancreatic ductal adenocarcinoma (PDAC).

What is the safety profile of Candel Therapeutics' CAN-2409 in pancreatic cancer patients?

CAN-2409 demonstrated a favorable safety and tolerability profile when added to standard of care. The trial reported no dose-limiting toxicities and no cases of pancreatitis, supporting the favorable safety profile observed with this investigational therapy across multiple indications.

What are Candel Therapeutics' (CADL) next steps for CAN-2409 in pancreatic cancer after the positive Phase 2 results?

Based on the promising Phase 2 results, Candel Therapeutics has decided to prepare for a larger, late-stage randomized controlled clinical trial of CAN-2409 in pancreatic ductal adenocarcinoma (PDAC).

How did CAN-2409 affect patients with disease recurrence in the CADL pancreatic cancer trial?

Patients treated with CAN-2409 who experienced disease recurrence responded to salvage chemotherapy and had extended post-progression survival (median 21.2 months vs. 7.2 months in control arm), highlighting the sustained benefit of CAN-2409 even after cancer progression.