The standard of care for intermediate to high-risk localized prostate cancer includes surgery or external beam radiation therapy (EBRT) with or without short-term androgen deprivation therapy (ADT). However, nearly 30% of patients receiving EBRT experience disease recurrence, often requiring additional treatments that can adversely affect quality of life. 

CAN-2409 is a replication-defective adenovirus delivering the HSV-tk gene, which, when combined with the prodrug valacyclovir, induces immunogenic cell death and promotes long-term tumor control through immune activation. In May 2025, Candel Therapeutics secured the FDA RMAT designation for CAN-2409 in localized prostate cancer in patients with intermediate-to-high-risk disease. CAN-2409 was also previously granted FDA Fast Track designation for the same indication. RMAT status, backed by positive Phase III data, positions CAN-2409 for expedited review as a novel immunotherapy for intermediate-to-high-risk prostate cancer. A Phase III, double-blind, placebo-controlled trial (NCT01436968) was conducted to evaluate the efficacy of CAN-2409 plus prodrug alongside EBRT±ADT in 745 prostate cancer patients, with disease-free survival as the primary endpoint and a median follow-up of over 50 months.

At the 2025 ASCO Annual Meeting, Phase III trial results showed that CAN-2409 plus an oral prodrug, combined with standard EBRT, significantly improved disease-free survival in patients with intermediate-to-high-risk localized prostate cancer—marking a potential advance over EBRT alone. CAN-2409 plus valacyclovir in intermediate-to-high-risk localized prostate cancer demonstrated a significant 30% reduction in the risk of disease recurrence or death compared to placebo after a median follow-up of 50.3 months. Patients not receiving ADT showed an even greater benefit, especially those with favorable intermediate-risk disease. CAN-2409 also significantly improved prostate cancer-specific disease-free survival and increased the proportion of patients achieving a PSA nadir below 0.2 ng/ml.Additionally, overall survival (OS) outcomes were similar across treatment arms, with 1 death due to disease progression in each arm; 50 patients died to causes unrelated to treatment.

Pathological complete response (pCR) rates at 2-year biopsies were significantly higher with CAN-2409 (80.4%) versus placebo. Positive biopsies two or more years post-radiotherapy correlated strongly with higher risks of biochemical failure, distant metastasis, and prostate cancer-related mortality. Overall survival was similar between treatment arms, with only one death due to disease progression reported in each group, and 50 deaths attributed to causes unrelated to treatment.

The treatment was generally well tolerated; common adverse effects were infection-like symptoms including chills, influenza-like illness, fever, and fatigue. Rates of urinary frequency, nausea, and headaches were comparable between groups. Serious treatment-related adverse events were low and similar between CAN-2409 (1.7%) and placebo (2.2%), with treatment discontinuation rates also comparable (5.4% vs 6.0%).

KOL insights

CAN-2409 significantly increased the proportion of patients achieving DFS when added to SOC EBRT in patients with intermediate-to-high-risk prostate cancer, reducing that relative risk by 30%, CAN-2409, with these efficacy findings and because it was well tolerated, represents a first possible paradigm shift in the treatment of men with localized prostate cancer in over 20 years.– Expert Opinion

The highly variable nature of recurrent prostate cancer poses clinical challenges, and nearly up to 40% of patients who undergo radical prostatectomy, and up to 50% of the patients who undergo radiation therapy is likely to develop local or distant recurrences within 10 years.”– Expert Opinion

Conclusion

CAN-2409 combined with EBRT demonstrated a significant 30% reduction in the risk of disease recurrence or death in patients with intermediate-to-high-risk localized prostate cancer. The benefits were especially pronounced in patients not receiving androgen deprivation therapy, notably those with favorable intermediate-risk disease. Additionally, CAN-2409 improved prostate cancer-specific disease-free survival and pathological complete response rates, with more patients achieving a low PSA nadir below 0.2 ng/ml. The treatment was generally well tolerated, with manageable infection-like side effects, positioning CAN-2409 as a promising new approach that could potentially transform the management of localized prostate cancer.

The prostate cancer treatment landscape is highly competitive, led by established therapies like Janssen’s XTANDI and Astellas/Pfizer’s ZYTIGA, which remain key players despite generic competition impacting ZYTIGA’s revenue. Newer entrants such as Bayer’s NUBEQA and Janssen’s ERLEADA are gaining traction, while innovative therapies including Novartis’ radioligand PLUVICTO and PARP inhibitors from AstraZeneca and others are expanding treatment options, especially for patients with specific genetic mutations. The pipeline is robust with promising candidates from companies like ESSA Pharma, Arvinas, and Daiichi Sankyo, though most have yet to enter late-stage trials. Growing prostate cancer prevalence and ongoing label expansions, along with emerging therapies, are expected to drive market growth, even as the disease’s aggressive nature continues to pose clinical challenges.