Valacyclovir Hydrochloride

▎药明康德内容团队编辑 Candel Therapeutics公司今日宣布，在研病毒免疫疗法CAN-2409与放疗联用，在治疗局部前列腺癌患者的3期临床试验中达到主要终点。在中高危患者中显著改善患者的无病生存期（DFS）。 这项随机双盲、安慰剂对照、多中心临床试验纳入了745名患者，旨在评估CAN-2409联合valacyclovir和标准外照射放疗对中高危局部前列腺癌患者无病生存期的改善效果及安全性。 CAN-2409是一种复制缺陷的腺病毒，可将编码单纯疱疹病毒胸苷激酶（HSV-tk）的基因递送入癌细胞。HSV-tk可以将口服的valacyclovir转化为有毒的代谢物acyclovir。该候选疗法通过直接注射到肿瘤组织内，可杀死局部的肿瘤细胞，导致微环境中肿瘤特异性新抗原的释放，进而激活全身的抗肿瘤应答。此外，局部注射将免疫应答局部聚焦于肿瘤，能够最大限度地减少与全身静脉给药相关的全身毒性。 试验结果显示： 在意向治疗人群中，CAN-2409联合放疗组（n=496）相比单纯放疗组（n=249），无病生存期显著改善（HR=0.7，p=0.0155）。 CAN-2409治疗组患者达到前列腺特异性抗原（PSA）最低点（<0.2 ng/ml）的比例显著增加（67.1%比58.6%；p<0.0164）。 CAN-2409治疗组患者中，在治疗两年后80.4%达到病理学完全缓解（pCR），对照组为63.6%（p=0.0015）。 CAN-2409的安全性与先前研究一致，未发现新的安全信号。最常见的不良事件包括流感样症状、发热和寒战，通常为轻度至中度。 仅在美国，每年就有超过10万名男性确诊为局部前列腺癌，其中超过5万人接受放射治疗。前列腺癌仍是美国男性癌症死亡的第二大原因，而在过去20多年里，局部非转移性前列腺癌的标准治疗并未发生重大变化或引入新疗法。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料： [1] Candel Therapeutics Announces CAN-2409 Achieved Primary Endpoint in Phase 3 Prostate Cancer Trial, Showing Significantly Improved Disease-Free Survival. Retrieved December 11, 2024, from https://www.globenewswire.com/news-release/2024/12/11/2995251/0/en/Candel-Therapeutics-Announces-CAN-2409-Achieved-Primary-Endpoint-in-Phase-3-Prostate-Cancer-Trial-Showing-Significantly-Improved-Disease-Free-Survival.html 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

NEEDHAM, MA, USA I December 11, 2024 I 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 results from a multicenter phase 3 clinical trial evaluating CAN-2409 viral immunotherapy in localized prostate cancer patients. In the United States alone, over 100,000 men are diagnosed with localized prostate cancer every year, and over 50,000 men currently receive radiotherapy. Prostate cancer continues to be the second leading cause of cancer death among men in the United States and there has not been any new treatment or significant change in the standard of care of localized, non-metastatic prostate cancer for over 20 years. The localized prostate cancer addressable market for CAN-2409 is potentially worth over $10 billion in the U.S. alone. The phase 3 clinical trial of CAN-2409 in intermediate-to-high-risk, localized prostate cancer met its primary endpoint, by demonstrating statistically significant improvement in disease-free survival in patients who received CAN-2409 plus prodrug (valacyclovir) combined with standard of care compared to standard of care alone. The 2:1 randomized, double-blind, placebo-controlled, multicenter clinical trial enrolled 745 patients (intent to treat population, ITT) to evaluate the effectiveness and safety of CAN-2409 plus prodrug (valacyclovir) viral immunotherapy in combination with standard of care external beam radiation therapy to improve disease-free survival (DFS) in patients with intermediate-to-high risk, localized prostate cancer. Patients were randomized and stratified for the use of short-term (< 6 months) androgen deprivation therapy (ADT). CAN-2409 is an investigational, off-the-shelf, replication-defective adenovirus that delivers the herpes simplex virus thymidine kinase (HSV-tk) gene to tumor cells. CAN-2409, when administered with valacyclovir, is designed to induce immunogenic cell death of tumor cells with exposure of tumor antigens in the context of an activated tumor microenvironment. Together, this regimen is designed to induce an individualized and specific CD8+ T cell-mediated response against the tumor, based on in situ vaccination against a variety of tumor antigens. Preclinical and clinical evidence suggests that CAN-2409 can be synergistic with local radiotherapy, providing further support for the design of the current phase 3 clinical trial. “The improvement observed in disease-free survival in this phase 3 clinical trial is clinically meaningful. We have not seen significant advances in this indication in decades. CAN-2409 has demonstrated the potential to significantly improve long-term outcomes without adding substantial toxicity to standard of care radiation,” said Glen Gejerman, M.D., MBA, Co-Director of Urologic Oncology at Hackensack Meridian Health, and one of the principal investigators of the study. “If approved, this approach has the potential to transform the treatment paradigm in prostate cancer, offering patients with localized disease an effective treatment option that may reduce the risk of disease recurrence.” Phase 3 Trial Results in Intermediate-High Risk Disease The study met its primary endpoint, demonstrating a statistically significant improvement in disease-free survival compared to the control arm. Key topline results include: The median follow-up time for the recruited population was 50.3 months. The primary outcome measure included the evaluation of post-treatment biopsies, performed at two years from the end of radiation, for the presence of tumor recurrence. Local or systemic recurrence and death from any cause were also part of the DFS endpoint. The safety profile of CAN-2409 was generally consistent with previous studies, with no new safety signals identified. The most common CAN-2409-related adverse events were flu-like symptoms, fever and chills, which were generally mild to moderate in severity and self-limited. The company also reported today that the phase 2 clinical trial of monotherapy CAN-2409 in 190 patients with low-to-intermediate risk localized prostate cancer undergoing active surveillance showed numerical improvement in time to radical treatment and the percentage of patients achieving negative (prostate cancer-free) biopsies at 1-year post-treatment. However, these differences did not reach statistical significance. The safety profile of CAN-2409 was generally consistent with that reported in the phase 3 clinical trial. “We are thrilled to report the phase 3 results for CAN-2409 in intermediate-to-high risk, localized prostate cancer,” said Paul Peter Tak, M.D., Ph.D., FMedSci, President and Chief Executive Officer of Candel. “This study validates previous observations of CAN-2409 activity seen in difficult-to-treat solid tumors, often resistant to immunotherapy, and confirms our previous observation of synergies with radiation therapy in models of prostate cancer. Importantly, this study was conducted under a Special Protocol Assessment (SPA) agreed with the U.S. Food and Drug Administration (FDA), on key aspects of study design, meaning that safety and efficacy data generated from the study could be sufficient for the Company to seek regulatory approval for CAN-2409 in this indication. We look forward to working with the FDA, as a next step, to seek approval to bring CAN-2409 to patients in the U.S., and advance our broad viral immunotherapy pipeline across other large oncology indications of high unmet need.” Based on these results, Candel intends to initiate discussions with the FDA regarding the regulatory pathway for CAN-2409 in intermediate-to-high-risk localized prostate cancer. The Company will present the totality of the data for both studies at upcoming medical conferences. Conference Call and Webcast Candel will host a webcast and conference call today at 8:30 a.m. EST. The webcast can be accessed (Here) and on the Candel website at www.candeltx.com under News & Events in the IR section of the website. An archived webcast will be available on Candel’s website for 30 days following the presentation. Participants may register for the conference call (Here) to receive the dial-in numbers and unique PIN to access the call seamlessly. It is recommended that you join 10 minutes prior to start of the event (although you may register and dial in at any time during the call). 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 without inordinate concern of overlapping adverse events. Currently, Candel is evaluating CAN-2409 in non-small cell lung cancer (NSCLC), borderline resectable pancreatic ductal adenocarcinoma (PDAC), and localized, non-metastatic prostate cancer in ongoing clinical trials. CAN-2409 plus prodrug (valacyclovir) has been granted Fast Track Designation by the U.S. Food and Drug Administration (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 primary prostate cancer. Candel’s pivotal phase 3 clinical trial in prostate cancer has been conducted under a Special Protocol Assessment agreed with the FDA. The FDA has also granted Orphan Drug Designation to CAN-2409 for the treatment of PDAC. 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 herpes simplex virus (HSV) gene constructs, respectively. CAN-2409 is the lead product candidate from the adenovirus platform and is currently in ongoing clinical trials in NSCLC (phase 2) and borderline resectable PDAC (phase 2), and recently completed phase 2b and phase 3 clinical trials in localized, non-metastatic prostate cancer. 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 SOURCE: Candel Therapeutics