Valacyclovir Hydrochloride

▎药明康德内容团队编辑 皮下注射Keytruda达3期临床主要终点，今年9月有望获批 默沙东（MSD）公司今日报告了关键性3期临床试验3475A‑D77的数据。该研究评估了皮下注射的Keytruda（pembrolizumab）制剂MK-3475A与化疗联用的效果和安全性。这些结果已在2025年欧洲肺癌大会（ELCC）发布，并同时发表于Annals of Oncology。 该研究达到了主要终点：与静脉输注（IV）pembrolizumab联合化疗相比，MK-3475A联合化疗在药代动力学（PK）方面显示出非劣效性，且中位注射时间仅为2分钟。客观缓解率（ORR）、无进展生存期（PFS）、缓解持续时间（DOR）及安全性在两组之间保持一致。两组的中位总生存期均未达到。 基于这些数据，美国FDA已接受为皮下给药pembrolizumab递交的生物制品许可申请（BLA），拟在pembrolizumab此前获批的所有实体瘤适应症中，新增皮下给药方式。FDA预计在2025年9月23日之前完成审评。 针对免疫检查点抑制剂无效患者，创新溶瘤病毒疗法显著延长总生存期 Candel Therapeutics公司今日公布了在研疗法CAN‑2409，在治疗III/IV期非小细胞肺癌（NSCLC）患者的2a期临床试验的最终生存数据。在对免疫检查点抑制剂（ICI）应答不足的患者群体中，接受2个疗程CAN‑2409治疗的46名可评估患者的中位总生存期（mOS）为24.5个月。在基线时虽接受ICI治疗但病情进展的患者群体中，其mOS为21.5个月。相比之下，在其他研究中，对ICI治疗无效且接受标准治疗（如多西他赛化疗）的患者mOS为9.8–11.8个月。 CAN-2409是Candel公司的潜在“first-in-class”在研免疫疗法。它是一种复制缺陷的现货型腺病毒，可将表达单纯疱疹病毒胸苷激酶（HSV-tk）的转基因递送入患者肿瘤，从而诱导个体化的抗肿瘤免疫反应。HSV-tk是一种酶，可局部将口服药物valacyclovir转化为有毒代谢物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免疫反应。CAN-2409有潜力治疗多种实体瘤类型，先前已有多项临床前和临床研究显示了单药治疗以及与标准放疗、手术、化疗和免疫检查点抑制剂联合治疗的积极活性。 研究数据还显示，在尽管接受ICI治疗但病情进展的患者中，有37%在接受CAN‑2409治疗后两年仍存活。并且生物标志物研究显示，与鳞状组织学患者相比，非鳞状NSCLC患者在接受CAN‑2409后呈现更强的免疫学及临床应答，且该人群的mOS改善至25.4个月。 默沙东21价肺炎球菌结合疫苗在欧洲获批上市 默沙东公司日前宣布，欧盟委员会（EC）已批准Capvaxive（21价肺炎球菌结合疫苗）上市，用于对18岁及以上人群的主动免疫，以预防由肺炎链球菌（Streptococcus pneumoniae）血清型3、6A、7F、8、9N、10A、11A、12F、15A、15B、15C、16F、17F、19A、20A、22F、23A、23B、24F、31、33F和35B引起的侵袭性疾病和肺炎。 Capvaxive的预防效力得到关键性3期临床试验STRIDE-3数据的支持。该研究评估了Capvaxive与活性对照药物PCV20（肺炎球菌20价结合疫苗）相比，在以前未接种过肺炎球菌疫苗的成人中的免疫原性、耐受性和安全性。 该试验主要终点的分析显示，根据第30天血清型特异性调理吞噬活性（OPA）几何平均滴度（GMTs）的测量结果，在50岁及以上成人（队列1）中，Capvaxive与活性对照药物共有的10种血清型中，Capvaxive引起的免疫应答呈现非劣效性。根据第30天OPA GMT的测定结果以及从第1天至第30天OPA升高≥4倍的患者比例，Capvaxive中包含的11种独特血清型中有10种展现良好的免疫应答，活性对照疫苗不包含这11种血清型。此外，根据接种后30天血清型特异性OPA GMTs的评估，与50-64岁的成人相比，18-49岁的成人（队列2）中Capvaxive引起的免疫应答展现非劣效性。 ▲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 Reports Both Prolonged Median Overall Survival and Long Tail of Survival in Phase 2a Clinical Trial of CAN-2409 in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Non-Responsive to Immune Checkpoint Inhibitor (ICI) Treatment. Retrieved March 27, 2025, from https://www.globenewswire.com/news-release/2025/03/26/3050122/0/en/Candel-Therapeutics-Reports-Both-Prolonged-Median-Overall-Survival-and-Long-Tail-of-Survival-in-Phase-2a-Clinical-Trial-of-CAN-2409-in-Advanced-Non-Small-Cell-Lung-Cancer-NSCLC-Pat.html [2] Merck’s Investigational Subcutaneous Pembrolizumab With Berahyaluronidase Alfa Demonstrates Noninferior Pharmacokinetics Compared to Intravenous (IV) KEYTRUDA® (pembrolizumab) in Pivotal 3475A-D77 Trial. Retrieved March 27, 2025, from https://www-merck-com.libproxy1.nus.edu.sg/news/mercks-investigational-subcutaneous-pembrolizumab-with-berahyaluronidase-alfa-demonstrates-noninferior-pharmacokinetics-compared-to-intravenous-iv-keytruda-pembrolizumab-in-pivotal/ [3] European Commission (EC) Approves Merck’s CAPVAXIVE® (Pneumococcal 21-valent Conjugate Vaccine) for Prevention of Invasive Pneumococcal Disease and Pneumococcal Pneumonia in Adults. Retrieved March 27, 2025, from https://www.businesswire.com/news/home/20250326133700/en/European-Commission-EC-Approves-Mercks-CAPVAXIVE-Pneumococcal-21-valent-Conjugate-Vaccine-for-Prevention-of-Invasive-Pneumococcal-Disease-and-Pneumococcal-Pneumonia-in-Adults 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 March 26, 2025 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 final survival data from a phase 2a clinical trial of CAN-2409 in patients with stage III/IV NSCLC, inadequately responding to ICI treatment. mOS was 24.5 months in 46 evaluable patients receiving 2 courses of CAN-2409 (per protocol population; cohort 1 and 2) and 21.5 months in evaluable patients from cohort 2 (n=41) that presented with progressive disease at baseline, despite ICI treatment. mOS in patients with progressive disease despite ICI treatment, was 9.8-11.8 months in other studies, including those with standard of care of docetaxel chemotherapy, which has a very poor prognosis, did not exceed 12 months in other published studies. (1, 2) This final analysis included extended follow-up data (1 year after the previous data cut) with a median follow up time for the per protocol population of 32.4 months. Data showed a sizable percentage of patients with survival exceeding 24 months, evidence of a long tail of survival, with 37% of patients with progressive disease despite treatment with ICI alive 2 years after CAN-2409 administration. Biomarker research showed an enhanced immunological and clinical response after CAN-2409 administration in patients with non-squamous histology compared to squamous histology, and improved mOS was observed in this population (25.4 months in patients with progressive disease despite ICI treatment and non-squamous NSCLC, n=33). “Treatment options are quite limited for patients with unresectable NSCLC who progress on anti-PD-1 therapy,” said Charu Aggarwal, MD, MPH, Leslye Heisler Professor for Lung Cancer Excellence at the University of Pennsylvania’s Perelman School of Medicine and Principal Investigator of the study. “The survival benefit seen in this study is striking, especially when compared to both the current standard of care treatment of docetaxel chemotherapy and other therapies under investigation for this patient group,” she added. Data Highlights: Pre-treatment and mid-treatment dropout rates were comparable to those reported in other clinical trials in similar populations of patients with advanced NSCLC. (1, 3) Three patients were enrolled, but did not receive treatment, 22 patients received only one injection of CAN-2409, 51 patients received at least 2 injections of CAN-2409, but 5 patients did not complete treatment. 46 patients received complete treatment (2 courses of CAN-2409 plus prodrug) and were included in the evaluable, per protocol population. The per protocol population was representative of the overall enrolled population in terms of baseline demographics and prognostic factors. “These updated survival data confirm and strengthen our previously reported findings, demonstrating that CAN-2409 has the potential to extend survival for patients with advanced NSCLC, who have limited treatment options after failing to respond to, or progressing, despite immune checkpoint inhibitor therapy,” said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. “CAN-2409 may represent an entirely new approach to solid tumor treatment, with its unique mechanism of action and favorable safety profile to date, enabling potentially meaningful improvements in outcomes beyond current standard of care. These compelling results mark a potentially transformative advance in our fight against this aggressive disease.” “The extension of survival in patients with non-squamous disease is notable even when compared to data that have been reported for other investigational products, such as antibody-drug conjugates, for this patient population,” said W. Garrett Nichols, MD, CMO of Candel. “CAN-2409, in addition to continued ICI treatment, may prolong survival beyond that offered by docetaxel chemotherapy, and has the potential to be better tolerated.” Based on these positive findings, the Company will advance its development program for CAN-2409 in NSCLC, including preparation and enabling work for a future, potentially registrational, clinical trial in patients with NSCLC with non-squamous histology. The U.S. Food and Drug Administration (FDA) previously granted Fast Track Designation for CAN-2409 plus valacyclovir in combination with ICI treatment for the treatment of 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. About CAN-2409 CAN-2409, Candel’s most advanced multimodal biological immunotherapy candidate, is an investigational, off-the-shelf, replication-defective adenovirus engineered 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 nucleotide analogue 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. Candel’s clinical development program for CAN-2409 includes completed phase 2a clinical trials in both non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC), as well as a positive pivotal randomized, placebo-controlled phase 3 clinical trial of CAN-2409 in localized, non-metastatic prostate cancer. In December 2024, Candel announced that CAN-2409 achieved its primary endpoint in a phase 3 clinical trial in men with intermediate-to-high-risk, localized prostate cancer, demonstrating statistically significant and clinically meaningful improvement in disease-free survival when added to SoC radiation therapy +/- androgen deprivation therapy. In the Company’s randomized controlled phase 2a clinical trial of CAN-2409 in borderline resectable PDAC, positive survival data showed notable improvement in estimated median overall survival of 31.4 months after experimental treatment with CAN-2409 plus standard of care versus 12.5 months in the control group in patients with PDAC, who received only standard of care. Median survival post-progression was 21.2 months in patients who received CAN-2409 compared to 6.4 months in the control arm. 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 primary 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 newly diagnosed, localized prostate cancer was conducted under a Special Protocol Assessment (SPA) agreed with the FDA. About Candel Therapeutics Candel is a BLA ready 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. 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. In October 2023, the Company announced that Nature published initial results from this ongoing clinical trial: CAN-3110 was well tolerated and the investigators observed nearly two-fold increase in median overall survival compared to historical controls after a single CAN-3110 injection in this therapy-resistant condition. 4 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 1 Paz-Ares LG et al. J Clin Oncol 2024;42:2860-2872 2 Ahn MJ et al. J Clin Onc 2024;43:260-272 3 Reckamp,KL et al. J Clin Oncol. 2022; 40 :2295-2306 4 Ling AL, et al. Nature. 2023;623(7985):157-166. SOURCE: Candel Therapeutics