Docetaxel

Phase 3 clinical trial will evaluate aglatimagene besadenovec plus valacyclovir in combination with continued pembrolizumab versus standard-of-care docetaxel chemotherapy in patients with metastatic, non-squamous, non-small cell lung cancer (NSCLC) with progressive disease despite prior pembrolizumab and platinum chemotherapy Global pivotal phase 3 trial expected to enroll patients in 1:1 randomization across more than 150 sites; first site now open for enrollment Primary endpoint is overall survival Candel has engaged Parexel International to support execution of this global pivotal trial NEEDHAM, Mass., June 30, 2026 (GLOBE NEWSWIRE) -- Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical-stage biopharmaceutical company focused on developing multimodal immunotherapies to improve disease outcomes for patients with cancer, today announced the initiation of the global pivotal phase 3 AURORA trial ( NCT07660094 ), evaluating aglatimagene besadenovec (aglatimagene or CAN-2409) plus valacyclovir in combination with continued pembrolizumab in patients with metastatic non-squamous NSCLC whose disease has progressed despite treatment with pembrolizumab and platinum-based chemotherapy. The global, randomized, open-label AURORA trial is expected to enroll patients with metastatic Stage IV non-squamous NSCLC across approximately 150 sites worldwide, randomized 1:1 to receive either aglatimagene plus valacyclovir for two injection courses with continued pembrolizumab, or standard-of-care docetaxel chemotherapy. The first trial site is activated and open to enrollment. The study’s primary endpoint is overall survival, with secondary endpoints including safety and quality-of-life assessments (NSCLC-SAQ and EORTC QLQ-30). The U.S. Food and Drug Administration (FDA) previously granted Fast Track Designation to aglatimagene for the treatment of NSCLC. To support the efficient global execution of this pivotal trial, Candel has engaged Parexel International, a leading global clinical research organization with extensive experience in oncology and a global network of nearly 2,500 sites. Parexel will provide clinical operations support across the trial's global sites. “Patients whose lung cancer progresses despite immune checkpoint inhibitor therapy have limited treatment options, and outcomes with standard chemotherapy remain poor,” said Roy Herbst, M.D., Deputy Director and Chief of Medical Oncology and Hematology at Yale Cancer Center and co-Principal Investigator of AURORA. “The survival results observed with aglatimagene in the phase 2 trial are particularly encouraging and support advancing the program into the pivotal phase 3 AURORA trial.” “The initiation of this first global phase 3 trial of a viral immunotherapy at NYU Langone Health marks an important milestone in advancing aglatimagene as a potentially first-in-class immunotherapy for patients with NSCLC,” said Daniel Sterman, M.D., Thomas and Suzanne Murphy Professor of Medicine and Cardiothoracic Surgery at NYU Langone Health and co-Principal Investigator. Charu Aggarwal, M.D., M.P.H., Leslye M. Heisler Professor of Medicine at the University of Pennsylvania’s Perelman School of Medicine; Section Chief, Thoracic and Head & Neck Cancer; and Director of the Penn Center for Cancer Care Innovation at the University of Pennsylvania is also a co-Principal Investigator on AURORA. The phase 3 AURORA trial builds on encouraging results from the Company’s phase 2 clinical trial ( NCT04495153 ), which demonstrated extended long-term survival in patients with advanced NSCLC who had shown an inadequate response to immune checkpoint inhibitors (ICI). In that trial, 50% of 46 per-protocol patients survived beyond 24 months despite prior inadequate response to ICI and multiple adverse baseline prognostic factors. Among evaluable patients with non-squamous histology and progressive disease at baseline despite prior ICI (intended patient population of the phase 3 trial), median overall survival was 25.4 months. “This is a pivotal moment for Candel and, most importantly, for the patients we aim to serve,” said Paul Peter Tak, M.D., Ph.D., FMedSci, President and Chief Executive Officer of Candel. “Disease progression following ICI therapy remains associated with poor survival outcomes and a substantial unmet medical need. Building on our completed phase 2 clinical trial, we have refined the target patient population by integrating clinical and biomarker insights to maximize the likelihood of success of the phase 3 trial. Our data suggest that aglatimagene may offer a novel approach by inducing an individualized, systemic anti-tumor immune response in patients who have very limited therapeutic options.” Lung cancer is the leading cause of cancer death in the United States, and NSCLC represents approximately 77% of all lung cancer cases. 1 Despite widespread use of ICI as first-line treatment for patients without actionable mutations, approximately 60% of patients experience disease progression within one year. 2 These patients face limited therapeutic options, with docetaxel remaining the current standard of care and delivering a median overall survival of just 9.8 to 11.8 months. 3,4 About aglatimagene besadenovec (CAN-2409) Aglatimagene besadenovec, 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 tumor. After intratumoral administration, HSV-tk enzyme activity results in conversion of prodrug (valacyclovir) into deoxyribonucleic acid (DNA)-incorporating nucleotide analogs, leading to immunogenic cell death in cells exhibiting DNA damage and proliferating cells, with subsequent release of a variety of tumor (neo)antigens in the tumor microenvironment. At the same time, the adenoviral serotype 5 capsid proteins promote inflammation through the induction of expression of pro-inflammatory cytokines, chemokines, and adhesion molecules. 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 immunization against a variety of tumor antigens. Aglatimagene 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 aglatimagene in clinical trials with a favorable tolerability pro date, supporting the potential for use with standard of care, when indicated. Aglatimagene is currently not approved by the FDA or any other regulatory authority for any use. 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. Aglatimagene is the lead product candidate from the adenovirus platform. The Company completed successful phase 2a clinical trials of aglatimagene in NSCLC and pancreatic ductal adenocarcinoma (PDAC), and a pivotal, placebo-controlled, phase 3 clinical trial of aglatimagene in localized prostate cancer, conducted under a Special Protocol Assessment agreed with the FDA and published in The Lancet Oncology . The FDA also granted Fast Track Designation and Regenerative Medicine Advanced Therapy Designation to aglatimagene for the treatment of newly diagnosed localized prostate cancer in patients with intermediate- to high-risk disease, Fast Track Designati on in NSCLC, and both Fast Track Designation and Orphan Drug Designation to aglatimagene for the treatment of PDAC. Linoserpaturev (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, evaluating the effects of repeat linoserpaturev injections. Initial results were published in Nature and Science Translational Medicine and linoserpaturev received Fast Track Designation and Orphan Drug Designation from the FDA. 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: . 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, including expectations regarding the enrollment of the phase 3 AURORA trial evaluating aglatimagene in NSCLC; expectations regarding early biological readouts as predictor of clinical response; expectations regarding the therapeutic benefit of the Company’s platforms, including the ability of its platforms to improve overall survival and/or disease-free survival of patients living with difficult-to-treat, solid tumors; and expectations regarding the potential benefits conferred by regulatory designations. 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 preclinical 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; the impact of the Company’s existing and any future indebtedness on its ability to operate its business; the Company’s ability to access any future tranches under its debt facility and to comply with all of its obligations thereunder; and other risks identified in the Company’s filings with the U.S. Securities and Exchange Commission (SEC), including the Company’s most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, each as filed with the SEC and any 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 Vice President, Investor Relations, and Business Development Candel Therapeutics, Inc. tjenkins@candeltx.com Media Contact Ben Shannon ICR Healthcare CandelPR@icrhealthcare.com [1] American Cancer Society. Cancer Facts & Figures 2026. [2] Gandhi L et al. NEJM 2018;378:2078-92 [3] Paz-Ares LG et al. J Clin Oncol 2024;42: 2860-2872 [4] Ahn MJ et al. J Clin Onc 2024;43:260-272

导语 肿瘤治疗所致血小板减少症（CTIT）是妇科肿瘤化疗过程中常见的剂量限制性毒性反应，严重影响治疗进程及患者预后。根据《中国临床肿瘤学会（CSCO）肿瘤治疗所致血小板减少症诊疗指南（2025版）》和《妇科肿瘤治疗相关血小板减少症临床管理专家共识》，重组人血小板生成素（rhTPO）被列为CTIT治疗的Ⅰ级推荐和首选药物1,2，具有起效迅速、疗效确切的优势。近年来，血小板生成素受体激动剂（TPO-RA）在CTIT治疗中逐渐受到关注，但其最佳给药策略、维持期剂量调整及长期安全性仍需进一步探索。尤其是在维持治疗阶段，如何实现血小板的平稳控制而不出现过度波动，是临床实践中亟待解决的问题。 本病例报道一例妇科肿瘤复发患者，在多次化疗周期中经历了三种不同的CTIT干预场景： 1、IL-11无效后切换：白介素-11治疗无效，切换为rhTPO后迅速有效； 2、Ⅳ度重症抢救：在rhTPO治疗基础上，因病情危重曾短暂加用拟肽类TPO-RA一次，血小板顺利恢复； 3、维持期波动：TPO-RA单药维持期间出现个体化的周期性血小板波动。 通过这三种场景的对比，本病例旨在探讨rhTPO在CTIT急性期治疗中的核心地位，以及TPO-RA在维持治疗中可能存在的调控挑战。 病例资料 一般资料 患者女性，39岁。诊断：子宫恶性肿瘤，平滑肌肉瘤，分期：rTXN1M1，IV期。既往接受多线化疗，反复出现CTIT。 第一次CTIT事件：IL-11无效，rhTPO“一锤定音” 时间节点：2024-12-15化疗后（患者既往经多线化疗） 基线血小板：化疗后血小板降低 初始干预：12-19与12-22予白介素-11（IL-11，1.5mg）升板治疗 疗效评估（失败）：2024-12-24 PLT为89×109/L（CTIT I级），血小板计数无明显回升，升板效果不理想。 切换干预：停用IL-11，切换至指南Ⅰ级推荐药物rhTPO 15000U，每日1次皮下注射 疗效评估（成功）：切换rhTPO后，血小板计数迅速回升，于2025-01-03恢复至157×109/L，顺利出院。 小结：本阶段验证了rhTPO在IL-11治疗失败后的迅速有效，凸显rhTPO作为CTIT治疗基石的地位。 图1：患者2024-12治疗后血小板计数变化情况 第二次CTIT事件： Ⅳ度血小板减少，rhTPO主导下的个体化处理 时间节点：2025-06-19化疗后 基线血小板：07-01查血常规显示血小板（PLT）60×109/L；07-03复查示血小板急剧下降至20×109/L（Ⅳ度血小板减少），出血风险高 主要干预：立即启用rhTPO 15000U每日皮下注射，连续7天 治疗经过：由于病情危重（Ⅳ度）且患者对rhTPO的既往反应良好，临床决定在rhTPO基础上短暂加用拟肽类TPO-RA一次（250μg，皮下注射），以期更快脱离危险。 疗效评估：治疗3天后：血小板回升至43×109/L（Ⅲ度），脱离危险区间；治疗7天后：血小板恢复至107×109/L（正常范围）。 小结：本次Ⅳ度重症CTIT的顺利恢复，显示了快速、强效的升板能力，其中rhTPO的每日持续促血小板生成作用为快速脱离危险提供了保障。 图2：患者2025-07治疗后血小板计数变化情况 后续CTIT预防： 拟肽类TPO-RA单药维持，周期性过度升高与回落 背景：后续治疗周期中，采用拟肽类TPO-RA单药二级预防方案 干预方案：规律给予拟肽类TPO-RA单药进行二级预防 血小板动态变化（多周期，模式重复）：拟肽类TPO-RA在本例中表现出一定的个体化药效学特点，给药后第1周：血小板维持在正常范围；给药后第2周：血小板超过正常值上限，最高达478×10⁹/L；给药后第3-4周：血小板逐渐回落 关键发现：每次给药均呈现“正常→过度升高（＞400×10⁹/L）→回落”的波动模式，多周期规律一致 潜在风险：周期性血小板过度升高（＞400×10⁹/L）可能增加血栓形成风险，需临床关注 图3：患者后续治疗期间（2025-08至2026-03）拟肽类TPO-RA单药治疗后血小板计数变化情况 讨论 rhTPO在CTIT急性期治疗中的核心地位：来自三种场景的验证 本病例通过三种不同的临床场景，充分展现了rhTPO在CTIT急性期治疗中的核心价值： 场景一（IL-11无效后切换）：当IL-11治疗无效时，切换至rhTPO后迅速起效，提示rhTPO应作为CTIT治疗的首选，而非补救用药； 场景二（Ⅳ度重症抢救）：Ⅳ度危急情况下，以rhTPO连续治疗为基础，3-5天快速起效，可有效、稳步提升PLT； 场景三（拟肽类TPO-RA维持期波动）：拟肽类TPO-RA的起效节律提示需重视动态监测与个体化调整，以更好兼顾升板疗效与安全性，周期性血小板过度升高（＞400×10⁹/L）可能增加血栓形成风险，需临床关注。 临床启示：合理定位，升板有度 1.急性期治疗：首选rhTPO，起效快、易调控，即使对于Ⅳ度重症，rhTPO单药也足以应对。 2.维持治疗需谨慎：对于出现周期性过度升高的患者，应评估血栓风险，考虑减量、延长给药间隔等。 3.个体化原则：同一患者对不同药物反应存在差异，CTIT管理不可“一刀切”。 结论 本病例通过同一患者多次化疗周期的三种CTIT干预场景，展示了rhTPO在CTIT管理中的重要价值： IL-11无效后切换，rhTPO快速有效，是治疗基石； Ⅳ度重症抢救，以rhTPO每日持续治疗为主，血小板可快速、稳步回升； 拟肽类TPO-RA的个体化药效学特点，提示临床应结合血小板动态变化，严格按照剂量调整原则进行管理，并在血小板升高至一定水平时及时减量、暂停或终止治疗。 整体而言，本病例提示，rhTPO应作为CTIT治疗首选药物，急性期救援与血小板平稳管控价值突出；并且需要根据患者不同阶段的临床需求及血小板动态变化，采取个体化调整策略，从而更好地平衡升板疗效、安全性与抗肿瘤治疗的连续性。 专家点评 CTIT是实体瘤系统治疗中常见的血液学毒性，其发生不仅与化疗药物种类、剂量强度和治疗周期累积有关，也受患者骨髓储备、既往多线治疗及肿瘤负荷等因素影响。现有研究和共识均提示，含吉西他滨、铂类等方案更易诱发血小板减少，而CTIT一旦发生，不仅增加出血和输血风险，还可能导致化疗延迟、剂量下调甚至治疗中断，最终影响抗肿瘤治疗强度和整体疗效2-4。因此，CTIT管理的核心并非单纯“把血小板升高”，而是尽可能抬高谷值、缩短危险期、减少输血依赖，并保障后续治疗连续性。 结合本例来看，患者为39岁晚期子宫平滑肌肉瘤患者，既往经历吉西他滨联合达卡巴嗪及多西他赛等多线化疗，期间经历剂量调整、手术减瘤及维持治疗，骨髓储备功能已明显下降，属于CTIT高风险人群。该病例中极具临床参考价值的信息在于：2024年12月患者化疗后出现血小板减少，在白介素-11升板治疗反应不佳的情况下，及时换用rhTPO后迅速获得良好升板应答，血小板顺利恢复至157×10⁹/L，提示患者对rhTPO仍具备良好敏感性。 至2025年7月，患者经吉西他滨联合多西他赛化疗后，血小板进一步降至20×10⁹/L，同时合并重度中性粒细胞缺乏，已进入出血与感染双重极高危窗口，此时治疗核心目标应为快速脱离危险阈值，而非被动等待自然恢复。临床于该节点及时采用rhTPO联合拟肽类TPO-RA双药升板策略，配合粒细胞刺激因子与抗感染支持治疗，患者血小板由低谷逐步回升至107×10⁹/L并平稳出院，首先体现了rhTPO在急性低谷期的快速纠偏和升板支持作用。 《中国肿瘤药物相关血小板减少诊疗专家共识（2023版）》明确提出，肿瘤CTIT患者在血小板计数<75×10⁹/L时可应用rhTPO，且治疗期间应动态监测血常规4；《妇科肿瘤治疗相关血小板减少症临床管理专家共识》则进一步指出，rhTPO可显著升高化疗后血小板最低值、缩短恢复至≥75×10⁹/L的时间，并将其列为妇科肿瘤CTIT治疗的1类推荐2。因此，本例的意义并不局限于“rhTPO能升板”，而在于它再次验证了：对于既往已有明确反应、且本周期迅速进入3~4级血小板减少的患者，rhTPO可作为低谷期救援的重要工具。 更具启示意义的是，患者在后续单用拟肽类TPO-RA治疗期间，血小板并非偶发性升高，而是在多个给药周期后持续出现反复异常升高，且多次超过正常上限。这提示在后续单用拟肽类TPO-RA治疗过程中，患者对促血小板生成刺激较为敏感，若未能根据血小板动态变化及时调整用药方案，血小板计数则可能由前期的恢复不足转为后期的异常升高。对此，妇科肿瘤专家共识明确指出，当血小板计数升高至正常范围以上时，理论上存在血栓形成或血栓栓塞并发症风险2，因此应严格按照剂量调整方案将血小板控制在目标范围内，并在超过一定水平时及时减量、暂停或终止治疗。 总体而言，本例较为完整地体现了rhTPO在妇科恶性肿瘤CTIT管理中的阶段化应用价值：在血小板深度下降的急性期，rhTPO可作为快速升板和支持治疗的重要手段，帮助患者尽快脱离出血高危状态；而在后续周期管理中，对于既往已发生明显CTIT的患者，rhTPO的应用价值不仅体现在低谷期救援，更体现在前移干预、开展二级预防，以提高血小板谷值、缩短危险期并保障抗肿瘤治疗的连续实施。与此同时，本例也提示，促血小板治疗的重点并非单纯追求持续升板或长期维持，而应依据患者血小板恢复特点和动态监测结果，及时调整后续用药策略。对于这类晚期妇科肿瘤患者，真正值得借鉴的临床经验，是在血小板低谷期及时干预，在恢复阶段注重动态评估和个体化调整，从而更好地平衡升板疗效、安全性及后续抗肿瘤治疗需求。 本文内容不可替代专业医疗建议、诊断或治疗，仅用于大众获取疾病和健康方面的知识科普不能用于自我诊断病情，所有内容仅供参考。 参考文献 1.CSCO肿瘤治疗相关血小板减少症诊疗指南（2025） 2.中华医学会妇科肿瘤学分会.现代妇产科进展,2026,35(03):161-172. 3.Kuter DJ. Haematologica. 2022;107(6):1243-1263. 4.中国抗癌协会肿瘤临床化疗专业委员会,等.中华医学杂志, 2023, 103(33): 2579-2590.