The purpose of this clinical trial is to evaluate the effects of adding CAN-2409 + prodrug for stage III/IV NSCLC patients who are on standard of care first line immune checkpoint inhibitor (ICI) treatment with evidence that the clinical response is inadequate. CAN-2409 is a viral immunotherapy approach that induces tumor-infiltrating T-cells and a consequent PD-L1 up-regulation. A combination of CAN-2409 added to standard of care (SOC) checkpoint inhibitors may lead to improved long-term outcomes for patients with NSCLC who have suboptimal response to ICI therapy.

开始日期2020-10-13

申办/合作机构

Candel Therapeutics, Inc.

[+1]

NCT03603405 / Recruiting临床1/2期IIT

Phase I-II Study Evaluating HSV-tK + VALACYCLOVIR GENE THERAPY Combination With Radiotherapy and Chemotherapy for Newly Diagnosed Anaplastic Astrocytoma and Glioblastoma Multiforme.

Study to assess the safety and efficacy of HSV-tk (gene therapy), valacyclovir, radiotherapy and chemotherapy in newly diagnosed glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA).

开始日期2018-02-28

申办/合作机构

THE METHODIST HOSP RESEARCH INSTITUTE

100 项与 Aglatimagene besadenovec 相关的临床结果

登录后查看更多信息

100 项与 Aglatimagene besadenovec 相关的转化医学

登录后查看更多信息

100 项与 Aglatimagene besadenovec 相关的专利（医药）

登录后查看更多信息

176

项与 Aglatimagene besadenovec 相关的文献（医药）

2023-10-03·Expert opinion on biological therapy

Oncolytic virotherapies for pediatric tumors

Review

作者: Atchley, Travis J ; Johnston, James M ; Laskay, Nicholas Mb ; Markert, James M ; Estevez-Ordonez, Dagoberto ; Gross, Evan G ; Hamo, Mohammad A

INTRODUCTION:

Many pediatric patients with malignant tumors continue to suffer poor outcomes. The current standard of care includes maximum safe surgical resection followed by chemotherapy and radiation which may be associated with considerable long-term morbidity. The emergence of oncolytic virotherapy (OVT) may provide an alternative or adjuvant treatment for pediatric oncology patients.

AREAS COVERED:

We reviewed seven virus types that have been investigated in past or ongoing pediatric tumor clinical trials: adenovirus (AdV-tk, Celyvir, DNX-2401, VCN-01, Ad-TD-nsIL-12), herpes simplex virus (G207, HSV-1716), vaccinia (JX-594), reovirus (pelareorep), poliovirus (PVSRIPO), measles virus (MV-NIS), and Senecavirus A (SVV-001). For each virus, we discuss the mechanism of tumor-specific replication and cytotoxicity as well as key findings of preclinical and clinical studies.

EXPERT OPINION:

Substantial progress has been made in the past 10 years regarding the clinical use of OVT. From our review, OVT has favorable safety profiles compared to chemotherapy and radiation treatment. However, the antitumor effects of OVT remain variable depending on tumor type and viral agent used. Although the widespread adoption of OVT faces many challenges, we are optimistic that OVT will play an important role alongside standard chemotherapy and radiotherapy for the treatment of malignant pediatric solid tumors in the future.

2023-10-01·Human gene therapy

Clinical Efficacy and Safety of AdV-tk Gene Therapy for Patients with Cervical Squamous Intraepithelial Lesion: A Prospective Study.

Article

作者: Tang, Huadong ; Li, Yanmei ; Liu, Xin ; Liu, Qing ; Hou, Ying ; Zhou, Yuxiang ; Li, Ning ; Li, Xiulan ; Bian, Meina ; Wang, Nan ; Xu, Fuqiang

Cervical cancer is the fourth most common type of cancer for women in 2020, and many more women have cervical precancerous lesion-squamous intraepithelial lesion (SIL). Early treatment of cervical SIL to reverse or delay its progression is an important approach to reduce the incidence of cervical cancer. The efficacy and safety of adenovirus-based vectors expressing the thymidine kinase gene (AdV-tk) in the treatment of multiple types of cancers shows promise for its use in gynecology. We aim to provide relevant clinical efficacy and safety data after introducing AdV-tk for the treatment of cervical SIL for the first time through this prospective study. We conducted a maximum of 6 sessions to administer AdV-tk gene therapy to 23 patients (mean age: 35 years old) with cervical low-/high-grade SIL (LSIL/HSIL) who were enrolled from August 2015 to April 2018 and analyzed the clinical characteristics and follow-up outcomes (mean follow-up period: 7.3 months). The present study consisted of 17 patients (73.9%) with cervical HSIL and 6 patients with LSIL confirmed by colposcopy-directed biopsy. We observed an overall histological remission and regression rate of 87.0% (20/23, 95% confidence interval [95% CI]: 73.2-100, p < 0.001) after AdV-tk gene therapy. Eight patients (34.8%) were detected with human papillomavirus (HPV) 16/18 subtypes and 13 patients were found to be positive with at least one of the other 13 high-risk HPV (HR-HPV) subtypes, while 2 patients did not have any of the 15 HR-HPV subtypes. The overall clearance rate of HR-HPV was 76.2% (16/21, 95% CI: 58.0-94.4, p = 0.016) after AdV-tk gene therapy. For safety evaluation, no severe complications were reported in any of the 23 patients. The most commonly reported symptom was fever in 52.2% (12/23) of patients and all symptoms were fully resolved after symptomatic treatment. Our data indicate that AdV-tk gene therapy has high efficacy and safety in the treatment of cervical SIL among gynecological patients. Our findings provide clinical evidence on the potential promotion and application of AdV-tk in the treatment of cervical SIL, and potentially for cervical cancer, among gynecological patients.

2023-10-01·Molecular therapy : the journal of the American Society of Gene Therapy

Combined cytotoxic and immune-stimulatory gene therapy using Ad-TK and Ad-Flt3L: Translational developments from rodents to glioma patients

Review

作者: Castro, Maria G ; Lowenstein, Pedro R ; Faisal, Syed M

Gliomas are the most prevalent and devastating primary malignant brain tumors in adults. Despite substantial advances in understanding glioma biology, there have been no regulatory drug approvals in the US since bevacizumab in 2009 and tumor treating fields in 2011. Recent phase III clinical trials have failed to meet their prespecified therapeutic primary endpoints, highlighting the need for novel therapies. The poor prognosis of glioma patients, resistance to chemo-radiotherapy, and the immunosuppressive tumor microenvironment underscore the need for the development of novel therapies. Gene therapy-based immunotherapeutic strategies that couple the ability of the host immune system to specifically kill glioma cells and develop immunological memory have shown remarkable progress. Two adenoviral vectors expressing Ad-HSV1-TK/GCV and Ad-Flt3L have shown promising preclinical data, leading to FDA approval of a non-randomized, phase I open-label, first in human trial to test safety, cytotoxicity, and immune-stimulatory efficiency in high-grade glioma patients (NCT01811992). This review provides a thorough overview of immune-stimulatory gene therapy highlighting recent advancements, potential drawbacks, future directions, and recommendations for future implementation of clinical trials.

项与 Aglatimagene besadenovec 相关的新闻（医药）

2024-07-01

·PRNewswire

Oncolytic Viruses: Unlocking a New Era in Cancer Immunotherapy | DelveInsight

The potential of oncolytic viruses as a novel approach to cancer treatment is exciting and offers a targeted approach that holds promise for overcoming treatment resistance and achieving durable responses in a range of malignancies. LAS VEGAS, July 1, 2024 /PRNewswire/ -- Oncolytic viruses are either RNA or DNA viruses. RNA viruses such as reoviruses, paramyxoviruses, and picornaviruses, which encode only a few genes, often undergo rapid proliferation and lysis of tumor cells. On the other hand, oncolytic DNA viruses such as herpes viruses, adenoviruses, or poxviruses allow for the insertion of multiple foreign genes but are slower in replication and amplification. Among the selected cancers, bladder cancer accounted for the maximum cases as compared to other selected indications in 2023 among the 7MM. As per the DelveInsight assessment, in 2023, the total incident cases of melanoma, non-melanoma skin cancer, pancreatic cancer, renal cell carcinoma, prostate cancer, brain cancer, bladder cancer, and ovarian cancer combined in the United States were 1.1 million. Currently, only two oncolytic virus therapies are approved, namely, IMLYGIC (Talimogene laherparepvec/T-VEC; Amgen) and DELYTACT (teserpaturev/G47∆; Daiichi Sankyo). Learn more about the FDA-approved oncolytic viruses @ Oncolytic Viruses Cancer Treatment IMLYGIC (T-VEC), developed by Amgen, became the first oncolytic virus to receive approval from the FDA in 2015. It is indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with recurrent melanoma following initial surgery. Subsequently, in December 2015, the European Commission (EC) also approved for its use in treating adults with unresectable melanoma that has regionally or distantly metastasized (Stage IIIB, IIIC, and IVM1a), excluding bone, brain, lung, or other visceral diseases. This genetically modified herpes simplex virus type 1 is engineered to replicate within tumors and express an immune-stimulating protein known as granulocyte-macrophage colony-stimulating factor (GM-CSF). DELYTACT (G47Δ) is a modified form of herpes simplex virus type 1 (HSV-1) with three mutations, designed to selectively replicate within cancer cells. In 2021, it received provisional approval from the Japan Ministry of Health, Labour and Welfare (MHLW) for hospital-based commercialization, specifically for treating malignant glioma patients over 7 years. This approval followed a Phase II trial demonstrating improved one-year survival rates among patients with recurrent glioblastoma, previously treated with radiotherapy and temozolomide chemotherapy. DELYTACT marks the world's first oncolytic virus therapy for brain cancer and only the third globally available oncolytic virus treatment. To learn more about oncolytic viruses cancer treatment options, visit @ Oncolytic Virus Cancer Therapy The field of oncolytic virus therapy is still developing. Further research is needed to determine their long-term efficacy and potential challenges. Still, early results seem encouraging, suggesting that oncolytic viruses may become a powerful tool for the treatment of patients with cancer. Presently, oncolytic virus therapy is only approved for melanoma and malignant glioma (in Japan). However, the pipeline suggests its emergence as a potential treatment for various cancers, including ovarian cancer, non-small cell lung cancer, breast cancer, renal cell carcinoma, and others. The pipeline for oncolytic viruses is robust, with major pharmaceutical companies such as Replimune (RP1), Genelux (Olvi-Vec), Candel Therapeutics (CAN-2409), Imugene (CF33-HNIS), EpicentRx (AdAPT-001), and others actively engaged in research to enhance cancer treatment options. Discover which therapies are expected to grab major oncolytic virus therapy market share @ Oncolytic Virus Therapy Market Report Olvi-Vec is a proprietary oncolytic vaccinia virus engineered to enhance safety, tumor selectivity, and therapeutic potential. Originally a non-human pathogen used in the smallpox vaccine, the vaccinia virus induces immunogenic cell death and activates the immune system for long-term cancer immunotherapy. According to Genelux's recent corporate presentation, topline results for the Phase III OnPrime/GOG-3076 study are expected in the second half of 2025. In November 2023, Genelux announced that the US FDA granted Fast Track Designation for Olvi-Vec (olvimulogene nanivacirepvec) in treating patients with platinum-resistant/refractory ovarian cancer. The drug is currently in Phase III clinical development, with the study anticipated to be completed by 2026. RP1 is Replimune's leading product candidate, developed from a proprietary new strain of herpes simplex virus. It has been genetically modified and enhanced with a fusogenic protein (GALV-GP R-) and GM-CSF to enhance tumor-killing potency, improve the immunogenicity of tumor cell death, and stimulate a systemic anti-tumor immune response. In April 2024, Replimune presented interim results from ARTACUS, a Phase I/II clinical trial testing RP1 monotherapy for skin cancers in patients who have undergone solid organ or hematopoietic cell transplants. Currently, RP1 is in the Phase II IGNYTE study, a multi-cohort clinical trial combining RP1 with OPDIVO. AdAPT-001 is an experimental immunotherapy featuring a TGF-β receptor-immunoglobulin Fc fusion trap. It is designed to neutralize isoforms 1 and 3 of the profibrotic, proangiogenic, prohypoxic, and immunosuppressive cytokine, TGF-β, and make resistant tumors more responsive to checkpoint blockade. In the ongoing Phase I/II BETA PRIME trial, AdAPT-001 is being administered alone and in combination with checkpoint inhibitors to patients with treatment-resistant tumors. Notably, AdAPT-001 combined with checkpoint inhibitors has shown improved toxicity and adverse event profiles compared to the typical results seen with checkpoint inhibitors alone. Discover more about oncolytic viruses in development @ Oncolytic Viruses Cancer Therapy Clinical Trials The anticipated launch of these emerging therapies are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the oncolytic virus cancer therapy market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the market size for oncolytic virus therapy is expected to grow with a significant CAGR by 2034. As per DelveInsight, the United States accounts for the largest oncolytic virus market size accounting for more than 70% of the total market, in comparison to EU4 (Germany, Spain, Italy, France), the United Kingdom, and Japan. Among all the emerging oncolytic virus therapies, RP1 is the most promising therapy accounting for ~40% of the oncolytic virus market in the coming decade due to its high efficacy. DelveInsight's latest published market report titled as Oncolytic Virus Market Size, Target Population, Competitive Landscape & Market Forecast – 2034 will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the oncolytic virus country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The oncolytic virus market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Incident Cases of Selected Cancer Types Target Patient Pool of Oncolytic Virus Cancer Therapy by Cancer Types Total Treated Cases by Line of Therapies The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM oncolytic virus market. Highlights include: 11-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this oncolytic virus market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the oncolytic virus market. Also, stay abreast of the mitigating factors to improve your market position in the oncolytic virus therapeutic space. Related Reports Oncolytic Virus Competitive Landscape Oncolytic Virus Competitive Landscape – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key oncolytic virus companies, including Genelux Corporation, Candel Therapeutics, CG Oncology, DNAtrix, SillaJen Biotherapeutics, Oncolytics Biotech, Wuhan Binhui Biotechnology, Oryx GmbH, Jiangsu Sinorda Biomedicine Co., Ltd, Virogin Biotech, Replimune, Viralytics, Oncolys Biopharma, Istari Oncology, Immvira Pharma, Seneca Therapeutics, Treovir, LLC, Targovax, Lokon Pharma, ORCA Therapeutics, Beijing SyngenTech, ViruCure, Tasly Pharmaceuticals, Turnstone Biologics, BioInvent, Transgene, Elicera Therapeutics, Orgenesis, Virttu Biologics, Imugene, Astellas Pharma, Wuhan Binhui Biotechnology Co., Ltd., Mustang Bio, Virogin Biotech, Vaxiion Therapeutics, ImmVirX, Memgen, Replimune, Immvira Pharma, ViroCure, GeneMedicine, PsiOxus Therapeutics, VCN Biosciences, Candel therapeutics, Sorrento Therapeutics, Imugene Limited, Calidi Biotherapeutics, Replimune, TILT Biotherapeutics, Guangzhou Virotech Pharmaceutical, DNAtrix, Oncorus, BioEclipse Therapeutics, among others. Oncology Drugs Market Oncology Drugs Market Insight, Competitive Landscape, and Market Forecast – 2030 report delivers an in-depth understanding of market trends, market drivers, market barriers, and key oncology drugs companies, including GlaxoSmithKline, Eli Lilly & Company, F. Hoffmann-La Roche Ltd, AbbVie Inc., Amgen Inc, Sanofi, Merck & Co., Inc, Novartis AG, Pfizer Inc, AstraZeneca, Bristol Myers Squibb., Gilead Sciences, Inc., Janssen Global Services, LLC, BAYER AG., Celldex Therapeutics Inc., Alaunos Therapeutics, Inc., Astellas Pharma Inc., Genentech, Inc., Sandoz International GmbH, BeiGene, among others. Melanoma Market Melanoma Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key melanoma companies including IO Biotech, Merck Sharp & Dohme, Eisai, Regeneron Pharmaceuticals, Iovance Biotherapeutics, Highlight Therapeutics, Linnaeus Therapeutics, Spring Bank Pharmaceuticals, Taiga Biotechnologies, Inc., Aivita Biomedical, Inc., Genentech, Inc., Dana-Farber Cancer Institute, BioMed Valley Discoveries, Inc, Amgen, Checkmate Pharmaceuticals, Astellas Pharma Inc, Galectin Therapeutics Inc., Eucure (Beijing) Biopharma Co., Ltd, Mologen AG, Ultimovacs ASA, Seagen Inc., MedImmune LLC, OnKure, Inc., Syntrix Biosystems, Inc., Anaveon AG, iOx Therapeutics, Portage Biotech, ModernaTX, Inc., Nektar Therapeutics, BioNTech SE, Sapience Therapeutics, HUYABIO International, LLC., Provectus Biopharmaceuticals, Inc., Cantargia AB, Turnstone Biologics, Corp., Aura Biosciences, F-star Therapeutics, Inc., Day One Biopharmaceuticals, Inc., Kinnate Biopharma, Xencor, Inc., HiFiBiO Therapeutics, among others. Pancreatic Cancer Market Pancreatic Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key pancreatic cancer companies including FibroGen, OSE Immunotherapeutics, Lokon Pharma, Oncotelic Inc., Tesaro, Inc., Helix BioPharma Corporation, Theradex, Tvardi Therapeutics, Incorporated, AIM ImmunoTech Inc., BioNTech SE, Prestige Biopharma Limited, HCW Biologics, Cantex Pharmaceuticals, XBiotech, Inc., Lumicell, Inc., CARsgen Therapeutics Co., Ltd., Panbela Therapeutics, Inc. , among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP

临床2期临床3期临床结果免疫疗法快速通道

2024-06-18

·GlobeNewswire-Health Care

Candel Therapeutics to Participate in the H.C. Wainwright 2nd Annual Immune Cell Engager Virtual Conference

NEEDHAM, Mass., June 18, 2024 (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 that Paul Peter Tak, MD, PhD, FMedSci, Candel’s President and Chief Executive Officer, will participate in a fireside chat at the H.C. Wainwright 2nd Annual Immune Cell Engager Virtual Conference on Tuesday, June 25, 2024 at 3:00 p.m. ET. A live webcast of the fireside chat will be available by selecting Events and Presentations under the News & Events tab in the Investors section on candeltx.com. A replay of the webcast will be archived for up to 90 days following the session date. 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 non-small cell lung cancer (NSCLC) (phase 2), borderline resectable pancreatic ductal adenocarcinoma (phase 2), and localized, non-metastatic prostate cancer (phase 2 and phase 3). The Company recently announced encouraging overall survival data for CAN-2409 in both pancreatic cancer and NSCLC. CAN-2409 received Fast Track Designation from the FDA for prostate cancer, pancreatic cancer, and NSCLC as well as Orphan Drug Designation in pancreatic cancer. Topline data are expected for both the phase 2b (active surveillance population) and the phase 3 (intermediate-to-high-risk prostate cancer) randomized, placebo-controlled clinical trials in localized prostate cancer in Q4 2024. 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). Clinical activity and biomarker data were published in Nature in October 2023. CAN-3110 received Fast Track Designation as well as Orphan Drug Designation from the FDA for recurrent high-grade glioma. The Company expects sharing further clinical updates in the second half of 2024. Finally, Candel’s enLIGHTEN™ Discovery Platform is a systematic, HSV-based discovery platform leveraging human biology and advanced analytics to create new viral immunotherapies for solid tumors. During the Society for Immunotherapy of Cancer (SITC) 2023 Annual Meeting, the Company presented encouraging data on the first immunotherapy candidate from this platform, Alpha 201-macro-1, which was designed to interfere with the CD47/SIRP1α pathway, in mouse models of breast cancer and lung cancer. During the American Association for Cancer Research (AACR) Annual Meeting in April 2024, the Company presented preclinical data on its immunotherapy candidate for induction of tertiary lymphoid structures (TLS), being developed as a novel therapeutic strategy for solid tumors, its second candidate from the enLIGHTEN™ Discovery Platform. For more information about Candel, visit: 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 development programs, including expectations regarding the therapeutic benefit of the Company’s programs, the ability of the Company’s programs to extend patient survival; and expectations regarding the potential benefits conferred by the Company’s inclusion in the broad-market Russell 3000 Index. 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; the Company’s ability to continue as a going concern; expectations regarding the therapeutics 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 JenkinsVP, Investor Relations and Business DevelopmentCandel Therapeutics, Inc.tjenkins@candeltx.com Media Contact:Kyle EvansICR WestwickeCandelPR@westwicke.com

快速通道免疫疗法临床2期临床1期孤儿药

2024-06-13

·CPHI制药在线

浅谈胰腺导管癌治疗进展：在研药物多样，诺华放弃，康宁杰瑞惨败

关注并星标CPHI制药在线胰腺癌是一组主要起源于胰腺导管上皮及腺泡细胞的恶性肿瘤，恶性程度极高，起病隐匿，早期诊断困难，进展迅速，生存时间短，是预后最差的恶性肿瘤之一，被称为"癌中之王"。即使在新疗法不断涌现的今天，胰腺癌的治疗也并未取得突破进展。下面笔者将浅谈下胰腺癌的主要类型--胰腺导管腺癌的治疗现状，以及近年该领域药物的研究进展。关于胰腺导管癌胰腺导管腺癌（PDAC）是一种发生于胰腺导管上皮的肿瘤，是胰腺癌中的主要类型，约占90%以上。PDAC起病隐匿，且具有高度侵袭性，大多患者确诊时已处于晚期。由于缺乏有效的治疗手段，PDAC患者总体5年生存率< 12 %。据2024年2月中国国家癌症中心（NCC）发布的2022年中国新发癌症病例数和死亡人数数据：2022年中国胰腺癌新发病例11.87万，死亡人数10.63万。手术和化疗是PDAC的主要治疗手段，但只有15%-20%的患者在诊断时符合手术条件。不过据《Nature》官网发布的相关研究论文数据，即便能手术，近90% 的PDAC患者在治疗平均7~9个月内会面临复发。而晚期PDAC标准治疗是化疗，常采用联合治疗方案，如AG（白蛋白紫杉醇联合吉西他滨）方案、改良FOLFIRINOX（mFOLFIRINOX，奥沙利铂+伊立替康+亚叶酸钙+氟尿嘧啶）方案或S-IROX（替吉奥+伊立替康+奥沙利铂）方案。据2023年6月美国国家综合癌症网络（NCCN）指南发表的2023年第2版胰腺癌诊治指南：（1）对于部分可切除性胰腺癌，指南推荐先行新辅助治疗（NAT）再手术，推荐方案包括FOLFIRINOX或改良FOLFIRINOX方案，以及吉西他滨联合白蛋白结合紫杉醇方案（AG方案），其中FOLFIRINOX或mFOLFIRINOX方案适用于美国东部肿瘤协作组（ECOG）评分0~1分的病人。术后指南建议患者常规开展化疗，化疗首选方案包括FOLFIRINOX/mFOLFIRINOX方案或吉西他滨联合卡培他滨方案；（2）对于晚期或转移性胰腺癌：PS评分良好（0~1分）局部晚期/转移性胰腺癌一线治疗新增NALIRIFOX方案，即脂质体伊立替康+5-氟尿嘧啶+亚叶酸+奥沙利铂，PS评分中等（2分）局部晚期胰腺癌一线治疗首选卡培他滨或吉西他滨单药化疗或AG方案，PS评分中等（2分）转移性胰腺癌首选AG方案，其次卡培他滨或吉西他滨，NALIRIFOX方案在某些情况下也可使用；（3）对于复发的局部进展期/转移性胰腺癌，PS评分良好者，当NTRK融合基因阳性，首选恩曲替尼或拉罗替尼；当存在微卫星高度不稳定（MSI-H）、错配修复缺陷（dMMR）或肿瘤突变负荷（TMB）≥10 mut/Mb者，建议使用帕博丽珠单抗。新版指南建议在其他治疗方案中新增以下内容：对于合并MSI-H、dMMR者，可使用多塔利单抗；若TMB≥10 mut/Mb，也可使用纳武利尤单抗+伊匹木单抗；PS评分中等者，无首选方案。胰腺导管癌药物研究进展上述方案对PDAC治疗效果有限，且有些药物只适用于特定患者。药企对PDAC新疗法的探索从未止步，今年2月FDA批准NALIRIFOX（脂质体伊立替康 (Onivyde)+奥沙利铂+氟尿嘧啶 (5-FU)/亚叶酸）方案一线治疗转移性PDAC。此外，目前全球还有多款在研PDAC新疗法，详见下表。这些在研疗法作用靶点各异，具体适应症有所不同，且药物类型多样，涉及化药、单抗、双抗、CAR-T疗法、疫苗以及溶瘤病毒等。研发进度上，NIS793、KN046等处于3期临床。其中NIS793是一种完全人源的单克隆抗体，通过阻断TGFβ细胞因子而发挥作用，2021年被FDA授予治疗胰腺癌的孤儿药资格，其联合吉西他滨和Nab-紫杉醇一线治疗PDAC的临床试验已进入3期阶段。值得一提的是，诺华曾于2015年从Xoma引进NIS793，但2024年诺华宣布停止研发NIS793，并将其退还给Xoma。 KN046是康宁杰瑞研发的一款PD-L1/CTLA-4靶向双抗。已公布的2期临床研究（NCT04324307）数据显示：对于31例无法切除的晚期胰腺癌患者，KN046联合AG方案的ORR为45.2%，DCR为93.5%。遗憾的是，今年5月，康宁杰瑞宣布KN046联合AG方案一线治疗不可切除局部晚期或转移性PDAC的3期临床试验KN046-303惨遭失败，OS结果未达到统计学终点。索凡替尼治疗胰腺癌方面处于2/3期临床，2024年5月其联合卡瑞利珠单抗和化疗（白蛋白结合型紫杉醇+吉西他滨)一线治疗转移性PDAC的2/3期临床试验启动。该药是和黄医药开发的一种新型的口服酪氨酸激酶抑制剂，已被NMPA批准用于无法手术切除的局部晚期或转移性、进展期非功能性、分化良好（G1、G2）的非胰腺（2020年12月）和胰腺（2021年6月）来源的神经内分泌瘤。已公布的索凡替尼治疗胰腺癌的临床试验结果显示：索凡替尼联合TAS-102三线或后线治疗方案对mPDAC患者有令人鼓舞的抗肿瘤活性，特别是对无肝转移患者。此外，与索凡替尼仅联合化疗相比，索凡替尼联合卡瑞利珠单抗和化疗一线治疗胰腺癌可显著延长患者的OS和PFS。 CAN-2409、Motixafortide等处于2期临床。其中CAN-2409是一种复制缺陷的腺病毒，旨将单纯疱疹病毒胸苷激酶（HSV-tk）基因递送至患者的肿瘤并诱导个体化的全身抗肿瘤免疫反应。HSV-tk是一种酶，可局部将口服伐昔洛韦转化为杀死附近癌细胞的有毒代谢物，从而释放多种癌症抗原。该疗法通过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。2024年4月，CAN-2409被FDA授予治疗胰腺癌的孤儿药资格。已公布的CAN-2409联合抗病毒药物与标准护理（SoC）放化疗用作可切除PDAC术前辅助治疗的2期临床试验结果显示：截至2024年3月29日数据，在边缘性可切除PDAC中，CAN-2409组患者的mOS为28.8个月（Vs 对照组的12.5个月）；24个月时，CAN-2409治疗组患者的生存率为71.4%（Vs 对照组的16.7%），；36个月时，CAN-2409治疗组的生存率为47.6%（Vs 对照组的16.7%）。CAN-2409还显示出良好的耐受性，没有显著的额外局部或全身毒性。而且，对切除肿瘤的分析显示，患者在使用CAN-2409联合疗法后，其PDAC组织中出现密集的免疫细胞聚集，包括CD8+细胞、细胞毒性肿瘤浸润淋巴细胞和树突状细胞，这证实该疗法能够激活强大的抗肿瘤免疫反应。安全性方面，在SoC中添加CAN-2409方案显示出良好的耐受性，没有观察到剂量限制性毒性。 Motixafortide是Biokine Therapeutics 研发的一款靶向CXCR4的长效合成多肽拮抗剂，后授权给BioLineRx。2023年9月，该疗法被FDA批准联合filgrastim（G-CSF），以在多发性骨髓瘤患者中动员造血干细胞到外周血进行采集，辅助进行自体干细胞移植。治疗PDAC方面，已公布的临床研究结果显示：Motixafortide联合帕博利珠单抗和化疗在治疗PDAC方面表现出良好的安全性和耐受性，且在预后不良和病情凶险的PDAC人群中显示出疗效。 2023 AACR上公布的Motixafortide联合帕博利珠单抗和AG方案一线治疗转移性胰腺癌的单臂2期临床试验结果显示：可评估患者(11人)的ORR为55%，36%患者出现PR，1例患者的肝转移病灶得到缓解。此外，27%的患者(3例)病情稳定，DCR为82%。 Mitazalimab是一种靶向CD40的单克隆抗体，通过激活树突状细胞、B细胞和巨噬细胞等免疫细胞，使肿瘤对化疗敏感，大幅增强抗肿瘤的能力。今年2月，该药被欧盟授予孤儿药资格，联合与mFOLFIRINOX方案一线治疗转移性PDAC。 2024年1月，Alligator Bioscience宣布Mitazalimab联合mFOLFIRINOX化疗一线治疗胰腺癌的2期临床研究达到主要研究终点。具体数据为：57名可评估患者的ORR为40.4%，DCR为79%，mOS为14.3个月，中位缓解持续时间为12.5个月（优于FOLFIRINOX标准治疗的5.9个月）。 CEND-1是一种由9个氨基酸构成的环肽药物，可与肿瘤中选择性表达的alpha-v整合素结合，然后被肿瘤微环境中表达的蛋白酶切割，释放出被称为CendR片段的肽片段，该片段再与第2个受体neuropilin-1结合，从而激活一种新的摄取途径（CendR途径），使抗癌药物能够穿透实体瘤。CEND-1改变肿瘤微环境以增强联合治疗药物的递送和功效的能力已在一系列实体瘤模型中得到证实。2021年2月，齐鲁制药与Cend Therapeutics签订合作和许可协议，获得CEND-1在大中华区开发和商业化权益。柳叶刀杂志上发表的CEND-1联合标准治疗化疗（吉西他滨和白蛋白紫杉醇）一线治疗转移性PDAC的1期临床研究数据显示：29例疗效可评估患者中的ORR为59%，mOS为13.2个月。 Efineptakin Alfa治疗胰腺癌方面处于1/2期临床。该药是一种长效人类白细胞介素 7，其联合帕博利珠单抗对胰腺癌患者展示出良好的疗效：7.7％的患者肿瘤大幅缩小或消失，34.6％的患者疾病得到有效控制。2024年2月，该疗法被FDA授予治疗晚期胰腺癌的孤儿药资格。 ELI-002、D-1553等处于1期临床。其中ELI-002是一款针对KRAS突变的治疗型疫苗，主要针对KRAS突变阳性实体瘤，尤其是PDAC、结直肠癌。该疫苗由两个关键组件构成，即AMP-CpG（一种特有的免疫激活剂，可刺激免疫系统产生强烈的反应）和AMP-mKRAS-肽。其中AMP-mKRAS-肽是一种经修饰的KRAS突变肽，可特异性地引导机体免疫系统，追踪并摧毁携带KRAS突变的癌细胞。 2024年1月《Nature》杂志上发表的1期临床试验AMPLIFY-201结果显示：ELI-002可显著降低患者肿瘤标志物水平，并产生强烈的T细胞应答，从而降低患者复发及死亡的风险，且总体上被认为是安全可控的。 IBI389是信达生物自主研发的一种抗CLDN18.2/CD3双特异性抗体。2024 ASCO上公布的IBI389治疗晚期不可手术或转移性PDAC的1期临床数据显示：600μg/kg治疗组疗效更佳，在27例至少进行了一次基线后肿瘤评估的受试者中，ORR为29.6% ，确认的客观缓解率（cORR）为25.9%，DCR达70.4%（95%CI：49.8-86.2）。在CLDN18.2 IHC 2/3+≥40%的18例受试者中，cORR达38.9%。此外，截至2024年5月1日，中位随访时间为4个月，mPFS尚未成熟，3个月的PFS率达57.1%。 CT041是一种潜在全球同类首创、靶向CLDN18.2蛋白的自体CAR-T细胞疗法，用于治疗Claudin18.2阳性实体瘤，主要治疗胃癌/食管胃结合部腺癌及胰腺癌。最近公布的CT041治疗难治性转移性胰腺癌的两项多中心、开放标签的1/1b期临床试验数据显示：24例患者中有12例观察到肿瘤靶病灶不同程度缩小，ORR为16.7%，DCR为70.8%，临床获益率为37.5%。mDoR为9.5个月，12个月的DoR率为50%，mPFS为3.3个月，mOS为10.0个月，12个月时OS率为45.8%。 D-1553是益方生物自主开发的一款新型、高效、口服KRAS G12C抑制剂。已公布的D-1553针对KRAS G12C突变晚期胰腺癌的早期临床试验结果显示：D-1553单药治疗在KRAS G12C突变胰腺癌患者中展现出良好的耐受性和临床活性，确认的ORR为35.7%（5/14），DCR为85.7%（12/14），mPFS为8.54个月。今年5月，该药被CDE纳入突破性治疗品种，用于治疗经一线治疗失败的伴KRAS G12C突变局部晚期或转移性PDAC。 IMM-1-104是Immuneering 开发一款高选择性第三代小分子MEK抑制剂，每日口服一次。该药通过深度循环抑制MAPK途径，实现对RAS基因的通用抑制活性。在一项1/2a期研究中，IMM-1-104对包括PDAC、恶性黑色素瘤、NSCLC在内的多种实体瘤展现出良好的初步疗效。2024年2月，该药被FDA授予一线治疗PDAC的快速通道认定。总结整体来看，多款在研PDAC新疗法进入临床试验，且早期临床试验结果积极。监管机构也通过授予突破性疗法、快速通道资格等方式加速PDAC的研发进程。但PDAC的治疗较其他恶性肿瘤，如NSCLC、黑色素瘤，并未取得很大突破。而且，与其他恶性肿瘤在研药物不同，在研PDAC药物作用靶点相当分散，笔者分析这可能与PDAC自身的特性，以及诊断上缺乏特异的生物标志物有关。期待在研究人员的不懈努力下，PDAC治疗可以早日迎来新局面。【企业推荐】【智药研习社直播预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

上市批准

100 项与 Aglatimagene besadenovec 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15074

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
局限性前列腺癌	临床3期	美国	Candel Therapeutics, Inc.	2011-09-01
局限性前列腺癌	临床3期	波多黎各	Candel Therapeutics, Inc.	2011-09-01
非小细胞肺癌	临床2期	美国	Candel Therapeutics, Inc.	2020-10-13
前列腺癌	临床2期	墨西哥	Candel Therapeutics, Inc.	2016-05-01
胰腺腺癌	临床2期	美国	Candel Therapeutics, Inc.	2015-10-01
胰腺腺癌	临床2期	墨西哥	Candel Therapeutics, Inc.	2015-10-01
多形性胶质母细胞瘤	临床2期	美国	Candel Therapeutics, Inc.	2007-03-01
脑恶性胶质瘤	临床2期	美国	Candel Therapeutics, Inc.	2007-03-01
乳腺癌	临床1期	美国	Candel Therapeutics, Inc.	2013-10-01
恶性胸腔积液	临床1期	美国	Candel Therapeutics, Inc.	2013-10-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04495153 (ASCO2024) 人工标引	临床2期	非小细胞肺癌	73	CAN-2409 + valacyclovir	鹽餘鏇窪選獵構醖醖壓(築遞齋獵築鏇餘顧選簾) = 齋衊選衊築淵繭廠鬱壓遞獵膚鏇製窪壓築繭範 (願齋鬱淵醖構繭艱簾鑰, 14.3-NA) 更多	积极	2024-05-24
				CAN-2409 + valacyclovir (C1, stable disease)	鹽餘鏇窪選獵構醖醖壓(築遞齋獵築鏇餘顧選簾) = 憲範網遞獵範製繭積製遞獵膚鏇製窪壓築繭範 (願齋鬱淵醖構繭艱簾鑰 )
NCT02446093 (PaTK02, Biospace) 人工标引	临床2期	胰腺癌	13	CAN-2409+valacylovir or acyclovir+chemoradiation or SBRT	製夢憲糧蓋蓋鬱選鬱鬱(壓築範鬱夢膚夢構獵觸) = none 膚憲獵繭衊選願齋艱願 (鹽遞獵淵壓構鏇鑰鬱糧 )	积极	2024-04-04
				chemoradiation or SBRT
NCT00589875 (CTgov)	临床2期	多形性胶质母细胞瘤 \| 脑恶性胶质瘤	52	Radiation therapy+Temozolomide+Valacyclovir+CAN-2409	觸壓遞廠壓積餘糧鏇鹽(衊醖製膚觸選願壓鹽築) = 範齋鏇廠鏇鏇糧構憲觸顧製鏇蓋鏇壓窪夢觸構 (憲製蓋範齋鹽窪餘獵鑰, 簾願製顧製艱選觸顧膚 ~ 餘繭積衊範積鏇製簾膚) 更多	-	2024-04-03
NCT04495153 (Corporate Publications) 人工标引	临床2期	非小细胞肺癌二线	40	CAN-2409+valacyclovir+immune checkpoint inhibitor	鏇製鹽餘遞糧齋壓鹹繭(鬱夢選窪願窪鏇艱夢窪) = 壓簾鏇襯鹹壓齋糧鑰鏇製鏇壓蓋窪觸窪願獵構 (鑰淵鹹夢鹹夢鏇鑰醖繭 ) 更多	积极	2023-09-26
NCT03576612 (SITC2022) 人工标引	临床1期	高级别胶质瘤一线	41	valacyclovir+CAN-2409+nivolumab (patients with methylated MGMT promoter undergoing gross total resection (GTR))	憲壓廠衊糧網憲網艱糧(網遞積衊獵窪衊積遞鬱) = 鹹窪糧顧簾艱鏇獵築衊鬱窪鹹壓糧衊艱鑰繭願 (夢衊繭簾簾積壓選淵膚 )	积极	2022-11-01
				valacyclovir+CAN-2409+nivolumab (patients with methylated MGMT promoter undergoing sub-total resection (STR))	憲壓廠衊糧網憲網艱糧(網遞積衊獵窪衊積遞鬱) = 鬱製鹹製蓋鹽獵憲製醖鬱窪鹹壓糧衊艱鑰繭願 (夢衊繭簾簾積壓選淵膚 )
NCT04495153 (ASCO2022) 人工标引	临床2期	非小细胞肺癌	28	ICI+Aglatimagene besadenovec (stable disease)	顧鑰襯積鏇願選襯築鏇(遞淵憲糧糧構鏇窪衊鏇) = Of the 14 RECIST evaluable patients who received 2 doses of CAN-2409, clinical response was seen in 4 patients 選獵鬱獵鏇獵醖鹹襯鑰 (壓鹹簾築築鹽鬱壓壓築 ) 更多	积极	2022-06-02
				ICI+Aglatimagene besadenovec (progressive disease after ≥18 weeks)
NCT03004183 (ASCO2021) 人工标引	临床2期	转移性非小细胞肺癌	35	ADV/HSV-tk+pembrolizumab or nivolumab (ICI-naïve)	構蓋觸願糧鹽鹽夢鬱獵(簾網築糧築繭襯淵願鹹) = 範膚選壓襯鬱壓鹽壓築鏇鑰衊顧鬱鑰觸蓋鹽顧 (鏇襯鹹願蓋範鏇積齋構 ) 更多	积极	2021-05-20
				ADV/HSV-tk+pembrolizumab or nivolumab (Previous ICI)	構蓋觸願糧鹽鹽夢鬱獵(簾網築糧築繭襯淵願鹹) = 築觸憲觸淵鏇鏇艱繭製鏇鑰衊顧鬱鑰觸蓋鹽顧 (鏇襯鹹願蓋範鏇積齋構 ) 更多
NCT03131037 (ASCO2020) 人工标引	临床1期	非小细胞肺癌新辅助	12	Valacyclovir+aglatimagene besadenovec	壓糧鏇憲淵醖淵簾夢夢(製繭鏇製膚淵廠構獵製) = CTC grade 1 fever (n = 1), flu-like symptoms (n = 1) and nausea/vomiting/diarrhea (n = 1). The only > grade 2 lab abnormality was transient grade 3 lymphopenia (n = 2) 範鏇齋獵淵製蓋窪膚構 (製簾鑰獵願範觸膚餘積 )	积极	2020-05-29
NCT00634231 (Pubmed \| Neuro Oncol) 人工标引	临床1期	室管膜瘤 \| 脑恶性胶质瘤	8	valacyclovir+chemotherapy+AdV-tk	築衊襯構簾範獵鏇構壓(夢願構觸觸憲構製鏇廠) = 鏇糧鬱衊餘糧糧窪築製窪遞鹽膚夢積窪鑰壓獵 (網廠鹹範構衊餘憲築壓 )	积极	2019-03-18
NCT00870181 (Pubmed)	临床2期	复发性恶性胶质瘤	53	Adenovirus-mediated delivery of herpes simplex virus thymidine kinase (ADV-TK)	製顧鹹蓋製繭鹹範獵窪(餘餘廠積繭觸廠憲簾觸) = 淵範淵夢鏇觸繭廠構選遞糧壓膚艱齋願網壓簾 (夢鑰膚鏇築觸構鑰餘艱 ) 更多	积极	2016-01-26