This is a single-arm pilot feasibility study evaluating the combination of Botensilimab and Balstilimab with Radiation Therapy (RT) in Non-Microsatellite Instability High (MSI-H) or Proficient Mismatch Repair (pMMR) chemorefractory colorectal cancer (CRC) with liver metastasis.

开始日期2026-01-01

申办/合作机构

The Massachusetts General Hospital

[+1]

NCT07152821

/ Not yet recruiting临床3期IIT

Botensilimab + Balstilimab vs Best Supportive Care as Therapy in Chemo-refractory, Unresectable, Colorectal Adenocarcinoma: The BATTMAN Trial

This study is being done to answer the main question of: Do patients with colorectal cancer that cannot be removed by surgery, that is treated with two new immunotherapy drugs, botensilimab and balstilimab, live longer? Other important questions include: Is their quality of life better? Do their tumours slow in growth or possibly shrink in size? Are there markers in their tumour or blood that can predict whether they achieve any of these benefits? In addition, the study is done to confirm the safety of these immunotherapy drugs and to determine how long it takes for the body to metabolize them.

开始日期2025-11-30

申办/合作机构

Canadian Cancer Trials Group

[+2]

NCT06843551

/ Recruiting临床2期IIT

A Phase 2 Single Arm Trial of Stereotactic Body Radiation Therapy Followed by Dual Immune Checkpoint Inhibition for Patients With Metastatic Pancreatic Ductal Adenocarcinoma - The Miami "EMPIRE" Trial - Eradication of Metastatic Pancreatic Cancer With Immuno-Radiation

The purpose of this study is to assess if radiation therapy (which uses high-energy radiation to damage or destroy cancer cells) combined with immune checkpoint inhibitors (medications that helps the body recognize and attack cancer cells) will be beneficial for patients with metastatic pancreatic ductal adenocarcinoma.

开始日期2025-06-18

申办/合作机构

University of Miami

[+1]

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100 项与巴替利单抗相关的转化医学

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100 项与巴替利单抗相关的专利（医药）

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187

项与巴替利单抗相关的文献（医药）

2025-04-10·JOURNAL OF CLINICAL ONCOLOGY

Botensilimab (Fc-enhanced anti–cytotoxic lymphocyte-association protein-4 antibody) Plus Balstilimab (anti–PD-1 antibody) in Patients With Relapsed/Refractory Metastatic Sarcomas

Article

作者: Schwartz, Gary K. ; Jones, Robin L. ; Bullock, Andrea J. ; Grossman, Joseph E. ; Trent, Jonathan C. ; Avagyan, Manushak ; O'Day, Steven ; Johnson, Benny ; Agulnik, Mark ; Chand, Dhan ; Henick, Brian ; Delepine, Chloe ; Singh, Arun ; Gordon, Michael S. ; El-Khoueiry, Anthony B. ; Wu, Wei ; Stebbing, Justin ; Mahadevan, Daruka ; Wilky, Breelyn A. ; Tsimberidou, Apostolia M.

PURPOSE:

Outcomes for patients with advanced sarcomas are poor and there is a high unmet need to develop novel therapies. The purpose of this phase I study was to define the safety and efficacy of botensilimab (BOT), an Fc-enhanced anti–cytotoxic lymphocyte-association protein-4 antibody, plus balstilimab (BAL), an anti–PD-1 antibody, in advanced sarcomas.

METHODS:

BOT was administered intravenously (IV) at 1 mg/kg or 2 mg/kg once every 6 weeks in combination with BAL IV at 3 mg/kg once every 2 weeks for up to 2 years. The primary end point was to determine dose-limiting toxicities during the dose-escalation period. Secondary end points include objective response rate (ORR), duration of response (DOR), disease control rate, and progression-free survival (PFS) by RECIST 1.1. Exploratory end points include assessing patient biomarkers including tumor mutational burden, cytokines, and PD-L1 expression.

RESULTS:

Overall, 64 patients with sarcoma were treated; all were evaluable for safety and 52 for efficacy. The most common treatment-related adverse event (TRAE) was diarrhea/colitis occurring in 35.9% of patients, with grade 3 in 6.3% of patients. No grade 4 or 5 TRAEs were reported. For all evaluable patients, ORR was 19.2% (95% CI, 9.6 to 32.5), and 27.8% (95% CI, 9.7 to 53.5) for evaluable patients with angiosarcoma (n = 18); 33.3% in visceral and 22.2% in cutaneous subtypes. Median PFS for evaluable patients was 4.4 months (95% CI, 2.8 to 6.1), with a 6-month PFS rate of 36% (95% CI, 22 to 50) and a median DOR of 21.7 months (95% CI, 1.9 to not reached).

CONCLUSION:

The combination of BOT/BAL demonstrated promising efficacy and safety in a large cohort of heavily pretreated sarcoma patients. This encouraging activity warrants further investigation (ClinicalTrials.gov identifier: NCT03860272 ).

2025-02-17·CLINICAL CANCER RESEARCH

The Prostaglandin EP4 Antagonist Vorbipiprant Combined with PD-1 Blockade for Refractory Microsatellite-Stable Metastatic Colorectal Cancer: A Phase Ib/IIa Trial

Article

作者: Niger, Monica ; Cristarella, Eleonora ; Vitalini, Cristina ; Rovati, Lucio C. ; Chiodoni, Claudia ; Morano, Federica ; Brambilla, Nadia ; Zaffaroni, Nadia ; Doldi, Valentina ; Girolami, Federica ; Ghelardi, Filippo ; Giacovelli, Giampaolo ; Pietrantonio, Filippo ; Benincasa, Elena ; Palazzo, Michele ; Nichetti, Federico ; Sabella, Giovanna ; Manca, Paolo

Abstract:

Purpose::

Novel combinations are required to overcome resistance to immune checkpoint inhibitors in proficient mismatch repair (pMMR) or microsatellite-stable (MSS) metastatic colorectal cancer (mCRC). We aimed to determine whether vorbipiprant, a prostaglandin E2 receptor EP4 subtype antagonist, can convert immune-resistant mCRC into a tumor responsive to anti–PD-1 inhibition.

Patients and Methods::

This phase Ib/IIa prospective, open-label, single-arm trial followed a 3 + 3 dose-escalation and dose-optimization design. A total of 28 patients with chemorefractory pMMR/MSS mCRC were given dose-escalated oral vorbipiprant (30, 90, or 180 mg twice daily), along with biweekly intravenous balstilimab (3 mg/kg), an anti–PD-1 antibody. The primary endpoints included safety and the disease control rate (DCR). Secondary endpoints were the overall response rate, duration of response, progression-free survival, and overall survival.

Results::

No dose-limiting toxicities were observed. Of the 28 patients, seven (25%) experienced serious adverse events, but only one was attributed to vorbipiprant and one to balstilimab. The trial achieved a DCR of 50% observed across the entire cohort. In the subgroup of patients with liver metastases (n = 12), the DCR was 25%. The overall response rate was 11%, with three patients showing a partial response (median duration of response, 7.4 months). The median progression-free survival was 2.6 months, and the median overall survival was 14.2 months. Translational exploratory analyses suggested that vorbipiprant may boost response to anti–PD-1 in patients with immunogenic tumors.

Conclusions::

The combination of vorbipiprant and a PD-1 inhibitor (balstilimab) yielded sufficient activity in refractory pMMR/MSS mCRC, which is worthy of confirmation in future clinical trials in biomarker-enriched populations.

2025-02-01·JOURNAL OF ETHNOPHARMACOLOGY

Synergistic effects of Lianhuaqingwen in combination with Oseltamivir and Baloxavir against seasonal influenza virus: In vitro and in vivo assessment

Article

作者: Duan, Xuefeng ; Li, Xuanxuan ; Du, Han ; Bi, Yuhai ; Zhang, Cheng ; Yang, Jing ; Qi, Hui ; Rong, Wenwan ; Ma, Zhenghai ; Yuan, Manhua ; Li, Jianxiong ; Ji, Tiannan ; Zhang, Ning ; Dai, Bo

ETHNOPHARMACOLOGICAL RELEVANCE:

Lianhuaqingwen (LH), a traditional Chinese medicine, presents a broad-spectrum antiviral effect and has been widely used to treat influenza. Given the potential rise of drug-resistant influenza viruses, it is necessary to develop new antiviral drugs and explore combination therapies involving LH in tandem with existing antivirals such as Oseltamivir acid (Osel) or Baloxavir (Bal). These multidrug combinations could help effectively control the seasonal influenza epidemics and reduce the disease burden.

AIM OF THE STUDY:

This study aimed to evaluate the antiviral effects of LH, alone and in combination with Osel or Bal, against human seasonal influenza viruses in vitro and in vivo models.

MATERIALS AND METHODS:

The antiviral efficacy of LH alone and LH in combination with Osel/Bal against seasonal influenza A viruses (IAVs) (H1N1 and H3N2 subtypes) and influenza B viruses (IBVs) (BV- and BY-lineages) was assessed in vitro using MDCK cells. The median effective concentration (EC₅₀) was determined, and the drug synergies were analyzed. Additionally, the antiviral activity of LH monotherapy and LH + Osel/Bal combination therapy were evaluated in vivo using an H1N1-infected BABL/c mouse model by monitoring changes in body weight, survival rate, lung viral titer, pathological damage, and inflammatory reaction.

RESULTS:

In vitro, LH alone and in combination with Osel/Bal exhibited antiviral activity against both IAVs and IBVs. The addition of LH to Osel/Bal improved the therapeutic efficacy compared to Osel/Bal alone. In vivo, LH monotherapy reduced body weight loss and increased the survival rates of H1N1-infected mice. LH in combination with Osel/Bal resulted in lower virus titers, more effective relief of pathological damage, and comparable low expression of inflammatory factors in the lungs of H1N1-infected mice compared to the use of Osel/Bal alone. Transcriptomic analysis of the lungs revealed that LH + Osel/Bal significantly increased the expression of genes associated with antiviral and anti-inflammatory effects.

CONCLUSIONS:

This study evaluated the antiviral effects of LH monotherapy and combination therapy with Osel/Bal against human seasonal influenza viruses in vitro and in vivo models. The results suggest that combining LH with Osel or Bal could enhance the antiviral efficiency for influenza viruses compared to the monotherapy using any of these three drugs.

191

项与巴替利单抗相关的新闻（医药）

2025-10-17

·Business Wire

Agenus Reports 39% of Patients Alive at Two-Years with BOT/BAL Across Multiple Refractory Solid Tumors at ESMO 2025

LEXINGTON, Mass.--(BUSINESS WIRE)--Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology innovation, today announced new data from its botensilimab (BOT), a multifunctional, Fc-enhanced CTLA-4 antibody and balstilimab (BAL), a PD-1 inhibitor, combination demonstrating durable survival across multiple cancer types in late-stage patients who have limited treatment options. The results, featured in an oral session at the European Society for Medical Oncology (ESMO) Congress 2025 in Berlin, Germany presented by Dr. Michael Gordon of HonorHealth Research Institute, include emerging two-year survival plateaus indicating a strong clinical signal that BOT/BAL’s benefit may be agnostic to tumor type. “We are seeing consistent signals that this combination can convert ‘cold,’ IO resistant tumors into responsive ones, not only in late-line settings but potentially in earlier lines where immunotherapy may deliver even greater benefit." “With longer follow up, we’re finding that approximately 40% of patients with very limited survival expectation are alive at two years,” said Michael S. Gordon, MD, HonorHealth Research Institute. “These results are in patients with cancers that historically have been resistant to earlier immunotherapy approaches or have progressed following prior immunotherapy treatment, and they support advancing randomized trials like the phase 3 BATTMAN trial to create an immunotherapy option for patients who have historically had none." Highlights from the Oral Presentation (Abstract #1517MO): New data from expansion cohorts of 411 patients (339 evaluable for efficacy) enrolled in the Phase 1b C-800-01 study evaluating BOT/BAL in patients with advanced, refractory disease across more than 5 cancer types. 61% of patients enrolled received three or more prior lines of therapy Objective response rates (ORR): 17% across both BOT 1 mg/kg and 2 mg/kg doses Signals of benefit across tumor types, including those historically unresponsive to immunotherapy, had prior treatment with checkpoint inhibitors, and/or with active liver metastases. 2-year median overall survival (OS): 39% Median OS (mOS): 17.2 months Combination was well tolerated with most immune‑related side effects were reversible and gastrointestinal in nature; no treatment‑related deaths occurred Immune activation correlated with improved survival These findings build on previously reported 2-year overall survival of 42% and median OS of 20.9 months with BOT/BAL in refractory MSS mCRC with non-liver metastasesi and complement emerging data in the neoadjuvant setting, where BOT/BAL has also shown activity across multiple tumor typesii, further underscoring the platform potential of Agenus’ next-generation Fc-enhanced CTLA-4. In a further validation of its clinical impact, the French National Authority for Health (HAS) recently authorized BOT in combination with BAL under France’s Compassionate Access (AAC) early access program. This marks the first government-funded access pathway in France, for patients with refractory microsatellite‑stable (MSS) metastatic colorectal cancer (mCRC) who have exhausted all available treatment options. “BOT/BAL’s immune activation profile is truly differentiated,” said Steven J. O’Day, MD, Chief Medical Officer, Agenus. “We are seeing consistent signals that this combination can convert ‘cold,’ IO‑resistant tumors into responsive ones, not only in late-line settings but potentially in earlier lines where immunotherapy may deliver even greater benefit.” Broader Presence at ESMO 2025 In addition to the pan-tumor dataset, three additional posters will be presented highlighting clinical activity across hard-to-treat cancers: Cervical cancer: Results from the global Phase 2 RaPiDs trial (Abstract #2952) MSS mCRC: A Phase 1 trial of BOT/BAL + regorafenib (Abstract #6197) Non-melanoma skin cancer: Data from the AGENONMELA study (Abstract #7273) These presentations further support the breadth and versatility of Agenus’ immunotherapy pipeline across diverse cancer types and clinical settings. About Agenus Agenus is a leading immuno-oncology company targeting cancer with a comprehensive pipeline of immunological agents. The company was founded in 1994 with a mission to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants. Agenus has robust end-to-end development capabilities, across commercial and clinical cGMP manufacturing facilities, research and discovery, and a global clinical operations footprint. Agenus is headquartered in Lexington, MA. For more information, visit www.agenusbio.com or @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels. About the C-800-01 Study C-800-01 (NCT03860272) is an ongoing, multicenter Phase 1b clinical trial evaluating botensilimab in combination with balstilimab across advanced solid tumors. The trial enrolled over 400 patients with refractory disease and included tumor types with limited or no responsiveness to prior checkpoint inhibitors. Endpoints included objective response rate (ORR), duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Agenus’ Commitment to Patient Access Agenus is dedicated to making investigational medicines available to patients with cancer at the appropriate time and in the correct manner. For more information, visit https://agenusbio.com/access-to-investigational-medicines-policy About Botensilimab (BOT) Botensilimab (BOT) is a human Fc enhanced multifunctional anti-CTLA-4 antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses. Approximately 1,200 patients have been treated with botensilimab and/or balstilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov. About Balstilimab (BAL) Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. It has been evaluated in more than 900 patients to date and has demonstrated clinical activity and a favorable tolerability profile in several tumor types. Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding its botensilimab and balstilimab programs, expected regulatory timelines and filings, and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Annual Report on Form 10-K for 2024, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. __________________________ i Schlechter BM, et al. Poster presented at the ESMO Gastrointestinal Cancers Congress 2025. Barcelona, Spain. 2025. Poster #8P ii Chalabi M, et al. Oral presentation at AACR 2025. Chicago, IL, USA. 2025. Abstract #CT130.

临床结果免疫疗法临床1期临床2期AACR会议

2025-10-15

·奇点网

破局之“法”！通过重构宫颈癌供血系统，法米替尼“一箭双雕”，既直接抗癌又协同增效免疫治疗

*仅供医学专业人士阅读参考我国晚期宫颈癌患者，终于迎来了一种新疗法。国家药品监督管理局（NMPA）正式批准法米替尼+卡瑞利珠单抗联合疗法上市，用于治疗既往经过含铂化疗、但未经过贝伐珠单抗治疗的复发/转移性宫颈癌患者[1]。此次获批基于2期临床研究SHR-1210-II-217的数据，从最新研究数据来看，法米替尼联合卡瑞利珠单抗治疗组对于未经过贝伐珠单抗治疗的患者的客观缓解率（ORR）达到44.6%；中位无进展生存期（mPFS）为6.4个月；中位总生存期（mOS）更是达到了创纪录的20.2个月[2]。 SHR-1210-II-217研究论文首页截图[2] 不难看出，这一联合治疗方案的数据刷新了我国宫颈癌二线治疗生存期的记录，为我国晚期宫颈癌患者带来长生存希望。要想搞清楚法米替尼联合卡瑞利珠单抗为何能取得如此优异的疗效，还得从宫颈癌的治疗史说起。 1981年，顺铂的引入是晚期宫颈癌治疗的第一个转折点[3]，但是患者的总生存期仍未达到1年[4]。三十三年后，抗血管生成药物将复发/转移性宫颈癌患者的mOS提升到17个月，将患者的死亡风险降低了29%[5]，化疗联合抗血管生成药物也成为首选一线治疗方案[6]。不过，绝大部分患者仍会复发，这些治疗后进展的患者，又面临无药可医的局面。2018年，虽然免疫检查点抑制剂获批复发/转移性宫颈癌的二线治疗[7]，但是单药疗效非常有限，即使联合其他药物ORR也只停留在0%-31.8%之间[8-11]。正是在这样的大背景下，抗血管生成的法米替尼联合PD-1抑制剂卡瑞利珠单抗这一方案就诞生了。法米替尼是一种新型多靶点受体酪氨酸激酶抑制剂（TKI），能够靶向VEGFR2、PDGFRβ和c-Kit等多个靶点。在介绍它的威力之前，我们先要回顾下肿瘤的血管生成，因为法米替尼发挥作用与血管生成密不可分。我们都知道，肿瘤代谢旺盛、增殖迅速，因此它对氧气和营养物质有极大的需求。早在十九世纪，科学家就观察到了肿瘤生长伴随着血管的增加[12]。直到1968年，科学家才首次证实肿瘤细胞确实能释放血管生成因子，促进肿瘤的生长[13,14]。因此，三年之后，哈佛医学院的Judah Folkman就提出了——开发血管生成抑制剂治疗癌症的创新想法[15]。在此之后，科学家找到了大量与肿瘤血管生成相关的信号通路，受体酪氨酸激酶c-Kit、VEGFR2和PDGFRβ就是其中的三个。 VEGF是调节肿瘤血管生成的典型细胞因子，它在与受体酪氨酸激酶VEGFR结合之后，会激活血管内皮细胞的生长和生存，以及血管生成相关的典型下游信号通路（如PI3K/AKT/mTOR等），进而促进血管的生成，以及肿瘤的生长和转移[16]。有研究表明，在病理性血管生成中，最关键的信号通路是VEGF-A/VEGFR2，它可以促进内皮细胞的分裂和形态发生，并诱导癌细胞的增殖、迁移、侵袭和瘤内血管生成[17]。在宫颈癌中，HPV病毒编码的致癌蛋白E6和E7，分别会导致抑癌蛋白p53的降解和pRb的失活，进而导致VEGF表达上调，从而驱动肿瘤血管生成[18]。我国西京医院团队的一项研究发现，81.0%的宫颈癌患者存在VEGFR2中/高水平表达；而且，VEGFR2高表达预示着OS较差[19]。因此，阻断VEGF/VEGFR信号通路，就有抑制宫颈癌进展的作用，抗VEGF抗体的成功，就是最好的证据。体外研究表明，法米替尼对VEGFR2有较强的抑制活性，IC50值为4.7nM[20]。 VEGFR2在宫颈癌中高表达且与OS密切相关[19] 虽然抗VEGF单抗取得了一些积极成果，但临床获益并未达到预期，患者的PFS率改善不大，OS率改善甚微，甚至在一些治疗失败的病例中，患者遭受的毒性反应药远远大于治疗效果[16]。正如前文所言，肿瘤的血管生成受多条通路控制，因此肿瘤可以通过其他通路逃避单一抗VEGF单抗的治疗作用。 PDGFR和它的配体PDGF，也在肿瘤血管生成中发挥重要作用。它们是血管生成过程中，募集周细胞的关键信号通路，对血管发育、稳定、成熟和重塑有至关重要的作用[21]。在这条信号通路中，被研究最多的当属PDGF-BB/PDGFRβ，它可以调控MAPK/ERK、PI3K/AKT和JNK等重要促癌通路，可促进癌细胞的增殖和转移[22]。此外，PDGFRβ还通过影响细胞与细胞外基质结构之间的张力，参与间质压力的调节[23]。要知道，由于不规则的血管生成导致肿瘤血管发育异常，大多数恶性肿瘤的间质压力都会升高，这给抗癌药物从血液循环中进入肿瘤造成了生理障碍[23]。已经有研究发现，52.7%的宫颈癌肿瘤细胞PDGFRβ呈阳性，62.5%的宫颈癌细胞系表达PDGFB[23]；而且，科学家已经发现，宫颈癌患者肿瘤组织的间质压力增加[24]。值得注意的是，有研究表明，特异性抑制PDGFRβ活性可显著降低PDGF-BB高表达肿瘤的生长和血管生成[25]。体外研究结果显示，法米替尼对PDGFRβ也有较强的抑制活性，IC50值为6.6nM[20]，远低于其他TKIs。 52.7%的肿瘤细胞中PDGFRβ呈阳性[23] 值得注意的是，来自瑞典卡罗林斯卡医学院的研究人员发现，同时抑制VEGF和PDGFR可以发挥协同作用：抑制PDGFRβ会阻断周细胞的募集，从而使血管暴露于VEGF抑制剂，进而抑制血管萌发并加剧肿瘤缺氧，达到更强的抑瘤作用[26]。除了能阻断VEGF和PDGFR通路之外，法米替尼还可以抑制受体酪氨酸激酶c-Kit的活性。在被配体干细胞因子（SCF）激活后，c-Kit可促进血管平滑肌细胞的生存并抑制凋亡，还可以激活促血管生成反应，增强内皮细胞的迁移能力和毛细血管的形成；而c-Kit缺失，则会阻碍血管内皮干细胞的增殖，并抑制体内血管生成[27]。一项来自中国的研究发现，在宫颈癌中，c-Kit的表达随宫颈癌分化程度降低而升高，这说明c-Kit与宫颈癌的侵袭能力有关[28]。法米替尼对c-Kit的抑制活性超强，IC50值仅为2.3nM[20]，是其他TKIs的数倍到数百倍。法米替尼对VEGFR2、PDGFRβ和c-Kit等与血管生成密切相关的受体酪氨酸激酶，有强效抑制能力，就是法米替尼联合卡瑞利珠单抗能刷新晚期宫颈癌二线治疗生存期纪录的关键原因之一。除了可以直接抗癌之外，近年来，科学家发现，抗血管生成药物其实可以平衡肿瘤微环境中的抗血管生成信号与促血管生成信号，进而促使肿瘤血管正常化，重塑肿瘤血管和免疫微环境，最终增效免疫检查点抑制剂的抗癌能力[29]。而抗血管药物法米替尼与免疫检查点抑制剂卡瑞利珠单抗的组合，恰好实现了上述的协同增效作用，这也是这一组合疗法表现优异的第二个重要原因。总的来说，由于对三种重要促血管生成受体酪氨酸激酶的强效抑制作用，让法米替尼不仅有直接抗肿瘤能力，还通过重塑肿瘤血管系统和免疫微环境，增强了免疫检查点抑制剂卡瑞利珠单抗的抗癌效果。在上述机制的加持下，这一联合治疗方案，进一步给患者带来了有临床意义的生存获益，而且没有增加新的不良反应谱。值得期待的是，在二线治疗取得成功的法米替尼+卡瑞利珠单抗没有止步，而是正在往一线治疗进发。目前，随机对照、开放标签、多中心III期临床研究SHR-1210-III-329正在积极推进中[30]，这个研究在探索这一组合疗法一线治疗复发/转移性宫颈癌的疗效和安全性。如果这一联合疗法在复发/转移性宫颈癌一线治疗中获得阳性结果，将会开启复发/转移性宫颈癌治疗的“去化疗”新时代。参考文献： [1].https://www.nmpa.gov.cn/zhuanti/cxylqx/cxypxx/20250529152509182.html [2].Xia L, Zhang K, Tang Y, et al. Camrelizumab Plus Famitinib versus Camrelizumab Alone and Investigator's Choice of Chemotherapy in Recurrent or Metastatic Cervical Cancer: A Randomized, Phase II Study. J Clin Oncol. 2025;43(24):2720-2733. doi:10.1200/JCO-24-02495 [3].Thigpen T, Shingleton H, Homesley H, Lagasse L, Blessing J. Cis-platinum in treatment of advanced or recurrent squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group. Cancer. 1981;48(4):899-903. doi:10.1002/1097-0142(19810815)48:4<899::aid-cncr2820480406>3.0.co;2-6 [4].Tomao F, Papa A, Rossi L, et al. Angiogenesis and antiangiogenic agents in cervical cancer. Onco Targets Ther. 2014;7:2237-2248. Published 2014 Dec 3. doi:10.2147/OTT.S68286 [5].Tewari KS, Sill MW, Long HJ 3rd, et al. Improved survival with bevacizumab in advanced cervical cancer [published correction appears in N Engl J Med. 2017 Aug 17;377(7):702. doi: 10.1056/NEJMx170002.]. N Engl J Med. 2014;370(8):734-743. doi:10.1056/NEJMoa1309748 [6].Abu-Rustum NR, Yashar CM, Arend R, et al. NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024. J Natl Compr Canc Netw. 2023;21(12):1224-1233. doi:10.6004/jnccn.2023.0062 [7].Marabelle A, Le DT, Ascierto PA, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2020;38(1):1-10. doi:10.1200/JCO.19.02105 [8].O'Malley D M, Oaknin A, Monk B J, et al. LBA34 Single-agent anti-PD-1 balstilimab or in combination with anti-CTLA-4 zalifrelimab for recurrent/metastatic (R/M) cervical cancer (CC): Preliminary results of two independent phase II trials[J]. Annals of Oncology, 2020, 31: S1164-S1165. doi:10.1016/j.annonc.2020.08.2264 [9].Naumann R W, Oaknin A, Meyer T, et al. Efficacy and safety of nivolumab (Nivo)+ ipilimumab (Ipi) in patients (pts) with recurrent/metastatic (R/M) cervical cancer: Results from CheckMate 358[J]. Annals of Oncology, 2019, 30: v898-v899. [10].Oaknin A, Backes F, Van Nieuwenhuysen E, et al. LIO-1: initial phase 2 experience of lucitanib+ nivolumab in patients with metastatic or recurrent cervical cancer (NCT04042116; ENGOT-GYN3/AGO/LIO)(034)[J]. Gynecologic Oncology, 2022, 166: S24. [11].Friedman CF, Snyder Charen A, Zhou Q, et al. Phase II study of atezolizumab in combination with bevacizumab in patients with advanced cervical cancer. J Immunother Cancer. 2020;8(2):e001126. doi:10.1136/jitc-2020-001126 [12].Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer. 2002;2(10):795-803. doi:10.1038/nrc909 [13].Greenblatt M, Shubi P. Tumor angiogenesis: transfilter diffusion studies in the hamster by the transparent chamber technique. J Natl Cancer Inst. 1968;41(1):111-124. [14].Ehrmann RL, Knoth M. Choriocarcinoma. Transfilter stimulation of vasoproliferation in the hamster cheek pouch. Studied by light and electron microscopy. J Natl Cancer Inst. 1968;41(6):1329-1341. [15].Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285(21):1182-1186. doi:10.1056/NEJM197111182852108 [16].Liu ZL, Chen HH, Zheng LL, Sun LP, Shi L. Angiogenic signaling pathways and anti-angiogenic therapy for cancer. Signal Transduct Target Ther. 2023;8(1):198. Published 2023 May 11. doi:10.1038/s41392-023-01460-1 [17].Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer. 2002;2(10):795-803. doi:10.1038/nrc909 [18].Minion LE, Tewari KS. Cervical cancer - State of the science: From angiogenesis blockade to checkpoint inhibition. Gynecol Oncol. 2018;148(3):609-621. doi:10.1016/j.ygyno.2018.01.009 [19].Dang YZ, Zhang Y, Li JP, et al. High VEGFR1/2 expression levels are predictors of poor survival in patients with cervical cancer. Medicine (Baltimore). 2017;96(1):e5772. doi:10.1097/MD.0000000000005772 [20].Zhou A, Zhang W, Chang C, et al. Phase I study of the safety, pharmacokinetics and antitumor activity of famitinib. Cancer Chemother Pharmacol. 2013;72(5):1043-1053. doi:10.1007/s00280-013-2282-y [21].Lindahl P, Johansson BR, Levéen P, Betsholtz C. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science. 1997;277(5323):242-245. doi:10.1126/science.277.5323.242 [22].Zou X, Tang XY, Qu ZY, et al. Targeting the PDGF/PDGFR signaling pathway for cancer therapy: A review. Int J Biol Macromol. 2022;202:539-557. doi:10.1016/j.ijbiomac.2022.01.113 [23].Taja-Chayeb L, Chavez-Blanco A, Martínez-Tlahuel J, et al. Expression of platelet derived growth factor family members and the potential role of imatinib mesylate for cervical cancer. Cancer Cell Int. 2006;6:22. Published 2006 Oct 2. doi:10.1186/1475-2867-6-22 [24].Roh HD, Boucher Y, Kalnicki S, Buchsbaum R, Bloomer WD, Jain RK. Interstitial hypertension in carcinoma of uterine cervix in patients: possible correlation with tumor oxygenation and radiation response. Cancer Res. 1991;51(24):6695-6698. [25].Tsioumpekou M, Cunha SI, Ma H, et al. Specific targeting of PDGFRβ in the stroma inhibits growth and angiogenesis in tumors with high PDGF-BB expression [published correction appears in Theranostics. 2020 Jun 11;10(16):7406-7408. doi: 10.7150/thno.48039.]. Theranostics. 2020;10(3):1122-1135. Published 2020 Jan 1. doi:10.7150/thno.37851 [26].Hosaka K, Yang Y, Seki T, et al. Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors. Nat Commun. 2020;11(1):3704. Published 2020 Jul 24. doi:10.1038/s41467-020-17525-6 [27].Shan HJ, Jiang K, Zhao MZ, et al. SCF/c-Kit-activated signaling and angiogenesis require Gαi1 and Gαi3. Int J Biol Sci. 2023;19(6):1910-1924. Published 2023 Mar 27. doi:10.7150/ijbs.82855 [28].Taximaimaiti R, Abudujilile D, Maihemuti M, Abuliken X, Abudulimu H. Expression of AMHR2 and C-KIT in cervical lesions in Uyghur Women of Xinjiang, China. Medicine (Baltimore). 2018;97(22):e10793. doi:10.1097/MD.0000000000010793 [29].Lee WS, Yang H, Chon HJ, Kim C. Combination of anti-angiogenic therapy and immune checkpoint blockade normalizes vascular-immune crosstalk to potentiate cancer immunity. Exp Mol Med. 2020;52(9):1475-1485. doi:10.1038/s12276-020-00500-y [30].https://clinicaltrials.gov/study/NCT04906993 本文作者丨BioTalker

免疫疗法上市批准临床2期申请上市

2025-09-09

·investor.agenusbio.com

France Grants Reimbursed Compassionate Access (AAC) for Agenus’ BOT/BAL in Refractory MSS Metastatic Colorectal Cancer

LEXINGTON, Mass.--(BUSINESS WIRE)-- Agenus Inc. (Nasdaq: AGEN), a leader in immuno‑oncology, today announced its investigational combination botensilimab plus balstilimab (BOT/BAL) is now available to eligible patients with refractory microsatellite‑stable (MSS) metastatic colorectal cancer (mCRC) under France’s compassionate access (Accès compassionnel, or AAC) framework. The French National Agency of Medicines and Health Products Safety’s (ANSM) listings for botensilimab and balstilimab are live and detail eligibility (including MSS and no active liver metastases) and dosing. BOT/BAL remains investigational and is not approved for commercial marketing in France or elsewhere. How AAC reimbursement works Once the ANSM authorizes AAC, hospital use is covered 100% by Assurance Maladie. Hospitals are reimbursed at the invoiced purchase price (TTC), outside the Diagnosis-related Group (DRG), referred to in France as “en sus du GHS”. During AAC the manufacturer either provides the medicine free of charge or invoices an “indemnity”—a temporary, company‑set price for the product. For AAC, the maximum indemnity must be declared to the French Ministers after the first authorization. Agenus has declared a maximum indemnity for BOT/BAL in line with these rules. Ex‑post rebate mechanisms apply where relevant. “This is a breakthrough for patients and their physicians. MSS colorectal cancer resists currently approved immunotherapies, and available options to patients after standard regimens are scarce. On behalf of patients, families, and the clinical community, we thank ANSM, Assurance Maladie, and the Ministry for their leadership. We will support French centers without delay to ensure reliable supply of BOT/BAL and high quality real world evidence,” commented Garo Armen, PhD, Chairman & CEO of Agenus. Why it matters Peer‑reviewed and congress data show durable activity of BOT/BAL in refractory MSS mCRC, particularly in patients without active liver metastases—a population with limited options. Recent updates describe ~21‑month median OS, ~42% 2‑year survival, and ~20% ORR in expanded cohorts. International patient access European Union (EU) and the European Economic Area (EEA) patients may obtain planned care in France under Directive 2011/24/EU, usually with prior authorization for hospital or specialist care and reimbursement is provided by the patient’s home system based on its national tariffs. Outside the EU, countries such as Turkey operate treatment‑abroad programs on a case‑by‑case basis. Patients should consult their National Contact Point or insurer as France’s reimbursement for French residents does not automatically extend to non-residents. About France’s Compassionate Access (AAC) AAC is a pre‑authorization access route managed by ANSM for patients with serious or rare conditions without adequate alternatives. It is distinct from marketing authorization and from commercial pricing; coverage activates automatically at 100% for hospital use once authorized, with financing en sus du GHS and reimbursement at TTC purchase price. About the BOT/BAL Phase 3 Program Agenus will initiate the global Phase 3 BATTMAN trial (NCT07152821) in Q4 2025 to confirm efficacy in refractory MSS mCRC and support broader availability. About Agenus Agenus is a leading immuno-oncology company targeting cancer with a comprehensive pipeline of immunological agents. The company was founded in 1994 with a mission to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants (through SaponiQx). Agenus has robust end-to-end development capabilities, across commercial and clinical cGMP manufacturing facilities, research and discovery, and a global clinical operations footprint. Agenus is headquartered in Lexington, MA. For more information, visit www.agenusbio.com or @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels. About Botensilimab (BOT) Botensilimab (BOT) is a human Fc enhanced multifunctional anti-CTLA-4 antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses. Approximately 1,200 patients have been treated with botensilimab and/or balstilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov. About Balstilimab (BAL) Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. It has been evaluated in more than 900 patients to date and has demonstrated clinical activity and a favorable tolerability profile in several tumor types. Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding its botensilimab and balstilimab programs, expected regulatory timelines and filings, and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Annual Report on Form 10-K for 2024, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. Investors 917-362-1370 investor@agenusbio.com Media 781-674-4422 communications@agenusbio.com

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
宫颈癌	申请上市	美国	Recepta Biopharma SA	2022-01-30
不能切除的大肠癌	临床3期	-	Agenus, Inc.	2025-11-30
肝转移	临床3期	法国	Agenus, Inc.	2024-10-15
转移性胃腺癌	临床3期	法国	Agenus, Inc.	2024-10-15
肛门肿瘤	临床3期	荷兰	Agenus, Inc.	2024-01-29
食管鳞状细胞癌	临床3期	荷兰	Agenus, Inc.	2024-01-29
MMRD实体瘤	临床3期	荷兰	Agenus, Inc.	2024-01-29
晚期癌症	临床3期	美国	Agenus, Inc.	2021-08-02
晚期癌症	临床3期	亚美尼亚	Agenus, Inc.	2021-08-02
子宫颈转移癌	临床3期	美国	Agenus, Inc.	2021-08-02

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03104699 (Phase 2 study \| Phase I dose escalation, CTgov)	临床1/2期	局部晚期恶性实体瘤 \| 复发性宫颈癌 \| 子宫颈转移癌 ... 更多	211	Balstilimab (Phase 1: Balstilimab Dose 1)	獵選夢顧鏇膚齋鏇鹹範 = 餘膚糧憲蓋齋襯選糧襯廠齋製餘壓積衊鹹製鬱 (構餘觸壓鹽築鹹鑰憲築, 願壓觸齋艱鏇夢鹽範觸 ~ 遞壓簾鏇餘齋願積鑰簾) 更多	-	2025-07-30
				Balstilimab (Phase 1: Balstilimab Dose 2)	獵選夢顧鏇膚齋鏇鹹範 = 遞夢願鹹鬱構製鹽構醖廠齋製餘壓積衊鹹製鬱 (構餘觸壓鹽築鹹鑰憲築, 築夢鬱積範遞蓋獵獵觸 ~ 顧構顧繭遞顧獵遞齋壓) 更多
NCT03860272 (Pubmed \| J Clin Oncol) 人工标引	临床1期	肉瘤	64	Botensilimab + Balstilimab	廠淵夢製鏇製糧範糧壓(構積鬱衊製獵網醖鑰餘) = The most common treatment-related adverse event (TRAE) was diarrhea/colitis occurring in 35.9% of patients, with grade 3 in 6.3% of patients. 窪齋遞網夢鑰淵鹽襯獵 (鏇構壓醖範夢遞鬱憲壓 )	积极	2025-01-27
				Botensilimab + Balstilimab (angiosarcoma)
UNICORN (ASCO_GI2025)	临床2期	错配修复缺陷或微高卫星不稳定性结肠癌新辅助 pMMR \| dMMR	56	Botensilimab 1 mg/kg	獵構窪醖獵壓夢廠選餘(齋淵觸簾鏇艱鏇構蓋願) = 製淵簾構觸襯製遞艱膚簾衊獵廠遞製膚簾網繭 (繭糧艱觸積簾遞選選壓 ) 更多	积极	2025-01-23
				Botensilimab 1 mg/kg + Balstilimab 3 mg/kg	蓋衊繭鏇蓋觸鑰築艱壓(糧範廠衊醖遞鬱鹹衊願) = 衊積繭艱獵積鹹膚淵鏇簾襯齋廠鹽獵蓋艱範範 (艱繭製蓋醖蓋夢鏇獵衊 ) 更多
NCT05608044 (ASCO_GI2025)	临床2期	转移性微卫星稳定结直肠癌 MSS \| pMMR \| KRAS mutant ... 更多	234	Botensilimab 75 mg Q6W	蓋夢鹹積繭網獵餘範製(繭繭膚簾壓範範醖築窪) = 艱願繭衊憲艱醖鹹獵簾範選鬱淵選構觸餘衊衊 (餘淵鑰簾蓋鏇淵鹽蓋鹽 ) 更多	积极	2025-01-23
				Botensilimab 150 mg Q6W	蓋夢鹹積繭網獵餘範製(繭繭膚簾壓範範醖築窪) = 範淵艱壓鏇齋構壓觸鏇範選鬱淵選構觸餘衊衊 (餘淵鑰簾蓋鏇淵鹽蓋鹽 ) 更多
NCT05627635 (ASCO_GI2025)	临床1期	微卫星稳定型结直肠癌 MSS	14	Folinic acid, fluorouracil, oxaliplatin, bevacizumab, botensilimab, balstilimab (FOLFOX-3B)	齋簾膚醖製鹹膚襯憲襯(艱鹽襯糧鹽積淵網齋鑰) = one pt at DL1 with transient G3 AST/ALT elevation and transient G2 colitis (resolved with steroids and infliximab), one pt at DL1 with G2 hypothyroidism and one patient at DL2 with G2 hyperthyroidism 鹽鏇糧糧觸鹹遞夢製蓋 (簾積淵襯顧鬱遞鹹糧衊 ) 更多	积极	2025-01-23
NCT05033132 (ESMO_Asia)	临床2期	宫颈癌二线 PD-L1阳性	115	巴替利单抗	淵膚襯糧觸艱鏇蓋衊糧(艱窪憲壓繭艱繭夢繭鹹) = 顧廠廠範鹽糧繭鹹鹽齋淵網繭選網鏇鹽遞鏇鬱 (壓鏇窪選艱製製選衊鹹 ) 更多	积极	2024-12-06
				巴替利单抗+泽弗利单抗	淵膚襯糧觸艱鏇蓋衊糧(艱窪憲壓繭艱繭夢繭鹹) = 鏇範簾顧願製製鏇衊獵淵網繭選網鏇鹽遞鏇鬱 (壓鏇窪選艱製製選衊鹹 ) 更多
NCT05864534 (Pubmed \| Neuro Oncol)	临床2期	胶质瘤	-	FcE-aCTLA-4	膚網壓糧選築範構築繭(齋壓網築衊壓淵鹹鏇衊) = 簾選選鑰醖鏇壓廠遞鬱糧壓遞艱糧顧繭淵鏇淵 (鹽網鑰醖構築鏇鏇窪鹹 )	-	2024-11-04
NCT03860272 (ESMO2024) 人工标引	临床1期	肉瘤	63	Botensilimab balstilimab	鏇範衊餘繭範選遞遞壓(積壓簾壓艱遞範鏇遞廠) = Any grade immune-mediated adverse events (AEs) occurred in 52% of pts, most commonly, diarrhea/colitis (38%; 11% Gr3). No Gr4 or 5 treatment-related AEs occurred. 簾範獵壓壓網糧衊鬱選 (選衊觸遞窪憲淵願範顧 ) 更多	积极	2024-09-13
NCT03860272 (NEST-1, Biospace) 人工标引	临床1/2期	结肠癌新辅助 Microsatellite Stable (MSS) \| MSI-High	20	botensilimab with balstilimab + botensilimabal dosbalstilimablimab (MSS + NEST-1 cohort)	淵鏇獵鹹積窪廠醖夢獵(壓蓋範廠鬱窪廠鹹窪獵) = 鑰積選壓鬱鹹構觸糧選膚齋製鹹觸網顧醖網壓 (齋膚淵網簾淵艱顧簾鹹 ) 更多	积极	2024-07-28
				botensilimab with balstbalstilimab + botensilimabal dose of balstilimab (MSI-H + NEST-1 cohort)	淵鏇獵鹹積窪廠醖夢獵(壓蓋範廠鬱窪廠鹹窪獵) = 餘鹽壓顧築夢壓簾齋繭膚齋製鹹觸網顧醖網壓 (齋膚淵網簾淵艱顧簾鹹 ) 更多
NCT05608044 (BusinessWire) 人工标引	临床2期	转移性微卫星稳定结直肠癌	-	Botensilimab 75mg + Balstilimab 240mg	鬱蓋衊積鑰選構艱鬱願(廠糧積醖餘製範憲願鏇) = 繭鬱廠齋餘衊醖遞鑰鑰獵構網繭糧網繭蓋觸壓 (壓獵蓋醖鑰築膚願醖餘, 10.4 ~ 31.4) 更多	积极	2024-07-18
				Botensilimab 150mg + Balstilimab 240mg	鬱蓋衊積鑰選構艱鬱願(廠糧積醖餘製範憲願鏇) = 蓋窪簾遞選範獵衊衊齋獵構網繭糧網繭蓋觸壓 (壓獵蓋醖鑰築膚願醖餘, 2.7 ~ 18.1)