Paclitaxel Liposomal(Memorial Sloan Kettering Cancer Center)

LEXINGTON, Mass.--(BUSINESS WIRE)-- Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology innovation, today announced data from an investigator-initiated Phase II trial at Memorial Sloan Kettering Cancer Center, investigating botensilimab (BOT) and balstilimab (BAL) in combination with agenT-797, MiNK’s allo-iNKT cell therapy, ramucirumab and paclitaxel in patients with advanced PD-1 refractory gastroesophageal adenocarcinoma. The data are being presented at the American Association for Cancer Research (AACR) Annual Meeting, taking place April 17-22, 2026, in San Diego, CA. This Phase II trial, which is the first to combine BOT and BAL with agenT-797 in patients with gastroesophageal cancer who progressed after frontline therapy, was designed to explore the role of immune priming and treatment sequencing. Patients received induction with agenT-797 (alone or plus BOT/BAL) followed by the full combination regimen, or initiated the combination without induction, with longitudinal biomarker sampling throughout. In this study (n=17), the regimen delivered a 77% DCR with long-term survival beyond 20 months in a subset, and the induction arm showed meaningful gains in PFS (6.9 vs. 3.5 months; HR 0.19; p=0.015) and OS (9.5 vs. 5.2 months), with 43% of induction-treated patients alive at both 12 and 18 months—underscoring that durability and survival may be the most clinically relevant endpoints in this PD-1 refractory population. “These findings illustrate the mechanistic synergy of agenT-797 with botensilimab and balstilimab in this PD-1 refractory setting,” said Dhan Chand, Ph.D., Vice President of Research at Agenus. “The induction approach promoted significant intratumoral infiltration of T cells and dendritic cells, the formation of organized tertiary lymphoid structures in on-treatment biopsy tissue from a patient with durable benefit, and activation of peripheral CD4 and CD8 T-cell populations. These changes are consistent with immune priming and tumor immune reprogramming, providing a biological rationale for the improved progression-free survival observed with the induction strategy.” Efficacy findings from the Phase II (n=17) study included: DCR was observed in 77% of all treated patients, and long-term survival beyond 20 months was seen in a subset Patients who received induction cycle had longer progression-free survival (PFS) than those treated without induction, with median PFS of 6.9 months versus 3.5 months (HR 0.19; p=0.015), supporting the potential importance of immune priming and treatment sequencing. Median overall survival (OS) was 9.5 months in the induction cohort versus 5.2 months without induction, with 43% of induction-treated patients alive at both 12 and 18 months, compared with 20% and 0%, respectively, in the non-induction cohort. The study did not meet its primary endpoint of ORR; however, disease control and longer-term survival observed in a subset of patients support further study of this approach. Correlative analyses showed that treatment with BOT, BAL, and agenT-797 was associated with significant intratumoral T cell and dendritic cell infiltration, the formation of organized tertiary lymphoid structures in on-treatment biopsies from a patient with prolonged benefit, and activation of peripheral CD4 and CD8 T cells. The safety profile was consistent with the component agents. The most common treatment-emergent adverse events among all patients included fatigue, fever, diarrhea, anorexia, nausea and mucositis. Immune-related adverse events included dermatitis, colitis, gastritis, enteritis, hepatitis and hypothyroidism. Additional analysis of the full biospecimen dataset is ongoing and is expected to provide further insight into immune mechanisms, optimal sequencing, and potential biomarkers that could help identify patients most likely to benefit. Presentation Details: Abstract Title: A phase II study of agenT-797, botensilimab (BOT) and balstilimab (BAL) in PD-1 refractory gastroesophageal cancer (GEC) Presenter: Samuel L. Cytryn M.D.; Gastrointestinal Medical Oncologist, Memorial Sloan Kettering Cancer Center Session Name: Phase II and Phase III Clinical Trials Date/Time: April 20, 2026 | 2:00–5:00 PM PT; 5:00-8:00 PM EDT Poster Section: 52 Abstract No.: CT166 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 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 2025, 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

近日，美国宾州艾布拉姆森癌症中心/纪念斯隆-凯特琳癌症中心研究团队合作共同在期刊《Journal for ImmunoTherapy of Cancer》上发表了研究论文，题为“Clinical and translational results from a phase 1 trial of gemcitabine/nab-paclitaxel with nivolumab/ipilimumab or hydroxychloroquine/ipilimumab in untreated metastatic pancreatic adenocarcinoma”，本研究中的A 组和 B 组在转移性胰腺导管腺癌（mPDAC）患者中均显示出令人鼓舞的抗肿瘤活性。在 B 组中，羟氯喹相关的耐受性问题导致了早期停药和药物暴露量减少。这些发现凸显了当前化学免疫疗法的潜力和局限性。尽管这两组都不会扩大规模，但结果进一步证实了化学免疫疗法在 mPDAC 中的持续前景以及优化这些策略的重要性。 胰腺导管腺癌：免疫治疗“遇冷”，耐药机制与生存现状待解 01 胰腺导管腺癌（PDAC）是最致命的恶性肿瘤之一，5 年生存率低于 15%，转移性胰腺导管腺癌（mPDAC）患者的 5 年生存率更是低至约 3%。尽管全身化疗，包括吉西他滨联合白蛋白结合型紫杉醇或 FOLFIRINOX 方案，具有一定的疗效，但其反应通常短暂且伴有显著毒性，这凸显了开发新策略的必要性。与免疫治疗已改变治疗模式的其他实体瘤不同，mPDAC 对免疫检查点抑制（ICI）疗法大多具有耐药性。这种耐药性是由高度免疫抑制的肿瘤微环境（TME）所驱动，其特征为 T 细胞浸润少、肿瘤突变负荷低以及富含抑制性免疫细胞的致密间质屏障。尽管罕见的分子亚型，如微卫星不稳定性高或肿瘤突变负荷高的肿瘤，可能对程序性细胞死亡蛋白 1（PD-1）阻断疗法有反应，但这些病例并不常见。对于大多数患者而言，免疫治疗的反应仍然有限。 B 组：药效学效应 02 流式细胞术显示，在使用吉西他滨/白蛋白结合型紫杉醇和羟氯喹治疗后，循环免疫细胞群发生了动态变化，而在使用伊匹木单抗治疗后，这种变化尤为显著。在第 1 周期第 8 天，记忆和分化状态发生了改变。相反，增殖性 Ki67+ CD4+ FoxP3− 辅助 T 细胞和调节性 T 细胞（Treg）亚群增加，表明早期 T 细胞被激活。在伊匹木单抗给药后，表达 TIGIT 和 CD127 的效应记忆和效应记忆 RA+ CD8+ T 细胞进一步减少，而增殖性 CD8+ Ki67+ 和 PD-1−Ki67+ 细胞群以及 Ki67+ Tregs 仍保持较高水平。值得注意的是，伊匹木单抗治疗后，ICOS+ 和 CD38+ CD4+ 亚群增加。这些发现表明，在 B 组中，特别是 CTLA-4 阻断后，治疗促进了 T 细胞的激活和增殖，同时重塑了抑制性和分化相关标志物。 研究人员通过透射电子显微镜对自噬体（AV）进行定量，评估了羟氯喹对外周血单个核细胞（PBMCs）自噬抑制作用。正如预期的那样，在未接受羟氯喹治疗的 A 组中，各时间点的 AV 积累量无显著变化。在 B 组中，C1D22 时的 AV 水平与基线水平相当，但在 C2D22 时观察到 AV 积累量有增加的趋势。B 组中有一名患者（2B）未按医嘱服用羟氯喹（仅服用了预期剂量的约 20%），其 AV 积累量呈下降趋势。排除该患者后，C2D22 时 AV 积累量的增加具有统计学意义。未观察到 AV 积累量与临床反应之间的关联。这些发现证实了羟氯喹在 C2D22 时增加了 PBMCs 中的 AV 积累，这与其药效学作用相符，但表明可能需要持续的药物暴露或更有效、更特异的自噬抑制才能产生可测量的影响。 化疗、羟氯喹和伊匹木单抗的药效学效应 结论 03 总之，本研究结果突显了化学免疫疗法联合用药在转移性胰腺导管腺癌（mPDAC）中的潜力，这种疾病一直以来都以预后不良和治疗进展有限而著称。尽管由于临床信号之外的因素，目前这两种治疗方案都不会以现有的形式推进，但观察到的不同药效学效应为未来试验的设计、联合治疗策略以及治疗顺序提供了宝贵的见解。 参考资料： https://jitc.bmj.com/content/14/1/e012864-1 【关于投稿】 转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！ 转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。 责任声明：本稿件如有错误之处，敬请联系转化医学网客服进行修改事宜！ 微信号：zhuanhuayixue