Durvalumab

点击蓝字 关注我们 本 期 看 点 2025年欧洲肿瘤内科学会（ESMO 2025）将于10月17-21日在德国柏林举行。作为全球肿瘤学领域的顶尖盛会，多项即将改变临床实践的重磅研究将在本届大会发布。目前，大会“突破性摘要”（LBA）的标题已经公布。 四项“重磅 LBA”格外值得关注：NorthStar（EGFR）、SKYSCRAPER-03（III 期不可切除）、MDT-BRIDGE（围手术期）与 Beamion LUNG 1（HER2）。 无论是针对 EGFR 突变、HER2 突变，还是局部晚期 III 期不可切除的 NSCLC，几项关键临床试验的结果有望对未来标准治疗产生深远影响。 本期内容 01 四大重磅研究全景速览 02 宗艾替尼（Zongertinib）丨Her2 TKI 03 TIGIT作用机制及研发前景 04 总结与展望 【01 四大重磅研究全景速览】 LBA72: NorthStar 试验 标题： NorthStar: A Phase II Randomized Study of Osimertinib (OSI) With or Without Local Consolidative Therapy (LCT) for Metastatic EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) NorthStar：奥希替尼（OSI）联合或不联合局部巩固治疗（LCT）用于转移性 EGFR 突变型非小细胞肺癌（NSCLC）的 Ⅱ 期随机研究 汇报人：Yasir Y. Elamin 研究设计： II 期随机研究，比较奥希替尼（Tagrisso）单用 vs 奥希替尼 + 局部巩固治疗（手术/放疗） 入组人群：EGFR 突变、IIIB–IV 期 NSCLC 主要终点：无进展生存期（PFS） 次要终点：总生存期（OS） 研究亮点：该研究直击一个核心问题—在靶向治疗时代，局部治疗是否还能进一步延长 EGFR 突变患者的生存？ LBA69: SKYSCRAPER-03 试验 标题： SKYSCRAPER-03: Phase 3, open-label, randomised study of atezolizumab (atezo) + tiragolumab (tira) vs durvalumab (durva) in locally advanced, unresectable, stage Ⅲ non-small cell lung cancer (NSCLC) after platinum-based concurrent chemoradiation (cCRT) SKYSCRAPER-03：Ⅲ期、开放标签、随机研究：阿替利珠单抗（atezo）+tiragolumab（TIGIT单抗）对比度伐利尤单抗（durva）治疗铂类同步放化疗（cCRT）后局部晚期、不可切除的 Ⅲ 期非小细胞肺癌（NSCLC） 汇报人：Rafal Dziadziuszko Pivotal trials of tiragolumab 研究设计： III 期、开放标签、随机研究 比较方案：阿替利珠单抗（Atezo）+ tiragolumab vs 度伐利尤单抗（Durva） 入组人群：局部晚期、不可切除 III 期 NSCLC，且在至少 2 个周期同步放化疗后未进展 主要终点：PFS 次要终点：OS 背景提醒：前期 SKYSCRAPER-01 研究 并未在一线治疗中证明 tiragolumab + 阿替利珠单抗的显著获益，此次结果能否逆袭，备受期待。 LBA65: MDT-BRIDGE 试验 标题： Neoadjuvant durvalumab (D) + chemotherapy (CT) followed by either surgery (Sx) and adjuvant D or CRT and consolidation D in patients (pts) with resectable or borderline resectable stage IIB–IIIB NSCLC: interim analysis (IA) of the phase 2 MDT-BRIDGE study 新辅助度伐利尤单抗（D）+ 化疗（CT），随后行手术（Sx）+ 辅助度伐利尤单抗，或放化疗（CRT）+ 巩固度伐利尤单抗，用于可切除或边界可切除 IIB–IIIB 期非小细胞肺癌（NSCLC）患者：II 期 MDT-BRIDGE 研究的期中分析（IA） 汇报人：Yasir Y. Elamin 研究设计： II 期单臂研究，探索度伐利尤单抗（D）+ 化疗的新辅助治疗模式 主要终点：切除率 次要终点：pCR 率、OS、EFS、PFS、ctDNA 清除率等 意义：探索如何通过“免疫 + 化疗”新辅助策略，扩大可切除窗口，并在围手术期延长获益。 LBA74: Beamion LUNG 1 试验 标题： Zongertinib as first-line treatment in patients with advanced HER2-mutant NSCLC: Beamion LUNG 1 Zongertinib作为晚期HER2突变型非小细胞肺癌（NSCLC）患者的一线治疗：Beamion LUNG 1研究 汇报人：Sanjay Popat 研究设计：开放标签、剂量递增 + 扩展研究 药物：zongertinib（Hernexeos，原 BI 1810631），HER2 突变靶向药 研究进展： Part 1：确定最大耐受剂量（既治患者，HER2 改变实体瘤） Part 2：入组 NSCLC，HER2 突变，既治与初治人群，评估肿瘤缩小率与缓解持续时间 里程碑：基于 Beamion LUNG 1 数据，FDA 已于 2025 年 8 月加速批准 zongertinib，用于不可切除或转移性非鳞 NSCLC，HER2 激酶结构域激活突变。 【02 宗艾替尼（Zongertinib）丨Her2 TKI】 2025年8 月 29 日，中国 NMPA 批准勃林格殷格翰的宗艾替尼（Zongertinib，BI 1810631）片上市，单药用于治疗存在 HER2（ERBB2）激活突变且既往接受过至少一种系统治疗的不可切除局晚期或转移性 NSCLC 成人患者。 来源：NMPA 官网 宗艾替尼为选择性 HER2 抑制剂，可共价结合 HER2 外显子 20 突变的激酶结构域，对主要 HER2 突变（含 YVMA 插入）均具强抑制活性，且不抑制 EGFR 野生型，有望降低泛-HER TKI 常见的野生型 EGFR 相关毒性。2024 年 4 月，宗艾替尼被纳入勃林格殷格翰 × 中国生物制药在中国大陆的战略合作。 核心证据（BEAMION LUNG-1 试验，Ib 期）该开放性 Ia/Ib 剂量递增与扩展研究在 HER2 异常的晚期/转移性实体瘤人群开展，主要终点为 BICR 与研究者评估的 ORR。Ib 期设置多队列：队列1（经治 HER2-TKD 突变 NSCLC，QD 120mg 或 240mg；期中确定120mg为后续剂量）、队列3（经治 HER2 突变 NSCLC，含 TKD 与非 TKD）、队列5（经治 HER2-TKD，且既往含铂 + HER2-ADC）。 关键疗效截至 2024-11-29：队列1（n=75，120mg） BICR-ORR 71%、DCR 96%，中位 DoR 14.1 个月、中位 PFS 12.4 个月；合并脑转移的可评价患者（n=27）颅内 ORR 41%、DCR 81%。队列3（非 TKD，n=20） ORR 30%、DCR 65%（DoR/PFS 未成熟）。队列5（ADC 后，n=31） ORR 48%、DCR 97%，中位 DoR 5.3 个月、中位 PFS 6.8 个月。此前 ESMO Asia 与 AACR 公布的数据与 NEJM 同步发表，显示疗效持久且具临床意义。 安全性概览不良事件以腹泻最常见；药物相关 AE（全部/≥3 级）发生率：队列1 97%/17%、队列3 80%/25%、队列5 77%/3%；未见药物相关 ILD 或心脏毒性。总体安全谱可管理，支持进一步在一线联合/序贯及特殊亚组（如脑转移）中的探索。 03 TIGIT作用机制及研发前景 TIGIT 靶点与机制 TIGIT与其同源配体PVR的结合直接抑制淋巴细胞激活。TIGIT和PVR广泛表达在不同类型的实体瘤中，说明TIGIT-PVR信号通路可能是一种主要的肿瘤免疫逃逸机制，是继PD-1/PD-L1之后的新型免疫检查点。但曾被寄予厚望的TIGIT靶点。但TIGIT单抗接连失利 ，为该赛道的研发蒙上阴影。 阻断 TIGIT 通路，理论上可增强 PD-(L)1 抑制剂的疗效，因此成为免疫联合的重要新方向。 临床探索：阿替利珠单抗 + TIGIT 抗体（tiragolumab） SKYSCRAPER-01（III 期，一线转移性 NSCLC）比较 tiragolumab + 阿替利珠单抗 vs 阿替利珠单抗单药。 结果：未显著改善 PFS 或 OS，让业界对 TIGIT 路线的信心受挫。 SKYSCRAPER-03（III 期，局部晚期不可切除 NSCLC） 人群：完成至少 2 周期同步放化疗未进展的 III 期患者。 设计：阿替利珠单抗 + tiragolumab vs 度伐利尤单抗。 主要终点为 PFS。 意义：尝试在 cCRT 后巩固治疗 场景对抗 “度伐利尤单抗独霸”的格局。 市场与临床高度关注结果能否“翻盘”，决定 TIGIT 路线未来走向。 TIGIT 在肺癌的现状与前景 挫折与希望并存：SKYSCRAPER-01 的失败让 TIGIT 通路的普适性受到质疑，但在免疫微环境不同的场景（如 III 期 cCRT 后），仍可能展现独特价值。 生物标志物需求：未来或需结合 PD-L1、TMB、免疫谱，精细筛选最可能受益的亚群。 开发趋势：目前多家药企（罗氏、百济神州等）都在积极推进 TIGIT 抗体单药或联合方案，焦点逐渐转向耐药后的二次机会和围手术期探索。 04 总结与展望 2025 年 ESMO 大会前夕，肺癌领域的四项重磅研究（NorthStar、SKYSCRAPER-03、MDT-BRIDGE、Beamion LUNG 1）共同勾勒出未来治疗格局的新图景。靶点突变（EGFR、HER2）仍是驱动治疗升级的核心，免疫联合在局部晚期与围手术期的探索持续深入，而 ctDNA、pCR 等新型终点也逐渐走向舞台中央。 短期来看，这些研究将直接影响临床指南的更新，推动“系统+局部”的综合管理、“新辅助+巩固”的一体化路径，以及 HER2 靶点从 ADC 向小分子+ADC 双轮驱动的演进。长期来看，真正的挑战在于：如何通过精准分层，将合适的患者匹配到最有价值的方案，并在多种策略之间找到最佳时机与组合。 可以预见，随着这些试验结果的揭晓，肺癌治疗将进入一个更加多维度、个体化的新阶段。对于临床医生，这是决策复杂度提升的开始；而对药企与研发者而言，则是重塑赛道格局的窗口期。 ★

PARIS and CAMBRIDGE, Mass., Sept. 30, 2025 (GLOBE NEWSWIRE) -- NANOBIOTIX (Euronext: NANO - NASDAQ: NBTX - the “Company”), a late-clinical stage biotechnology company pioneering nanotherapeutic approaches to expand treatment possibilities for patients with cancer and other major diseases, provided an update on operational progress and announced its half year financial results for the six-month period ended June 30, 2025. Operational Highlights of the 2025 Half Year Period and To Date Expanding clinical development program evaluating the potential broad applicability of JNJ-1900 (NBTXR3) continues to build significant momentum: First patient dosed in the CONVERGE study, a Johnson & Johnson (“J&J”)-sponsored randomized Phase 2 study evaluating JNJ-1900 (NBTXR3) for patients with Stage 3 unresectable non-small cell lung cancer receiving standard of care chemoradiation followed by consolidation durvalumab First data announced from the completed dose escalation part of a Phase 1 study evaluating JNJ-1900 (NBTXR3) as a 2L+ therapy for patients with locally advanced NSCLC, sponsored by the University of Texas MD Anderson Cancer Center Announced full data from the completed MD Anderson Phase 1 study evaluating JNJ-1900 (NBTXR3) in pancreatic cancer along with the launch of a new cohort and expansion of the trial Achieved regulatory harmonization of JNJ-1900 (NBTXR3) after agreement with health authorities in major European countries to reclassify JNJ-1900 (NBTXR3) from a medical device to a drug Filed a new composition of matter patent for JNJ-1900 (NBTXR3) that aims to reinforce the intellectual property foundation supporting the product candidate First data announced from a Nanobiotix-sponsored Phase 1 study evaluating JNJ-1900 (NBTXR3) in combination with immune checkpoint inhibitors for patients with primary cutaneous melanoma resistant to anti-PD-1 Updated data announced from a Nanobiotix-sponsored Phase 1 study continuing to support JNJ-1900 (NBTXR3) plus anti-PD-1 as a potential new 1L or 2L+ option in anti-PD-1 naïve or resistant R/M-HNSCC Further execution of disciplined financial plan to reinforce pathway to long-term, self-sustained growth: Strengthened financial position through amendment of the JNJ-1900 (NBTXR3) global licensing agreement extending cash visibility to mid-2026 In active discussions regarding non-dilutive financing, intended to meaningfully extend its cash runway beyond mid-2026. Half Year 2025 Financial Results Revenue and Other Income: Revenue and other income have increased for the six months ended June 30, 2025, up to €26.6 million, compared to €9.3 million for the same period in 2024. Further to J&J amendment letter signed in March 2025 reducing the Company’s funding obligation on the future NANORAY-312 study costs, a positive non-cash revenue impact amounting to €21.2m was recorded in accordance with IFRS15 revenue recognition accounting principles application, offsetting the negative non-cash revenue impact recognized in 2024 results following the transfer of NANORAY-312 study sponsorship to J&J signed at the end of 2024. In addition, revenue towards J&J also included €3.4m of clinical product sales to J&J and R&D tax credit income of 1.7 million. Research and Development (“R&D”) Expenses: R&D expenses consist primarily of preclinical, clinical and manufacturing expenses including employee-related payroll expenses related to the development of JNJ-1900 (NBTXR3). These expenses for the six months ending June 30 2025, were €14.5 million compared to €22.0 million for the same period in 2024. This favorable R&D cost decrease was primarily driven by lower clinical development activities in NANORAY-312 study further to the transfer of sponsorship to J&J which has assumed nearly all remaining study expanses, less a small portion of costs that remain covered by the Company. Selling, General and Administrative (“SG&A”) Expenses: SG&A expenses consist primarily of administrative employee-related payroll expenses, legal and other professional fees, patent filing and maintenance fees, and insurance. Total SG&A expenses for the six months ending June 30, 2025, were €11.3 million, which is quite stable compared to €10.8 million for the same period in 2024. This slight unfavorable variance is mainly due to a phasing issue of social contributions expenses. Net loss: Net loss attributable to common shareholders for the six months ending June 30, 2025, was €5.4 million, or a €0.11 basic loss per share. This compares to a net loss attributable to common shareholders of €21.9 million, or €0.46 basic loss per share, for the same period in 2024. Cash and Cash Equivalents: Cash and cash equivalents as of June 30, 2025, were €28.8 million, compared to €49.7 million as of December 31, 2024. Financial Guidance: Based on the current operating plan and financial projections, the Company anticipates that the cash and cash equivalents of €28.8 million as of June 30, 2025, will fund its operations into mid-2026, similar to its prior guidance. Going Concern: In March 2025, the Company and J&J executed an amendment to the License Agreement. The amendment provides that J&J will assume nearly all remaining costs for the ongoing pivotal Phase 3 trial through completion, less a small portion of costs that will remain covered by the Company, allowing the Company to extend its cash runway and to reduce its operating cash outflows post this amendment, including the period beyond mid-2026. With the available €28.8 million of cash and cash equivalents as of June 30, 2025 and based on its current operating plan, the Company anticipates that its existing cash and cash equivalents will be insufficient to fund its operations over the next twelve months following the issuance of interim condensed consolidated financial statements. These events and conditions indicate that a material uncertainty exists that may cast significant doubt on the Company’s ability to continue as a going concern and, therefore, the Company may be unable to realize its assets and discharge its liabilities in the normal course of business. However, as the Company is in active discussions regarding non-dilutive financing intended to meaningfully extend its cash runway beyond the 12 months, the executive board determined it is appropriate to prepare the interim condensed consolidated financial statements as of and for the six-month period ended June 30, 2025, on a going concern basis, assuming the Company will continue to operate for the foreseeable future and to address its liquidity challenges by pursuing activities to generate additional cash inflows and by closely managing its operating expenditures, based on assumptions described in the half-year 2025 financial report. Availability of the Half Year 2025 Financial Reports The 2025 half-year financial report has been filed with the French financial market authority (Autorité des marchés financiers). It is available to the public on the Company’s website, www.nanobiotix.com. About NANOBIOTIX Nanobiotix is a late-stage clinical biotechnology company pioneering disruptive, physics-based therapeutic approaches to revolutionize treatment outcomes for millions of patients; supported by people committed to making a difference for humanity. The Company’s philosophy is rooted in the concept of pushing past the boundaries of what is known to expand possibilities for human life. Incorporated in 2003, Nanobiotix is headquartered in Paris, France and is listed on Euronext Paris since 2012 and on the Nasdaq Global Select Market in New York City since December 2020. The Company has subsidiaries in Cambridge, Massachusetts (United States) amongst other locations. Nanobiotix is the owner of more than 25 patent families associated with three (3) nanotechnology platforms with applications in 1) oncology; 2) bioavailability and biodistribution; and 3) disorders of the central nervous system. For more information about Nanobiotix, visit us at www.nanobiotix.com or follow us on LinkedIn and Twitter. DisclaimerThis press release contains “forward-looking” statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the use of proceed therefrom, and the period of time through which the Company’s anticipates its financial resources will be adequate to support operations. Words such as “expects”, “intends”, “can”, “could”, “may”, “might”, “plan”, “potential”, “should” and “will” or the negative of these and similar expressions are intended to identify forward-looking statements. These forward-looking statements which are based on the Company’ management’s current expectations and assumptions and on information currently available to management. These forward-looking statements involve known and unknown risks, uncertainties and other factors that could cause actual results to differ materially from those implied by the forward-looking statements, including risks related to Nanobiotix’s business and financial performance, which include the risk that assumptions underlying the Company’s cash runway projections are not realized. Further information on the risk factors that may affect company business and financial performance is included in Nanobiotix’s Annual Report on Form 20-F filed with the SEC on April 2, 2025 under “Item 3.D. Risk Factors”, in Nanobiotix’s 2024 universal registration document filed with the AMF on April 2, 2025 under “chapter 1.5 Risk Factors”, and subsequent filings Nanobiotix makes with the SEC and AMF from time to time, including the Half-Year Report at June 30, 2025 which are available on the SEC’s website at www.sec.gov and on the AMF's website at www.amf.org, The forward-looking statements included in this press release speak only as of the date of this press release, and except as required by law, Nanobiotix assumes no obligation to update these forward-looking statements publicly. Contacts Attachment 2025-09-30 -- NBTX -- 1H25 Financial Results -- FINAL