Cetuximab

Treatment remained well-tolerated with consistent injection feasibility in 103 heavily pre-treated patients with R/M-HNSCC naïve or resistant to anti-PD-1 63% (26/41) disease control rate (“DCR”) and 37% (15/41) objective response rate (“ORR”) in evaluable anti-PD-1 naïve patients per RECIST 1.1 74% (37/50) DCR and 32% (16/50) ORR in evaluable anti-PD-1 resistant patients per RECIST 1.1 15.5 months median Overall Survival (“mOS”) in evaluable anti-PD-1 naïve patients 11.4 months mOS in evaluable anti-PD-1 resistant patients Investigators concluded that these promising results warrant further exploration in randomized controlled trials Data presented as a “Top-rated Abstract in Head and Neck Cancer” at the 2025 Annual Meeting of the American Society for Radiation Oncology (ASTRO) on September 29th PARIS and CAMBRIDGE, Mass., Sept. 29, 2025 (GLOBE NEWSWIRE) -- NANOBIOTIX (Euronext: NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-stage clinical biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer and other major diseases, today announced updated data from cohorts 1 and 2 of Study 1100, a multicenter Phase 1 dose escalation and expansion trial evaluating JNJ-1900 (NBTXR3) activated by radiation therapy (“RT”) followed by anti-PD-1 immune checkpoint inhibitors (pembrolizumab or nivolumab; “ICIs”) in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (“R/M-HNSCC”) that is naïve (cohort 1) or resistant (cohort 2) to prior anti-PD-1 therapy. Study results were presented as a “Top-rated Abstract in Head and Neck Cancer” by Study 1100 Coordinating Investigator Colette Shen, MD, PhD, Assistant Professor of Radiation Oncology, University of North Carolina Lineberger Comprehensive Cancer Center, at the 2025 Annual Meeting of the American Society of Radiation Oncology (ASTRO). ABSTRACT #245: PHASE 1 DOSE ESCALATION/DOSE EXPANSION TRIAL OF NBTXR3/SBRT IN COMBINATION WITH NIVOLUMAB OR PEMBROLIZUMAB FOR TREATMENT OF ANTI-PD-1 NAÏVE OR RESISTANT PATIENTS WITH RECURRENT/METASTATIC HEAD AND NECK SQUAMOUS CELL CARCINOMAColette Shen1, Ammar Sukari2, William A. Stokes3, George Yang4, Nabil F. Saba3, Jared Weiss1, Jessica Frakes4, Jimmy Caudell4, Paul Chang5, Septimiu Murgu5, Michele Lohr6, Jason Chan7, Kedar Kirtane4, David Rolando8, Omar I. Vivar8, Zhen Gooi5, Aditya Juloori5, Trevor Hackman1, Ari Rosenberg51University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA; 2Karmanos Cancer Institute, Detroit, MI, USA; 3Emory Winship Cancer Institute, Atlanta, Georgia, USA; 4Moffitt Cancer Center, Tampa, Florida, USA; 5The University of Chicago, Chicago, Illinois, USA; 6Sanford Cancer Center, Sioux Falls, South Dakota, USA; 7UCSF, San Francisco, CA, USA; 8Nanobiotix, SA, Paris, France The efficacy of ICI monotherapy remains limited in R/M-HNSCC, with objective response rates between approximately 13% and 18%, and median Overall Survival (“mOS”) between approximately 8 months and 12 months. As approximately 66% of patients with R/M-HNSCC experience disease recurrence locally or loco-regionally, addition of RT to the treatment regimen is often recommended to improve local control and as a potential option for stimulating immune responses. However, to date, the addition of RT has not significantly improved ICI efficacy in R/M-HNSCC. As such, patients with R/M-HNSCC have an unmet need for novel treatment strategies that can improve local tumor control and potentiate systemic immune response. Safety and Feasibility JNJ-1900 (NBTXR3) activated by RT followed by anti-PD-1 was consistently well-tolerated and remained feasible in this heavily pre-treated patient population (n=103): Injection remained consistently feasible at the recommended Phase 2 dose (33% GTV) Favorable safety profile including no additional toxicities in lesions that were injected after re-irradiation 27 patients experienced treatment-emergent adverse events (TEAEs) of any grade (1, 2, or 3+) related to JNJ-1900 (NBTXR3) and 32 patients experienced TEAEs of any grade related to the injection procedure Of these patients, 5 experienced grade 3+ TEAEs related to JNJ-1900 (NBTXR3) and 4 experienced grade 3+ TEAEs related to the injection procedure In total, 71 patients experienced TEAEs of any grade related to the overall therapeutic regimen Patients were deemed non-evaluable for efficacy (n=12) if more than one RT session was missed and/or a post-treatment tumor response assessment was unavailable Of these patients, 5 experienced grade 3+ TEAEs related to JNJ-1900 (NBTXR3) and 4 experienced grade 3+ TEAEs related to the injection procedure Signals of Efficacy Potential enhancement of local responses: Evaluable Anti-PD-1 Naïve Patients (n=41) Injected-lesion Disease Control Rate (“DCR”): 95% (39/41) Injected-lesion Overall Response Rate (“ORR”): 66% (27/41) Local Progression-free Survival (“LPFS”): 34.4 months [95% CI: 12.8; Not Reached] Evaluable Anti-PD-1 Resistant Patients (n=50) Injected-lesion DCR: 94% (47/50) Injected-lesion ORR: 50% (25/50) LPFS: 7.3 months [95% CI: 5.7; Not Reached] Injected-lesion Disease Control Rate (“DCR”): 95% (39/41) Injected-lesion Overall Response Rate (“ORR”): 66% (27/41) Local Progression-free Survival (“LPFS”): 34.4 months [95% CI: 12.8; Not Reached] Injected-lesion DCR: 94% (47/50) Injected-lesion ORR: 50% (25/50) LPFS: 7.3 months [95% CI: 5.7; Not Reached] Systemic responses beyond potential enhanced local control: Evaluable Anti-PD-1 Naïve Patients DCR per RECIST 1.1: 63% (26/41) ORR per RECIST 1.1: 37% (15/41) Evaluable Anti-PD-1 Resistant Patients DCR per RECIST 1.1: 74% (37/50) ORR per RECIST 1.1: 32% (16/50) DCR per RECIST 1.1: 63% (26/41) ORR per RECIST 1.1: 37% (15/41) DCR per RECIST 1.1: 74% (37/50) ORR per RECIST 1.1: 32% (16/50) Early signals of Overall Survival that is expected to mature with additional follow up: Evaluable Anti-PD-1 Naïve Patients Median Overall Survival: 15.5 months [95% CI: 11.0; Not Reached] Evaluable Anti-PD-1 Resistant Patients Median Overall Survival: 11.4 months [95% CI: 7.8; 16.7] Median Overall Survival: 15.5 months [95% CI: 11.0; Not Reached] Median Overall Survival: 11.4 months [95% CI: 7.8; 16.7] Notably, survival data in anti-PD-1 resistant patients suggests JNJ-1900 (NBTXR3) activated by RT followed by anti-PD-1 may overcome prior resistance to immune checkpoint inhibitors. Overall, these results show strong local control, with an aggregate DCR of 95% (86/91) in JNJ-1900 (NBTXR3)-injected lesions in evaluable patients, representing a critical potential outcome for patients with R/M-HNSCC. Moreover, the results suggest that the antitumoral activity of JNJ-1900 (NBTXR3) activated by RT may occur beyond the injected lesion. Investigators concluded that these promising results warrant further exploration in randomized controlled trials. “Through the evaluation of JNJ-1900 (NBTXR3) cohorts 1 and 2 of Study 1100, we are ensuring that we prioritize the clinical development of innovation that acts both locally and systemically to address the unmet needs of patients with R/M-HNSCC,” said Study 1100 Coordinating Investigator Colette Shen, MD, PhD. “Our findings from Study 1100 have consistently supported a well-tolerated safety profile with early efficacy signals, and I look forward to further investigation of JNJ-1900 (NBTXR3) as a potentially new and complementary therapeutic option for patients." About JNJ-1900 (NBTXR3) JNJ-1900 (NBTXR3) is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. Its proof-of-concept was achieved in soft tissue sarcomas through a successful randomized Phase 2/3 study in 2018. The product candidate’s mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that JNJ-1900 (NBTXR3) could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors. Radiotherapy-activated JNJ-1900 (NBTXR3) is being evaluated across multiple solid tumor indications as a single agent or combination therapy. The program is led by NANORAY-312—a global, randomized Phase 3 study in locally advanced head and neck squamous cell cancers. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of JNJ-1900 (NBTXR3) activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy—the same population being evaluated in the Phase 3 study. Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3, Nanobiotix has engaged in a collaboration strategy to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several Phase 1 and Phase 2 studies evaluating JNJ-1900 (NBTXR3) across tumor types and therapeutic combinations. In 2023, Nanobiotix announced a license agreement for the global co-development and commercialization of JNJ-1900 (NBTXR3) with Johnson & Johnson. 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 umbrella patents 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 Disclaimer This 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 02, 2025 under “Item 3.D. Risk Factors”, in Nanobiotix’s 2024 universal registration document filed with the AMF on April 02, 2025,, and subsequent filings Nanobiotix makes with the SEC from time to time which are available on the SEC’s website at www.sec.gov. 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 2025-09-29 -- NBTX -- Updated Ph1 Results for NBTXR3 -- FINAL

编者按：结直肠癌是全球最常见的恶性肿瘤之一，其发病率和死亡率居高不下。近年来，该领域治疗手段不断进步，患者的选择日益丰富，疾病治疗状况得到了极大改善。但当前临床仍面临诸多挑战。令人期待的是，目前全球有数百项结直肠癌新药研发管线处于临床研究阶段，为结直肠癌患者带来新的希望。作为医药创新的赋能者，药明康德长期以来通过独特的CRDMO模式，持续助力全球合作伙伴加速包括结直肠癌在内的各类癌症创新药物研发，推动更多突破性疗法早日落地，为战胜结直肠癌贡献力量。 结直肠癌是全球范围内严重威胁人类健康的主要恶性肿瘤之一。根据CA：A Cancer Journal for Clinicians发布的2022年全球癌症统计报告，结直肠癌的发病率位居全球癌症谱第三位，其死亡率位列癌症相关死亡原因第二位。更值得警惕的是，近年来结直肠癌发病呈现显著的“年轻化”趋势——50岁以下患者占比持续攀升，成为公共卫生领域的重要挑战之一。 目前，结直肠癌领域已建立起多手段协同的综合治疗体系。除手术和传统放化疗之外，近年来靶向治疗和免疫治疗等领域取得的突破，为携带特定分子标志物的患者带来了更长的生存获益，也推动结直肠癌治疗逐步进入“精准化”时代。 尽管治疗手段日益丰富，结直肠癌的整体预后仍不理想，尤其是转移性结直肠癌，其治疗形势依然严峻，5年生存率在15%以下。更严峻的是，对于经手术、放化疗、靶向及免疫等多线方案治疗后仍出现疾病进展的“难治性”结直肠癌患者，其后续生存期往往进一步缩短。这类患者的未竟医疗需求尤为迫切。 为响应这一需求，全球目前针对结直肠癌的临床在研管线项目有数百个，覆盖各类创新靶点和创新分子类型。长期以来，药明康德始终支持包括结直肠癌在内的各类癌症创新疗法的研发，依托“一体化、端到端”的CRDMO模式，助力合作伙伴将科学突破高效转化为创新药物。在全球监管机构批准的数十款结直肠癌治疗药物中，就有多款得到了药明康德的支持。 图片来源：123RF 2025年以来，结直肠癌新药研发领域迎来多项新进展。 小分子靶向疗法迎来多项突破 1月，安进（Amgen）开发的KRAS G12C抑制剂Lumakras（sotorasib）联合EGFR抑制剂Vectibix（panitumumab）获美国FDA批准，用于治疗携带KRAS G12C突变且既往接受过特定化疗的转移性结直肠癌（mCRC）患者。这一联合方案的上市，为此类患者提供了新的治疗选择。 5月，辉瑞（Pfizer）公布了其BRAF V600E抑制剂Braftovi（恩考芬尼，encorafenib）联合西妥昔单抗与化疗方案mFOLFOX6的3期临床数据。结果显示，该联合方案较现有标准治疗可将BRAF V600E突变mCRC患者的死亡风险降低51%。随后在7月，中国国家药品监督管理局（NMPA）批准恩考芬尼联合西妥昔单抗用于既往接受过系统治疗的BRAF V600E突变mCRC患者。 8月，Cardiff Oncology公布其PLK1抑制剂onvansertib联合标准治疗（SOC）一线治疗RAS突变mCRC的2期临床数据。结果显示，30mg剂量组的客观缓解率（ORR）达到49%，显著高于对照组的30%；同时，该联合方案还显著改善了患者的早期无进展生存期（PFS），且整体耐受性良好。PLK1是Polo样激酶家族成员之一，在多种实体瘤和血液癌症中高度表达，且被认为是维持细胞正常分裂的基石之一。研究显示，RAS的激活会引发PLK1的激活，导致细胞分裂和肿瘤增殖，因此，通过抑制PLK1的活性，onvansertib有望抑制肿瘤生长。 同月，Larkspur Biosciences首次公开其口服小分子降解剂LRK-4189的分子结构。该药物通过靶向脂质激酶PIP4K2C，在结直肠癌临床前模型中表现出显著的抗肿瘤活性，无论单药或联合化疗均有效。目前，LRK-4189的新药临床试验申请（IND）所需的前期研究已完成，预计将在2025年第四季度启动1期临床试验。PIP4K2C已被证实与结直肠癌等多种肿瘤的不良预后密切相关，肿瘤细胞通过利用PIP4K2C提升生存能力，避免免疫监视并耐受压力。 免疫治疗持续拓宽患者人群 在结直肠癌患者中，微卫星高度不稳定（MSI-H）与错配修复缺陷（dMMR）是两类常见的遗传异常。这类变异会影响细胞内的DNA修复机制，导致肿瘤细胞突变积累和肿瘤突变负荷增高，从而增强免疫原性。因此，MSI-H/dMMR型肿瘤通常对免疫治疗更为敏感。 2025年以来，免疫治疗在结直肠癌领域的应用持续拓展，从传统的MSI-H/dMMR优势亚型，逐步延伸至微卫星稳定（MSS）及耐药等更难治的患者群体。 在非MSI-H型mCRC方面，Exelix公司于6月公布了其多靶点酪氨酸激酶抑制剂zanzalintinib联合PD-L1抑制剂Tecentriq（阿替利珠单抗，atezolizumab）用于经治非MSI-H型mCRC的3期研究数据。结果显示，该联合疗法显著延长了患者的总生存期，为此类mCRC患者提供了后线治疗的潜在策略。 对于MSI-H/dMMR型mCRC患者，免疫检查点抑制剂的组合方案展现出显著疗效。2月，百时美施贵宝（Bristol Myers Squibb）公布了PD-1抑制剂Opdivo（纳武利尤单抗，nivolumab）联合CTLA-4抑制剂Yervoy（伊匹木单抗，ipilimumab）治疗MSI-H/dMMR型mCRC的3期长期随访数据。结果显示，在所有治疗线中，该联合方案较Opdivo单药可降低38%的疾病进展或死亡风险。基于该结果，美国FDA于4月正式批准其用于不可切除或转移性MSI-H/dMMR结直肠癌的一线治疗。 针对耐药患者的创新疗法也取得进展。Marengo Therapeutics在4月公布了其T细胞激活剂invikafusp alfa的1/2期临床试验更新结果：该药物在肿瘤突变负荷高（TMB-H）、PD-1/PD-L1抑制剂耐药的难治性癌症（含结直肠癌）中展现出显著疗效，疾病控制率达67%，并已获得FDA授予快速通道资格。 此外，对于免疫治疗不敏感的MSS型mCRC，癌症疫苗疗法带来了新希望。6月，Enterome公司公布了其癌症疫苗EO4010联合纳武利尤单抗±贝伐珠单抗（bevacizumab）治疗MSS/错配修复正常型mCRC的1/2期试验积极结果：联合治疗组的12个月生存率达40%，中位生存期为11.3个月，为这一传统上被视为免疫治疗“冷肿瘤”的CRC亚型提供了通过疫苗激活抗肿瘤免疫应答的新治疗策略。 自2025年以来，还有其他许多结直肠癌新药管线取得临床进展，此处不再一一列举，我们期待未来能见证更多研发成果涌现。 一体化CRDMO平台助力结直肠癌治疗持续创新 多年来，全球结直肠癌治疗领域取得了长足进步，数十种新药相继获批上市。尤其对于难治性转移性结直肠癌这一治疗选择长期受限的群体，持续涌现的创新方案为患者带来了生命延续的曙光。 尽管如此，转移性结直肠癌的治疗仍面临着肿瘤异质性高、耐药问题突出等重大挑战。目前，全球医药界正通力合作、携手攻坚，不断推动该领域向前发展。权威期刊Nature Reviews Clinical Oncology今年发表的一篇论文指出，随着更多临床试验数据的持续积累，靶向疗法已成为携带明确癌症驱动基因突变患者的重要选择。为进一步提高疗效，未来需优化现有药物及联合治疗策略，并深入探索肿瘤的耐药机制，以寻找逆转耐药的有效途径。与此同时，免疫治疗也亟待突破，有必要加强转化研究，以发现可精准预测免疫检查点抑制剂疗效的生物标志物，并开发新策略，以惠及肿瘤免疫原性较低的结直肠癌患者群体。 在推动结直肠癌治疗方案持续创新的过程中，药明康德始终致力于支持全球合作伙伴从药物研究（R）、开发（D）到商业化生产（M）各个阶段的需求，通过独特的一体化、端到端CRDMO模式，助力突破性疗法加速研发进程、早日惠及患者。在医药创新生态圈的合力下，我们坚信，更多突破性疗法将不断涌现，为结直肠癌患者带来更多新的曙光。 参考资料： [1] Colorectal Cancer. Retrieved September 8, 2025, from https://www.aacr.org/patients-caregivers/cancer/colorectal-cancer/ [2] COLORECTUM. Retrieved September 8, 2025, from https://gco.iarc.who.int/media/globocan/factsheets/cancers/41-colorectum-fact-sheet.pdf [3] What Is Colorectal Cancer? Retrieved September 8, 2025, from https://www.cancer.org/cancer/types/colon-rectal-cancer/about/what-is-colorectal-cancer.html [4] Bray, Freddie et al. “Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.” CA: a cancer journal for clinicians vol. 74,3 (2024): 229-263. doi:10.3322/caac.21834 [5] Ciracì, Paolo et al. “Late-line options for patients with metastatic colorectal cancer: a review and evidence-based algorithm.” Nature reviews. Clinical oncology vol. 22,1 (2025): 28-45. doi:10.1038/s41571-024-00965-0 [6] Pericay, Carles et al. “Real-World Outcomes in Patients with Metastatic Colorectal Cancer in Spain: The RWD-ACROSS Study.” Cancers vol. 15,18 4603. 17 Sep. 2023, doi:10.3390/cancers15184603 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号回复“转载”，获取转载须知。