Afatinib Dimaleate

一、为什么需要这份"安全指南"？ 50%的癌症患者在病程中需要接受放疗。随着靶向治疗的普及，越来越多患者同时面临一个临床难题： > "正在吃靶向药，现在需要做放疗，两者能同时进行吗？会不会毒性太大？" 这正是欧洲肿瘤内科学会（ESMO）和欧洲放射肿瘤学会（ESTRO）联合发布这份共识声明的原因。研究团队系统筛查了2745篇文献，最终纳入110项研究，通过两轮德尔菲专家共识，为57种临床场景制定了具体的安全建议。 二、核心结论：先记住这三句话 要点 说明 ⚠多数情况需谨慎 大多数联合方案可能增加毒性，需要调整 🎯三种处理策略 ①不联合②重大调整（停药/减量/改方案）③轻微/无需调整 📍因药而异、因部位而异 不同靶向药、不同放疗部位，策略完全不同 三、EGFR抑制剂：数据最充分，皮肤毒性是重点 代表药物 - 单抗类：西妥昔单抗、帕妥珠单抗、尼妥珠单抗； - 小分子TKI：吉非替尼、厄洛替尼、阿法替尼、奥希替尼等。 关键发现 - 皮肤毒性明确增加：大量高质量证据显示，联合放疗会显著增加严重皮炎、皮疹风险（主要来自头颈部肿瘤研究）。 - 奥希替尼需特别警惕：一项回顾性研究显示，奥希替尼联合胸部高剂量放疗时，放射性肺炎风险显著升高。 专家共识建议（表2核心内容） 放疗部位 低剂量姑息放疗 常规分割高剂量放疗 立体定向高剂量放疗 皮肤 轻微/无需调整 重大调整 重大调整 脑部 轻微/无需调整 重大调整 重大调整 头颈部 重大调整 重大调整 重大调整 胸部 重大调整 重大调整 重大调整 腹部/盆腔 轻微/无需调整 重大调整 重大调整 肌肉骨骼 轻微/无需调整 重大调整 重大调整 > ⚠特殊警告：奥希替尼联合胸部高剂量常规分割或立体定向放疗——建议不联合。 重要例外：西妥昔单抗联合头颈部根治性放疗是故意设计的同步方案（如Bonner研究），不适用"重大调整"建议。 四、ALK抑制剂：证据有限，保守为上 代表药物 克唑替尼、阿来替尼、布格替尼、塞瑞替尼、洛拉替尼。 关键发现 - 血脑屏障穿透差异大：克唑替尼几乎不透过血脑屏障，而新一代药物（阿来替尼、洛拉替尼）脑部浓度高； - 数据稀缺：大多数研究是回顾性、小样本，且常混合EGFR和ALK患者数据； - 个案警示：有报道显示克唑替尼联合颈椎放疗（10×3Gy）导致4级严重食管炎； 专家共识建议（表3核心内容） 放疗部位 低剂量姑息放疗 常规分割高剂量放疗 立体定向高剂量放疗 皮肤 轻微/无需调整 重大调整 重大调整 脑部 重大调整 重大调整 重大调整 头颈部 重大调整 重大调整 重大调整 胸部 重大调整 重大调整 重大调整 腹部/盆腔 重大调整 重大调整 重大调整 肌肉骨骼 轻微/无需调整 重大调整 重大调整 > 关键提示：由于新一代ALK抑制剂（如洛拉替尼）脑部穿透力强，不能简单套用克唑替尼的"安全"数据。 五、BRAF/MEK抑制剂：皮肤毒性突出，维莫非尼最"危险" 代表药物 - BRAF抑制剂：维莫非尼、达拉非尼、恩考芬尼； - MEK抑制剂：曲美替尼、Binimetinib、Cobimetinib。 关键发现 - 皮肤毒性机制特殊： - -BRAF抑制可导致paradoxical MAPK信号激活，促进角质形成细胞增殖； -- 更多细胞进入放疗敏感的M期 → 皮肤放射敏感性增加； -- 维莫非尼风险最高：即使低剂量姑息性皮肤放疗，也不建议联合； - 神经系统毒性：脑放疗联合BRAF/MEK抑制剂的数据质量参差，部分研究显示神经毒性增加，但也有研究未发现，不能排除风险。 专家共识建议（表4核心内容） 放疗部位 低剂量姑息放疗 常规分割高剂量放疗 立体定向高剂量放疗 皮肤 重大调整 不建议联合 不建议联合 脑部 重大调整 重大调整 重大调整 头颈部 重大调整 重大调整 重大调整 胸部 重大调整 重大调整 重大调整 腹部/盆腔 重大调整 重大调整 重大调整 肌肉骨骼 重大调整 重大调整 重大调整 > ⚠绝对禁忌：维莫非尼联合任何皮肤放疗（包括低剂量姑息放疗）——不建议联合。 六、什么是"重大调整"？具体怎么做 根据共识定义，重大调整包括以下策略： 药物层面 - 暂停用药：放疗前停药少于5个药物消除半衰期（通常数天），此时药物仍有活性但浓度降低； - 减量使用：临床相关剂量降低，需评估对疗效的影响； - 时机调整：放疗结束后至多1周恢复用药（如急性毒性持续则延后）。 > ⚠关键区分：如需停药≥5个半衰期（药物基本清除），则属于"不建议联合"策略，而非"重大调整"。 放疗层面 - 降低处方剂量：计划靶区（PTV）剂量降低≥20%； - 减少靶区覆盖：≥20%的PTV体积接受低剂量； - 技术优化：采用更先进的放疗技术（IMRT、VMAT、IGRT）保护正常组织。 低剂量姑息放疗的特殊性 例如，对于单次8Gy、5次4Gy等低剂量方案，由于本身毒性风险较低，部分场景可仅需轻微调整或无需调整。 七、给患者的实用建议 ✅ 应该做的 - 主动告知：向放疗科医生说明正在使用的所有靶向药物； - 询问策略：是否需要在放疗期间暂停或调整靶向药？ - 关注皮肤：EGFR和BRAF/MEK抑制剂患者，放疗期间密切观察皮肤反应； - 记录症状：出现咳嗽（胸部放疗）、腹泻（腹部放疗）、头痛（脑部放疗）及时报告。 ❌ 避免做的 - 不要自行停药：靶向药突然中断可能导致"肿瘤反跳"（tumor flare）； - 不要隐瞒用药史：包括近期用过的药物（半衰期内仍有影响）； - 不要忽视轻微症状：早期干预可避免严重毒性。 八、局限性与展望 这份共识也坦诚指出了当前证据的不足： - 研究质量参差：多数为回顾性研究，缺乏随机对照试验； - 样本量小：ALK和BRAF/MEK抑制剂的数据尤其有限； - 随访时间短：晚期毒性数据不足； - 新药滞后：文献检索截至2021年，这之后的新药数据待补充。 未来方向：建立前瞻性登记研究，开展药物-放疗联合的专门临床试验，在药物研发早期即纳入放疗相互作用评估。 九、一句话总结 > EGFR抑制剂要防皮肤，奥希替尼避开胸；ALK证据尚不足，保守处理最稳妥；BRAF/MEK皮肤毒，维莫非尼禁皮肤。 参考文献 van Aken ESM, et al. ESMO-ESTRO consensus statements on the safety of combining radiotherapy with EGFR, ALK, or BRAF/MEK inhibitors. ESMO Open. 2026;11(3):106076. > 以上内容基于近期文献与公开数据库的检索结果，供科普参考。如需在临床实际操作中使用，请结合当地实验室的标准操作流程与专业病理报告。本文代表个人观点，内容仅供参考，如有表述不当之处，还请指正。若涉及隐私或侵权请联系删除。

Topline global pivotal Phase 3 data for firmonertinib in first-line EGFR exon 20 insertion mutant NSCLC expected mid-2026 Global pivotal Phase 3 first-line PACC mutant NSCLC study for firmonertinib enrollment underway ADC pipeline advancing with first ADC program, ARR-217, in Phase 1 clinical development Cash and investments of $312.8 million as of December 31, 2025 expected to fund operations into 3Q 2027 NEWTOWN SQUARE, Pa., March 05, 2026 (GLOBE NEWSWIRE) -- ArriVent BioPharma, Inc. (Company or ArriVent) (Nasdaq: AVBP), a clinical-stage company dedicated to accelerating the global development of innovative biopharmaceutical therapeutics, today reported financial results for the year ended December 31, 2025, and highlighted recent Company progress. “We are advancing firmonertinib toward potential registration, supported by two pivotal programs targeting uncommon EGFR mutations in non-small cell lung cancer (NSCLC), a high unmet need with limited treatment options,” said Bing Yao, CEO of ArriVent. “Our robust clinical data, including CNS activity, underscores the potential of firmonertinib to become a chemotherapy-free standard of care. We look forward to topline pivotal data for firmonertinib monotherapy in frontline EGFR exon 20 insertion mutant NSCLC expected in mid-2026. This is an event driven study, so we plan to continue sharpening our timeline as we look forward to sharing our data.” Dr. Yao continued, “Our antibody-drug conjugate (ADC) portfolio is also gaining momentum, led by ARR-217, a CDH17-targeted ADC currently in an ongoing Phase 1 trial, with best-in-class potential in gastrointestinal cancers. We expect additional ADC candidates to advance toward the clinic, broadening our pipeline beyond lung cancer into multiple additional solid tumor indications. Backed by a strong balance sheet and a projected cash runway into 3Q 2027, we are well positioned to deliver on our near-term catalysts.” Recent and Full Year 2025 Highlights Firmonertinib Dosed first in patient pivotal ALPACCA study. In December 2025, ArriVent announced dosing of the first patient in the global pivotal Phase 3 ALPACCA study evaluating firmonertinib monotherapy for first-line treatment of epidermal growth factor receptor (EGFR) PACC mutant non-small cell lung cancer (NSCLC) (NCT07185997). Positive final data in EGFR PACC mutant NSCLC. In September 2025, ArriVent presented positive final proof-of-concept data from the randomized global Phase 1b FURTHER trial cohort of first-line firmonertinib monotherapy in patients with NSCLC harboring EGFR PACC mutations at the 2025 World Conference on Lung Cancer (WCLC) (NCT05364073). Firmonertinib demonstrated clinically meaningful progression free survival, central nervous system (CNS) complete responses, and a manageable safety pro with previous trials. We believe this to be the first clinical dataset testing an EGFR inhibitor in a prospectively defined population of EGFR PACC mutant NSCLC. Completed enrollment for pivotal FURVENT trial . During the first quarter of 2025, we completed enrollment in the global pivotal Phase 3 FURVENT study of firmonertinib monotherapy in first-line NSCLC EGFR exon 20 insertion mutations (NCT05607550). Firmonertinib, an oral, highly brain-penetrant, and broadly active mutation-selective EGFR inhibitor, received Food and Drug Administration (FDA) Breakthrough Therapy Designation in this patient population. Received National Medical Products Administration (NMPA) approval in China in second-line EGFR exon 20 insertion mutations. In February 2026, our partner Shanghai Allist Pharmaceutical Technology Co., Ltd., received NMPA approval for firmonertinib for adults with locally advanced or metastatic NSCLC who have progressed on or after prior platinum-based chemotherapy or who are intolerant to platinum-based chemotherapy and who have been tested for the presence of EGFR exon 20 insertion mutations. Pipeline Clinical advancement of ADC lead ARR-217 (MRG007). Ongoing Phase 1 dose escalation for ARR-217, a CDH17 targeted ADC, in gastrointestinal malignancies in partnership with Lepu Biopharma Co., Ltd. ArriVent also received FDA IND clearance for ARR-217 and dosed its first patient in March 2026. Upcoming Milestones Firmonertinib pivotal EGFR exon 20 insertions data. Top-line firmonertinib monotherapy data from the global pivotal FURVENT Phase 3 (NCT05607550) study for first-line EGFR exon 20 insertions mutant NSCLC is projected to be in mid-2026. IND filing for ARR-002. U.S. IND filing for first-in-class ADC program planned for first half 2026. Plan to present preclinical data at an upcoming conference. Complete Phase 1 dose escalation for ARR-217. Plan to complete Phase 1 dose escalation and enter into dose optimization for ARR-217, a CDH17 targeting ADC program, in the second half of 2026. 2025 Financial Results As of December 31, 2025, the Company had cash and investments of $312.8 million, which is expected to fund operations into 3Q 2027. Net cash used in operations was $160.6 million and $70.2 million for the years ended December 31, 2025 and 2024, respectively. Research and development expenses were $153.4 million and $79.0 million for the years ended December 31, 2025 and 2024, respectively. The research and development expenses in 2025 include a one-time upfront payment to Lepu Biopharma Co., Ltd. General and administrative expenses were $24.2 million and $15.3 million for the years ended December 31, 2025 and 2024, respectively. Net loss was $166.3 million and $80.5 million for the years ended December 31, 2025 and 2024, respectively. About ArriVent ArriVent is a clinical-stage biopharmaceutical company dedicated to the identification, development, and commercialization of differentiated medicines to address the unmet medical needs of patients with cancers. ArriVent seeks to utilize its team’s deep drug development experience to maximize the potential of its lead development candidate, firmonertinib, and advance a pipeline of novel therapeutics, such as next-generation antibody drug conjugates, through approval and commercialization. About Firmonertinib Firmonertinib is an oral, highly brain-penetrant, and broadly active mutation-selective epidermal growth factor receptor (EGFR) inhibitor active against both classical and uncommon EGFR mutations, including PACC and exon 20 insertion mutations. In March 2021, firmonertinib was approved in China for first-line advanced non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletion or L858R mutations and for patients with previously treated locally advanced or metastatic NSCLC with EGFR T790M mutation, otherwise known as EGFR classical mutations. Firmonertinib was granted U.S. Food and Drug Administration (FDA) Breakthrough Therapy Designation for the treatment of patients with previously untreated locally advanced or metastatic non-squamous NSCLC with EGFR exon 20 insertion mutations. Firmonertinib was also granted U.S. FDA Orphan Drug Designation for the treatment of NSCLC with EGFR mutations or human epidermal growth factor receptor 2 (HER2) mutations or HER4 mutations. Firmonertinib is currently being studied in a global Phase 3 trial for first-line NSCLC patients with EGFR exon 20 insertion mutations (FURVENT; NCT05607550) and in a global Phase 3 study in first line NSCLC patients with EGFR PACC mutations (ALPACCA; NCT07185997). About EGFR mutant NSCLC Globally, lung cancer is the leading cause of cancer-related deaths among men and women. NSCLC is the predominant subtype of lung cancer, accounting for approximately 85% of all cases. Mutational activation of the EGFR is a frequent and early event in the development of NSCLC. EGFR mutations are divided into classical and uncommon. EGFR exon 20 insertion mutations are a group of uncommon EGFR mutations and constitute approximately 9% of all EGFR mutations. PACC mutations are another group of uncommon EGFR mutations and represent approximately 12% of all EGFR mutations. Patients with NSCLC whose tumors harbor uncommon EGFR mutations have significantly lower life expectancy with available therapies and represent an area of unmet medical need. About EGFR PACC mutations P-loop and αC-helix compressing (PACC) EGFR mutations are a distinct set of approximately 70 mostly missense activating mutations within the kinase domain of EGFR. They are similar to exon 20 insertion mutations in narrowing the drug binding pocket to affect tyrosine kinase inhibitor activity. PACC mutations are diagnosed through commercially available NGS and most PCR tests. Patients with PACC mutations have limited treatment options, and there is no broadly utilized standard of care treatment for first-line PACC mutant patients. About FURVENT FURVENT is a global, pivotal 3 arm Phase 3 clinical trial of firmonertinib in first-line non-squamous locally advanced or metastatic NSCLC patients with exon 20 insertion mutations being conducted jointly with our partner Allist (NCT05607550). The FURVENT clinical trial is designed to assess the safety and efficacy of firmonertinib administered at either 160 mg or 240 mg, once-daily with each dose being compared to platinum-based chemotherapy with pemetrexed, the current first-line standard of care. The primary endpoint of this study is PFS by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Secondary endpoints in patients with brain metastases at baseline include brain-specific CNS overall response rate (CNS-ORR) and CNS-PFS by modified RECIST (mRECIST). The study enrolled 398 patients globally, including from sites in the United States, Europe and certain Asian countries including Japan and China. About ALPACCA ALPACCA is a global, pivotal 2 arm Phase 3 clinical trial of firmonertinib in first-line non-squamous locally advanced or metastatic NSCLC patients with PACC mutations being conducted jointly with our partner Allist (NCT07185997). The ALPACCA trial is evaluating firmonertinib 240 mg once daily versus investigator’s choice of osimertinib or afatinib in first-line patients with EGFR PACC mutant NSCLC. The 240 mg dose of firmonertinib was selected for pivotal development based on compelling data showing a 16-month median PFS and a confirmed 68% ORR by BICR in the FURTHER trial (NCT05364073). The primary endpoints of this study are ORR and PFS by BICR per RECIST. 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 about us and our industry that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this press release, including statements regarding our future results of operations or financial condition, business strategy and plans, cash runway, estimates of our addressable market, activity of firmonertinib compared to available therapies, anticipated clinical milestones, the timing of, and results of, top-line pivotal Phase 3 data for firmonertinib in previously untreated NSCLC patients whose tumors contain EGFR exon 20 insertion mutations, the timing of our planned enrollment of the global pivotal Phase 3 study of firmonertinib in previously untreated NSCLC patients whose tumors contain EGFR PACC mutations, the advancement of the Phase 1 study for ARR-217 in gastrointestinal tumors and the timing of presentation of data from that study, the timing of U.S. IND filing for ARR-002, and objectives of management for future operations, are forward-looking statements. In some cases, you can identify forward-looking statements because they contain words such as “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” or “would” or the negative of these words or other similar terms or expressions. Forward-looking statements are based on ArriVent’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties that are described more fully in the section titled “Risk Factors” in our annual report on Form 10-K for the fiscal year ended December 31, 2025, to be filed with the Securities and Exchange Commission on March 5, 2026 and our other filings with the Securities and Exchange Commission. Forward-looking statements contained in this press release are made as of this date, and ArriVent undertakes no duty to update such information except as required under applicable law. ARRIVENT BIOPHARMA, INC. BALANCE SHEETS (in thousands, except share and per share data) (Unaudited) December 31, 2025 2024 Assets Current assets: Cash and cash equivalents $ 45,540 $ 74,293 Short-term investments 267,281 144,570 Prepaid expenses and other current assets 20,076 8,116 Total current assets 332,897 226,979 Long-term investments — 47,683 Right of use assets – operating leases 13 154 Deferred offering costs 69 — Other assets 190 126 Total assets $ 333,169 $ 274,942 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $ 5,934 $ 3,782 Accrued expenses 19,997 13,330 Operating lease liabilities 14 162 Total current liabilities 25,945 17,274 Operating lease liabilities, net of current amount — 14 Total liabilities 25,945 17,288 Stockholders’ equity: Preferred stock $0.0001 par value, 10,000,000 shares authorized; no shares issued and outstanding — — Common stock $0.0001 par value, 200,000,000 shares authorized; 42,452,251 and 33,706,765 shares issued and outstanding at December 31, 2025 and December 31, 2024, respectively 4 3 Additional paid-in capital 711,847 496,195 Accumulated deficit (404,641 ) (238,333 ) Accumulated other comprehensive income (loss) 14 (211 ) Total stockholders’ equity 307,224 257,654 Total liabilities and stockholders’ equity $ 333,169 $ 274,942 ARRIVENT BIOPHARMA, INC. STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (in thousands, except share and per share data) (Unaudited) Year Ended December 31, 2025 2024 Operating expenses: Research and development $ 153,351 $ 79,004 General and administrative 24,183 15,304 Total operating expenses 177,534 94,308 Operating loss (177,534 ) (94,308 ) Interest and investment income 11,226 13,820 Net loss (166,308 ) (80,488 ) Unrealized gain (loss) on marketable securities 225 (211 ) Total other comprehensive gain (loss) 225 (211 ) Total comprehensive loss $ (166,083 ) $ (80,699 ) Share information: Net loss per share attributable to common stockholders, basic and diluted $ (4.32 ) $ (2.56 ) Weighted-average shares of common stock outstanding, basic and diluted 38,462,600 31,469,328 Contact: Joyce Allaire LifeSci Advisors, LLC jallaire@lifesciadvisors.com