ChiCTR2600116886 版本V1.0 版本创建时间2026/01/16 09:37:20 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2600116886 

最近更新日期：

Date of Last Refreshed on：

 2026-01-16 09:37:05 

注册时间：

Date of Registration：

 2026-01-16 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

一项在局部晚期不可切除或转移性 EGFR 突变型非鳞状细胞非小细胞肺癌患者中评价 Telisotuzumab Adizutecan 联合奥希替尼作为一线治疗的安全性、有效性和最佳剂量的 II/III 期随机研究

Public title：

A Phase 2/3 Randomized Study to Evaluate the Safety, Efficacy, and Optimal Dose of Telisotuzumab Adizutecan in Combination with Osimertinib as First-Line Treatment in Patients with Locally Advanced Unresectable or Metastatic EGFR-Mutated Non-Squamous Non-Small Cell Lung Cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

一项在局部晚期不可切除或转移性 EGFR 突变型非鳞状细胞非小细胞肺癌患者中评价 Telisotuzumab Adizutecan 联合奥希替尼作为一线治疗的安全性、有效性和最佳剂量的 II/III 期随机研究

Scientific title：

A Phase 2/3 Randomized Study to Evaluate the Safety, Efficacy, and Optimal Dose of Telisotuzumab Adizutecan in Combination with Osimertinib as First-Line Treatment in Patients with Locally Advanced Unresectable or Metastatic EGFR-Mutated Non-Squamous Non-Small Cell Lung Cancer

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

霍焕芝 

研究负责人：

李子明 

Applicant：

Huohuanzhi 

Study leader：

Ziming Li 

申请注册联系人电话：

Applicant telephone：

 +86 10 5706 1719

研究负责人电话：

Study leader's
telephone：

+86 21 62821990

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

 huanzhi.huo@abbvie.com

研究负责人电子邮件：

Study leader's E-mail：

 liziming1980@163.com

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

北京市朝阳区建国路79号2座办公楼5层；邮编100022

研究负责人通讯地址：

上海市徐汇区淮海西路241号

Applicant address：

5F, Building 2, No. 79 Jianguo Road, Chaoyang District, Beijing, China; Zip code 100022 ：

Study leader's address：

No. 241, Huaihai West Road, Xuhui District, Shanghai

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

艾伯维医药贸易（上海）有限公司

Applicant's institution：

AbbVie Pharmaceutical Trading (Shanghai) Co., Ltd

研究负责人所在单位：

上海市胸科医院

Affiliation of the Leader：

Shanghai Chest?Hospital

是否获伦理委员会批准：

是

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

 LS25127

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

上海市胸科医院伦理委员会

Name of the ethic committee：

Ehtics Committee of Shanghai Chest Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2025-10-27 00:00:00

伦理委员会联系人：

陈仲林

Contact Name of the ethic committee：

Chen Zhonglin

伦理委员会联系地址：

上海市徐汇区淮海西路241号

Contact Address of the ethic committee：

No. 241, Huaihai West Road, Xuhui District, Shanghai

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 21 22200000

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 chestgcp@126.com

研究实施负责（组长）单位：

上海市胸科医院

Primary sponsor：

Shanghai Chest?Hospital

研究实施负责（组长）单位地址：

上海市徐汇区淮海西路241号

Primary sponsor's address：

No. 241, Huaihai West Road, Xuhui District, Shanghai

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

上海市

市(区县)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

上海市胸科医院

具体地址：

上海市徐汇区淮海西路241号

Institution
hospital：

Shanghai Chest?Hospital

Address：

No. 241, Huaihai West Road, Xuhui District, Shanghai

经费或物资来源：

艾伯维医药贸易（上海）有限公司

Source(s) of funding：

AbbVie Pharmaceutical Trading (Shanghai) Co., Ltd

研究疾病：

局部晚期不可切除或转移性 EGFR 突变型非鳞状细胞非小细胞肺癌患者  

Target disease：

Patients with locally advanced unresectable or metastatic EGFR mutant non squamous cell non-small cell lung cancer

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 II-III期临床试验 

Study phase：

2-3

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

II 期 ● 评价 telisotuzumab adizutecan 联合奥希替尼的安全性和耐受性 ● 优化并选择 telisotuzumab adizutecan 与奥希替尼联合给药的III 期推荐剂量 ● 通过客观缓解率（ORR）评价 telisotuzumab adizutecan 联合奥希替尼的有效性 III期 ● 证明在盲态独立中心审查委员会（BICR）评估的无进展生存期（PFS）方面，telisotuzumab adizutecan 联合奥希替尼的有效性优于标准治疗 研究目的的具体描述： 本研究一方面是为了优化 telisotuzumab adizutecan 与奥希替尼联合给药的 RP3D，另一方面则是验证以下假设：在既往未经治疗的局部晚期或转移性 EGFR 突变型NSCLC 受试者中，telisotuzumab adizutecan 联合奥希替尼可安全给药，并且与奥希替尼或标准治疗相比能够延长临床结局。  

Objectives of Study：

Phase II ● optimize and select the phase III recommended dose of telisotuzumab adizuecan combined with osimertinib ● evaluate the effectiveness of telisotuzumab adizutecan combined with osimertinib by objective response rate (ORR) Phase III ● demonstrated the effectiveness of telisotuzumab adizutecan plus osimertinib over standard therapy in terms of progression free survival (PFS) assessed by the blinded independent central review board (BICR) Specific description of research purpose: on the one hand, this study is to optimize the rp3d of telisotuzumab adizutecan combined with osimertinib, on the other hand, it is to test the following hypothesis: in previously untreated subjects with locally advanced or metastatic EGFR mutant NSCLC, telisotuzumab adizutecan combined with osimertinib can be safely administered, and can prolong the clinical outcome compared with osimertinib or standard treatment.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1.在开始任何筛选或研究特定程序之前，受试者或其法定代理人必须自愿在经IEC/IRB 批准的知情同意书上签字并注明日期。
2.年满 18 岁的成人（或当地法规规定的可接受年龄，以较年长者为准）。
3.愿意并能够遵守本方案规定的程序。
4.筛选期间以及第 1 周期第 1 天研究治疗给药前，美国东部肿瘤协作组（ECOG）体能状态（PS）评分为 0 或 1 分。
5.筛选期间以及第 1 周期第 1 天研究治疗给药前，实验室检查值符合以下标准： ● 第 1 周期第 1 天给药前 7 d 内血清 ALT 和 AST≤3.0×ULN； ● 对于肝转移受试者：AST 和 ALT≤5.0×ULN； ● 基于 CKD-EPI 公式计算的估计肾小球滤过率（eGFR）≥30 mL/min（第 16节，附录 D）； ● 第 1 周期第 1 天给药前 7 d 内总胆红素≤1.5×ULN（如果记录证实受试者患有 Gilbert 综合征，则总胆红素≤3×ULN）； ● 第 1 周期第 1 天给药前 10 d 内中性粒细胞绝对计数（ANC）≥1,500/μL 且未使用 G-CSF； ● 第 1 周期第 1 天给药前 14 d 内血小板计数≥100,000/μL 且未输注血小板； ● 血红蛋白≥9 g/dL（第 1 周期第 1 天给药前 14 d 内未输注 RBC）； ● 白蛋白≥3 g/dL。
6.受试者不得被监禁，且必须自愿并能够提供知情同意。无法自愿提供知情同意的受试者包括一些受法律保护（例如，被监护人/被保佐人）或无法表达意愿的成人以及部分接受精神病治疗的成人。由研究者酌情决定此类患者是否可入组。
7.所有受试者必须同意在筛选期间提供近期采集的 FFPE 肿瘤组织（最好在局部晚期或转移性疾病诊断期间或之后采集）或存档组织，用于 c-Met IHC 检测和研究分层。只有获知 c-Met IHC 检测结果后方可进行随机分组（剂量优化队列）。 疾病/病症活动度；
8.既往未接受过针对局部晚期和/或转移性疾病的 EGFR TKI 治疗（C1D1 前允许参加 研究的情况除外）。对于既往接受过 EGFR TKI 辅助治疗的受试者，只要在第 1 周期第 1 天前已停药≥12 个月（例如，自奥希替尼辅助治疗末次给药以来），则允许入组。
9.根据 RECIST 第 1.1 版，受试者必须至少有一个未接受过放疗的可测量病灶。若仅有一个可测量病灶，只要既往未接受过放疗且在基线肿瘤评估扫描前 14 d 内未进行活检，则可使用其作为靶病灶。
10.患有经组织学或细胞学证实的转移性/局部晚期非鳞状细胞 NSCLC，并且 CLIA 认证的实验室（美国研究中心）或官方认可的当地实验室（美国以外地区的研究中心）根据研究中心标准治疗，采用 FDA 批准或其他经验证的检测方法评估为EGFR 外显子 19 缺失突变或外显子 21 L858R 突变，伴或不伴其他 EGFR 突变。受试者病历中必须提供记录 EGFR 突变的检测报告副本。
11.记录显示病毒性肝炎状态，并通过筛选 HBV 和 HCV 血清学检查证实。 ● HBV 血清学检查：HBsAg、乙型肝炎表面抗体、总 HBcAb；如果患者在筛选时 HBsAg、HBsAb 和/或 HBcAb 检测呈阳性，则应在筛选时进行 HBV DNA 检测。若检出 HBV DNA（≥10 IU/mL 或高于检测限），受试者必须同意在研究治疗首次给药前至少 14 d 开始抗 HBV 治疗（根据当地标准治疗），并且愿意在研究期间和研究治疗末次给药后至少 6 个月内继续接受治疗。 ● HCV 血清学检查：HCV 抗体和 HCV RNA（如果抗体检测呈阳性）；如果受试者的 HCV 抗体检测结果呈阳性，还必须进行 HCV RNA 检测，以确定该患者是否存在妨碍入组的活动性 HCV 感染。 ● 如果 HBV 感染受试者符合以下标准，则允许入组：研究治疗开始前 35 d 内测定的 HBV DNA<500 IU/mL，且在研究治疗首次给药前至少 14 d 开始抗HBV 治疗（根据当地标准治疗），并愿意在研究期间和研究治疗末次给药后至少 6 个月内继续接受治疗。应慎用包含强效 CYP3A 抑制剂且需要持续使用的抗病毒治疗，并由研究者酌情评估是否存在不良药物-药物相互作用的潜在风险。 ● HBV 感染已痊愈（HBsAg 阴性，HBcAb 阳性）的受试者如果愿意在研究治疗期间依从 HBV DNA 监测，并同意在检出 HBV DNA（≥10 IU/mL 或高于检测限）时开始抗病毒治疗，则允许入组。 ● 已接种完整系列乙型肝炎疫苗且在筛选时 HBcAb 阴性、HBsAg 阴性和HBsAb 阳性的受试者无需在筛选时或研究期间接受 HBV DNA 监测，当地明令要求的情况除外。
12.如果感染 HIV 的受试者符合以下标准，则可入组本研究： ● CD4 计数≥100 个细胞/μL（如果 CD4 计数<200 个细胞/μL，则要求CD4/CD8 比值>0.4）。受试者已接受有效的抗逆转录病毒治疗至少 4 周，HIV 病毒载量低于 200 拷贝/mL，且受试者未发生归因于 ART 的>1 级症状性 AE。 ● 应慎用包含强效 CYP3A 抑制剂且需要持续使用的抗逆转录病毒治疗，并由研究者酌情评估是否存在不良药物-药物相互作用的潜在风险。
13.既往全身性抗肿瘤治疗引起的任何毒性必须消退至 CTCAE 1 级或基线水平（脱发[任何级别]或≤2 级外周神经病变除外）。
14.受试者不存在任何重大、危及生命的疾病，且研究者判断预期寿命至少为 3 个月。 避孕；
15.有生育能力的女性受试者需要进行妊娠试验： ● 受试者在筛选访视时的血清妊娠试验结果必须为阴性，在任何研究治疗首次给药前（包括奥希替尼给药前）的基线尿妊娠试验结果也必须为阴性。 ● 筛选时血清妊娠试验结果不明确的受试者不得存在临床怀疑妊娠的情况或导致不明确结果的其他病理学原因，且必须在≥3 d 后再次进行血清妊娠试验，以证实持续非阳性结果（除非当地要求禁止纳入妊娠试验结果不明确的受试者）。 ● 基线时尿妊娠试验结果不明确或不确定的受试者必须进行血清妊娠试验。出现此类情况时，如果血清妊娠试验结果为阳性，则受试者不得入组本研究。
16.有生育能力的女性受试者必须从研究治疗开始直至研究治疗（包括 telisotuzumab adizutecan）末次给药后至少 250 d 内采取至少 1 种方案规定的避孕措施。无生育能力的女性受试者无需采取避孕措施。奥希替尼单药治疗组的女性受试者应遵循现行奥希替尼说明书规定。
17.女 性 受 试 者 未 处 于 妊 娠 期 或 哺 乳 期 ， 且 在 研 究 期 间 或 研 究 治 疗 （ 包 括 telisotuzumab adizutecan）末次给药后约 250 d 内无备孕或捐卵计划。奥希替尼单药治疗组的女性受试者应遵循现行奥希替尼说明书规定。
18.有生育能力的女性伴侣保持活跃性生活的男性受试者必须同意从研究治疗开始直至研究治疗末次给药后 160 d 内采取方案规定的避孕措施。奥希替尼单药治疗组的女性受试者应遵循现行奥希替尼说明书规定。
19.男性受试者在研究期间或研究治疗（包括 telisotuzumab adizutecan）末次给药后约160 d 内无备孕或捐精计划。奥希替尼单药治疗组的男性受试者应遵循现行奥希替尼说明书规定。

Inclusion criteria

1.Before starting any screening or research specific procedure, the subject or their legal representative must voluntarily sign and date the IEC/IRB approved informed consent form; 2. Adults who are over 18 years old (or the acceptable age specified by local regulations, whichever is older); 3. Willing and able to comply with the procedures stipulated in this plan; 4.During the screening period and on the first day of the first cycle before treatment administration, the physical fitness status (PS) score of the Eastern Cooperative Oncology Group (ECOG) in the United States was 0 or 1; 5.During the screening period and on the first day of the first cycle before administering the study treatment, laboratory test values meet the following criteria: ●Within 7 days before administration on the first day of the first cycle, serum ALT and AST levels should be <= 3.0 × ULN; ●For subjects with liver metastasis: AST and ALT <= 5.0 × ULN; ●Estimated glomerular filtration rate (eGFR) based on CKD-EPI formula >= 30 mL/min (Section 16, Appendix D); ●Total bilirubin <= 1.5 × ULN within 7 days before administration on the first day of the first cycle (if the record confirms that the subject has Gilbert syndrome, total bilirubin <= 3 × ULN); ●Within 10 days before administration on the first day of the first cycle, the absolute neutrophil count (ANC) was >= 1500/μ L and G-CSF was not used; ●Platelet count >= 100000/μ L and no platelet transfusion within 14 days before administration on the first day of the first cycle; ●Hemoglobin >= 9 g/dL (RBC not infused within 14 days before administration on the first day of the first cycle); ●Albumin >= 3 g/dL. 6. Participants must not be imprisoned and must voluntarily and be able to provide informed consent. Subjects who are unable to voluntarily provide informed consent include some adults who are protected by law (such as those under guardianship/assistance) or unable to express their wishes, as well as some adults receiving psychiatric treatment. At the discretion of the researchers, such patients may be included in the study; 7. All subjects must agree to provide recently collected FFPE tumor tissue (preferably collected during or after local late stage or metastatic disease diagnosis) or archived tissue for c-Met IHC detection and study stratification during the screening period. Random grouping (dose optimization queue) can only be performed after obtaining the c-Met IHC test results. Disease/illness activity level; 8. Have not received EGFR TKI treatment for locally advanced and/or metastatic diseases in the past (allowed to participate before C1D1)Except for research cases. For subjects who have previously received EGFR TKI adjuvant therapy, as long as the medication has been discontinued for ≥ 12 months before the first day of the first cycle (e.g. since the last administration of osimertinib adjuvant therapy), they are allowed to be enrolled; 9.According to RECIST version 1.1, subjects must have at least one measurable lesion that has not received radiation therapy. If there is only one measurable lesion, as long as it has not received radiation therapy in the past and has not undergone biopsy within 14 days before the baseline tumor assessment scan, it can be used as the target lesion; 10. Suffering from metastatic/locally advanced non squamous cell NSCLC confirmed by histology or cytology, and treated according to the standards of the CLIA accredited laboratory (US research center) or officially recognized local laboratory (research center outside the US), evaluated as EGFR exon 19 deletion mutation or exon 21 L858R mutation with or without other EGFR mutations using FDA approved or other validated testing methods. A copy of the EGFR mutation test report must be provided in the subject's medical record; 11. Record the status of viral hepatitis and confirm it through screening for HBV and HCV serological tests. ●HBV serological test: HBsAg, hepatitis B surface antibody, total HBcAb; If patients test positive for HBsAg, HBsAb, and/or HBcAb during screening, HBV DNA testing should be performed during screening. If HBV DNA is detected (>= 10 IU/mL or above the detection limit), the subject must agree to begin anti HBV treatment (according to local standards) at least 14 days before the first dose of study treatment, and be willing to continue treatment during the study period and for at least 6 months after the last dose of study treatment. ●HCV serological test: HCV antibodies and HCV RNA (if antibody test positive); If the subject's HCV antibody test result is positive, HCV RNA testing must also be performed to determine whether the patient has active HCV infection that hinders enrollment. ●If HBV infected subjects meet the following criteria, they are allowed to be enrolled: HBV DNA<500 IU/mL measured within 35 days before the start of study treatment, and have started anti HBV treatment (according to local standards) at least 14 days before the first dose of study treatment, and are willing to continue treatment during the study period and for at least 6 months after the last dose of study treatment. Antiviral therapy containing potent CYP3A inhibitors and requiring continued use should be used with caution, and potential risks of adverse drug drug interactions should be evaluated by the researcher at their discretion. ●Subjects who have recovered from HBV infection (HBsAg negative, HBcAb positive) and are willing to comply with HBV DNA monitoring during the study treatment period, and agree to start antiviral therapy when HBV DNA is detected (>= 10 IU/mL or above the detection limit), are allowed to be enrolled. ●Subjects who have received the complete series of hepatitis B vaccines and are HBcAb negative, HBsAg negative, or HBsAb positive during screening are not required to undergo HBV DNA monitoring during screening or the study period, except as required by local regulations; 12.If HIV infected subjects meet the following criteria, they can be enrolled in this study: ●CD4 count >= 100 cells/μ L (if CD4 count<200 cells/μ L, CD4/CD8 ratio>0.4 is required). The subject has received effective antiretroviral therapy for at least 4 weeks, with an HIV viral load below 200 copies/mL, and has not experienced grade 1 symptomatic adverse events attributed to ART.;●Antiretroviral therapy containing potent CYP3A inhibitors and requiring continuous use should be used with caution, and potential risks of adverse drug drug interactions should be evaluated by the researcher at their discretion; 13. Any toxicity caused by previous systemic anti-tumor therapy must subside to CTCAE grade 1 or baseline levels (except for hair loss [of any grade] or peripheral neuropathy <= grade 2); 14. The subjects do not have any major or life-threatening illnesses, and the researchers estimate a life expectancy of at least 3 months. contraception; 15. Female subjects with fertility need to undergo pregnancy tests: ●The serum pregnancy test results of the subjects during the screening visit must be negative, and the baseline urine pregnancy test results before the first administration of any study treatment (including before the administration of osimertinib) must also be negative. ●Subjects with unclear serum pregnancy test results during screening must not have clinical suspicion of pregnancy or other pathological reasons leading to unclear results, and must undergo serum pregnancy test again after >= 3 days to confirm continued non positive results (unless local requirements prohibit the inclusion of subjects with unclear pregnancy test results). ●Subjects whose urine pregnancy test results are unclear or uncertain at baseline must undergo a serum pregnancy test. When such a situation occurs, if the serum pregnancy test result is positive, the subject shall not be enrolled in this study; 16. Female subjects with fertility must adopt at least one contraceptive measure specified in the study protocol from the start of study treatment until at least 250 days after the last dose of study treatment (including telisotuzumab adizutecan). Female subjects without fertility do not need to take contraceptive measures. Female subjects in the monotherapy group of osimertinib should follow the current instructions for osimertinib; 17. Female participants who are not in pregnancy or lactation and have not undergone the study period or study treatment (including There is no plan to conceive or donate eggs within approximately 250 days after the last administration of telisotuzumab adizutecan. Female subjects in the monotherapy group of osimertinib should follow the current instructions for osimertinib; 18. Male participants who maintain active sexual activity with a female partner who is capable of reproduction must agree to use the contraceptive measures specified in the protocol from the start of study treatment until 160 days after the last dose of study treatment. Female subjects in the monotherapy group of osimertinib should follow the current instructions for osimertinib; 19.During the study period or approximately 160 days after the last dose of study treatment (including telisotuzumab adizutecan), male subjects had no plans to conceive or donate sperm. Male subjects in the monotherapy group of osimertinib should follow the current instructions for osimertinib.

排除标准：

1.存在需要全身性激素治疗的间质性肺疾病（ILD）、肺部非感染性炎症病史，或 筛选时胸部 CT 扫描提示任何活动性 ILD/肺部非感染性炎症证据。
2.存在特发性肺纤维化、机化性肺炎（例如，闭塞性细支气管炎）、药物性肺部炎 症或特发性肺部炎症病史。
3.存在有临床意义（根据研究者评估）的伴随肺特异性疾病史，包括但不限于： ● 基础肺部疾病（即，肺栓塞[研究入组前 3 个月内]、重度哮喘、重度COPD、限制性肺疾病、胸腔积液、依赖辅助供氧等）。 ● 筛选时存在任何自身免疫性疾病、结缔组织病或炎性疾病，伴有经证实或疑似肺部受累（即，类风湿性关节炎、舍格林综合征、肉状瘤病等），以及既往接受过全肺切除术。
4.已知存在活动性/症状性 CNS 转移和/或癌性脑膜炎。既往接受过脑转移治疗的受试者允许入组，前提是成像复查显示影像学稳定（即，无进展证据）至少 4 周（注：成像复查应在 C1D1 前进行），临床稳定且在研究治疗首次给药前至少 14d 内无需激素治疗。对于无症状的脑转移受试者，若研究者判断无需根治性治疗，则允许入组。不允许在研究治疗前 14 d 内进行 CNS 转移放疗。
5.受试者患有软脑膜疾病，或受试者存在脊髓压迫且无法通过手术或放疗根治。
6.任何恶性肿瘤病史，但接受过根治性治疗、研究治疗首次给药前 2 年内无已知活动性疾病且研究者判断复发风险低的恶性肿瘤、成功治疗的非黑色素瘤皮肤癌或局部宫颈原位癌除外。
7.过去 6 个月内存在有临床意义（研究者自行判断）的药物或酒精滥用史。
8.存在可能干扰药物吸收的疾病，包括但不限于短肠综合征。
9.存在有临床意义的疾病史，或研究者判断会干扰受试者参加本研究或导致受试者不适合接受研究治疗的任何其他原因。
10.在任何研究治疗前 28 d 内接受过大手术或出现严重的外伤性损伤，或预计在研究干预过程中需要进行大手术。研究治疗前 28 d 内植入血管通路装置或进行肿瘤活检的受试者允许入组。
11.存在难治性恶心和呕吐、慢性胃肠道疾病、无法吞咽药物制剂或既往接受过重大肠道切除术等妨碍奥希替尼充分吸收的情况。
12.曾对研究药物（及其辅料）和/或其他同类产品的成分产生过敏反应或显著敏感。
13.受试者不得存在有临床意义的疾病，包括但不限于： 有临床意义的心脏疾病，包括： ● 在研究药物首次给药前 1 年内发生心肌梗死或 6 个月内发生卒中，或存在与心脏功能相关或影响心脏功能的不稳定或未控制的疾病/状况（例如，不稳定型心绞痛、充血性心力衰竭、纽约心脏协会 III-IV 级）、心律失常（NCI CTCAE 2 级或以上）。患者存在任何可能增加 QTc 延长风险或心律失常事件风险的因素，例如电解质异常，包括： ● 血清/血浆钾<正常值下限（LLN） ● 血清/血浆镁<正常值下限（LLN） ● 血清/血浆钙<正常值下限（LLN） ● 根据筛选时的 3 次心电图（ECG）并使用筛选诊室心电图仪推导 QTc 值，测得的平均静息校正 QT 间期（QTc）>470 ms。 ● 任何有临床意义的静息 ECG 节律、传导或形态异常，例如完全左束支阻滞、三度心传导阻滞和二度心传导阻滞。心力衰竭、先天性长 QT 综合征、长 QT 综合征家族史或一级亲属 40 岁以下不明原因猝死，或者使用任何已知可延长 QT 间期并导致尖端扭转型室性心动过速的合并用药。 ● 通过筛选超声心动图（ECHO）或多门控采集（MUGA）扫描评估的基线LVEF 低于正常值下限（LLN）。
14.对于不适合根治性手术或放疗的晚期 NSCLC 患者，既往接受过任何全身性抗治肿瘤治疗，包括化疗、生物治疗、免疫治疗或任何试验性药物。既往接受过辅助和新辅助治疗（化疗、放疗、免疫治疗、生物治疗、试验性药物）或根治性放疗/放化疗，伴或不伴免疫治疗、生物治疗、试验性药物等治疗方案的患者允许入组，前提是在疾病复发前至少 12 个月已结束治疗。
15.受试者在研究治疗首次给药前 7 d 内不得使用已知的全身性强效 CYP3A 抑制剂（仅适用于 II 期剂量递增受试者）。研究期间如有临床指征，可谨慎使用强效CYP3A 抑制剂。强效 CYP3A 抑制剂的更多详细信息和示例见表 4，第 5.3 节。
16.存在需要全身性治疗的活动性感染。
17.受试者在任何研究治疗首次给药前 7 d 内接种过任何活疫苗。

Exclusion criteria：

1. There is a history of interstitial lung disease (ILD) requiring systemic hormone therapy, non infectious inflammation of the lungs, or Chest CT scan during screening suggests any evidence of active ILD/non infectious inflammation in the lungs; 2. Presence of idiopathic pulmonary fibrosis, organizing pneumonia (such as bronchiolitis obliterans), and drug-induced pulmonary inflammation History of symptoms or idiopathic pulmonary inflammation; 3. There is a clinically significant (according to the researcher's assessment) history of accompanying lung specific diseases, including but not limited to: ● Basic pulmonary diseases (i.e. pulmonary embolism [within 3 months prior to enrollment], severe asthma, severe COPD, restrictive pulmonary disease, pleural effusion, dependence on auxiliary oxygen supply, etc.). ●During screening, there may be any autoimmune disease, connective tissue disease, or inflammatory disease, accompanied by confirmed or suspected lung involvement (i.e. rheumatoid arthritis, Sjogren's syndrome, sarcomatosis, etc.), as well as a history of total lung resection; 4. It is known that there is active/symptomatic CNS metastasis and/or cancerous meningitis. Subjects who have received previous treatment for brain metastases are allowed to be enrolled, provided that imaging review shows imaging stability (i.e., no evidence of progression) for at least 4 weeks (note: imaging review should be conducted before C1D1), clinical stability, and no need for hormone therapy for at least 14 days prior to the first dose of study treatment. For asymptomatic subjects with brain metastases, if the researcher determines that curative treatment is not necessary, they are allowed to be enrolled. CNS metastasis radiotherapy is not allowed within 14 days before the study treatment; 5. The subject has leptomeningeal disease or spinal cord compression that cannot be cured by surgery or radiation therapy; 6. Any history of malignant tumors, except for malignant tumors that have received curative treatment, have no known active disease within 2 years before the first administration of the study treatment, and have a low risk of recurrence as determined by the researcher, as well as successfully treated non melanoma skin cancer or local cervical carcinoma in situ; 7. There has been a clinically significant (at the discretion of the researcher) history of drug or alcohol abuse within the past 6 months; 8. There are diseases that may interfere with drug absorption, including but not limited to short bowel syndrome; 9. There is a clinically significant history of disease, or any other reason that the researcher determines may interfere with the subject's participation in this study or make the subject unsuitable for receiving study treatment; 10. Have undergone major surgery or suffered severe traumatic injury within 28 days prior to any study treatment, or are expected to require major surgery during the study intervention process. Subjects who undergo vascular access device implantation or tumor biopsy within 28 days prior to treatment are allowed to be enrolled; 11. There are conditions that hinder the full absorption of osimertinib, such as intractable nausea and vomiting, chronic gastrointestinal diseases, inability to swallow drug preparations, or previous major intestinal resection surgery; 12. Have experienced allergic reactions or significant sensitivity to the ingredients of research drugs (and their excipients) and/or other similar products; 13. The subjects shall not have clinically significant diseases, including but not limited to: Clinically significant heart diseases, including: ●Within 1 year prior to the first administration of the investigational drug, a myocardial infarction or stroke occurs within 6 months, or there is an unstable or uncontrolled disease/condition related to or affecting cardiac function (such as unstable angina, congestive heart failure, New York Heart Association III-IV grade), arrhythmia (NCI CTCAE grade 2 or above). The patient has any factors that may increase the risk of QTc prolongation or arrhythmia events, such as electrolyte abnormalities,including: ●Serum/plasma potassium levels are below the lower limit of normal (LLN) ●Serum/plasma magnesium470 ms. ●Any clinically significant resting ECG rhythm, conduction, or morphological abnormalities, such as complete left bundle branch block, third degree heart block, and second degree heart block. Heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death of a first-degree relative under the age of 40, or the use of any combination medication known to prolong the QT interval and cause apical torsion type ventricular tachycardia. ●LVEF evaluated by screening echocardiography (ECHO) or multi gated acquisition (MUGA) scans is below the lower limit of normal (LLN); 14. For advanced NSCLC patients who are not suitable for curative surgery or radiotherapy, they have received any systemic anti-tumor treatment in the past, including chemotherapy, biotherapy, immunotherapy, or any experimental drugs. Patients who have previously received adjuvant and neoadjuvant therapy (chemotherapy, radiotherapy, immunotherapy, biologic therapy, experimental drugs) or curative radiotherapy/radiochemotherapy, with or without immunotherapy, biologic therapy, experimental drugs, etc., are allowed to be enrolled, provided that treatment has ended at least 12 months before disease recurrence; 15. Subjects are not allowed to use known systemic potent CYP3A inhibitors (only applicable to phase II dose escalation subjects) within 7 days prior to the first administration of the study treatment. If there are clinical indications during the study period, caution should be exercised when using potent CYP3A inhibitors. More detailed information and examples of potent CYP3A inhibitors can be found in Table 4, Section 5.3; 16. There is an active infection that requires systemic treatment; 17. The subject has received any live vaccine within 7 days prior to the first administration of any study treatment.

研究实施时间：

Study execute time：

从 From 2026-01-31 00:00:00至 To 2032-10-12 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2026-01-31 00:00:00 至 To 2031-01-31 00:00:00

干预措施：

Interventions：

组别：

第一阶段2期：telisotuzumab adizutecan 2.4 mg/kg Q3W+奥希替尼

样本量：

 47

Group：

Phase 1 phase 2: telisotuzumab adizutecan 2.4 mg/kg Q3W plus osimertinib

Sample size：

干预措施：

telisotuzumab adizutecan 2.4 mg/kg Q3W+奥希替尼

干预措施代码：

Intervention：

telisotuzumab adizutecan 2.4 mg/kg Q3W plus osimertinib

Intervention code：

组别：

telisotuzumab adizutecan（最佳剂量）联合奥希替尼

样本量：

 250

Group：

telisotuzumab adizutecan (optimal dose) plus osimertinib

Sample size：

干预措施：

telisotuzumab adizutecan（最佳剂量）联合奥希替尼

干预措施代码：

Intervention：

telisotuzumab adizutecan (optimal dose) plus osimertinib

Intervention code：

组别：

第一阶段2期：telisotuzumab adizutecan 1.6 mg/kg Q3W+奥希替尼

样本量：

 47

Group：

Phase 1 phase 2: telisotuzumab adizutecan 1.6 mg/kg Q3W plus osimertinib

Sample size：

干预措施：

telisotuzumab adizutecan 1.6 mg/kg Q3W+奥希替尼

干预措施代码：

Intervention：

telisotuzumab adizutecan 1.6 mg/kg Q3W plus osimertinib

Intervention code：

组别：

第一阶段2期：奥希替尼单药

样本量：

 47

Group：

Phase 1 Phase 2: Osimertinib monotherapy

Sample size：

干预措施：

奥希替尼单药

干预措施代码：

Intervention：

Osimertinib monotherapy

Intervention code：

组别：

对照组-标准治疗（SOC）

样本量：

 250

Group：

Stand of Care (SOC)

Sample size：

干预措施：

标准治疗（SOC）

干预措施代码：

Intervention：

Stand of Care (SOC)

Intervention code：

组别：

第一阶段2期：telisotuzumab adizutecan 2.0 mg/kg Q3W+奥希替尼

样本量：

 47

Group：

Phase 1 Phase 2: telisotuzumab adizutecan 2.0 mg/kg Q3W+ osimertinib

Sample size：

干预措施：

telisotuzumab adizutecan 2.0 mg/kg Q3W+奥希替尼

干预措施代码：

Intervention：

Phase 1 Phase 2: telisotuzumab adizutecan 2.0 mg/kg Q3W+ osimertinib

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 上海市 

市(区县)：

  

Country：

China

Province：

Shanghai

City：

单位(医院)：

 上海市胸科医院 

单位级别：

 三级甲等 

Institution
hospital：

Shanghai Chest?Hospital

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 北京市 

市(区县)：

  

Country：

China

Province：

Beijing

City：

单位(医院)：

 中国医学科学院肿瘤医院 

单位级别：

 三级甲等 

Institution
hospital：

Cancer Hospital Chinese Academy of Medical Sciences

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 四川省 

市(区县)：

  

Country：

China

Province：

Sichuan

City：

单位(医院)：

 四川大学华西医院 

单位级别：

 三级甲等 

Institution
hospital：

West China Hospital of Sichuan University

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 江西省 

市(区县)：

  

Country：

China

Province：

Jiangxi

City：

单位(医院)：

 南昌大学第一附属医院 

单位级别：

 三级甲等 

Institution
hospital：

The first affiliated hostipal of nanchang university

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 广东省 

市(区县)：

  

Country：

China

Province：

Guangdong

City：

单位(医院)：

 广州医科大学附属第一医院 

单位级别：

 三级甲等 

Institution
hospital：

The First Affiliated Hospital of Guangzhou Medical University

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 湖北省 

市(区县)：

  

Country：

China

Province：

Hubei

City：

单位(医院)：

 华中科技大学同济医学院附属协和医院 

单位级别：

 三级甲等 

Institution
hospital：

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

客观缓解率 （ORR）（Ⅱ期）

指标类型：

主要指标

Outcome：

Objective response rate (ORR)

Type：

Primary indicator

测量时间点：

测量方法：

测量方法：RECIST v1.1

Measure time point of outcome：

Measure method：

RECIST v1.1

指标中文名：

无进展生存期PFS（Ⅱ期）

指标类型：

次要指标

Outcome：

Progression free survival (Phase II)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

无进展生存期（PFS）(Ⅲ期）

指标类型：

主要指标

Outcome：

Progression free survival (PFS) (Phase III)

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

反应持续时间DoR（Ⅱ期）

指标类型：

次要指标

Outcome：

Duration of Response (DoR) (Phase II)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

疾病控制率DCR（Ⅱ期）

指标类型：

次要指标

Outcome：

Disease control rate DCR (phase II)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

总体生存期OS（Ⅱ期）

指标类型：

次要指标

Outcome：

Overall survival OS (Phase II)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

总体生存期OS（Ⅲ期）

指标类型：

次要指标

Outcome：

Overall survival OS (Phase III)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

客观反应率OR、反应持续时间DOR、疾病控制率DCR（Ⅲ期）

指标类型：

次要指标

Outcome：

Objective response rate or, duration of response dor, disease control rate DCR (Phase III)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

PRO评估：身体功能相对于基线的变化、肺癌症状相对于基线的变化、 GHS/QoL相对于基线的变化。（Ⅲ期）

指标类型：

次要指标

Outcome：

PRO assessment: changes in physical function from baseline, lung cancer symptoms from baseline, and ghs/qol from baseline. (Phase Ⅲ)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

血液

组织：

Sample Name：

Blood

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

标本中文名：

肿瘤组织

组织：

Sample Name：

Tumor tissue

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

在筛选访视时，通过 IRT 为每例受试者分配唯一的鉴认代码。对于重新筛选的受 试者，应使用初始筛选访视时 IRT 分配的筛选编号。在受试者随机分组前，申办者审查入组前筛选数据以确认合格性。若受试者符合研究遴选标准按照随机化方案，使用 IRT 为受试者分配一个随机化编号，用于编码受试者的治疗组分配。

Randomization Procedure (please state who generates the random number sequence and by what method)：

During screening visits, a unique identification code is assigned to each subject through IRT. For the re filtered recipients Participants should use the screening number assigned by the IRT during the initial screening visit. Prior to randomization of subjects, the sponsor reviews the pre enrollment screening data to confirm eligibility. If the subject meets the study selection criteria, according to the randomization protocol, an IRT will be used to assign a randomization number to the subject, which will be used to code the treatment group allocation for the subject. If the subject does not meet the research selection/qualification criteria, the research center staff must promptly register in the IRT system and determine the subject as a screening failure. The enrolled subjects were identified by the subject identification code assigned during the screening visit, which remained unchanged throughout the entire study period.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：

开放标签

Blinding：

Open-label study

是否共享原始数据：

IPD sharing

否No

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

无

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

N/A

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

无

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

N/A

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2026-01-16 09:37:05