注册号：
Registration number：
ChiCTR2600121048 最近更新日期：
Date of Last Refreshed on：
2026-03-24 17:35:33 注册时间：
Date of Registration：
2026-03-24 00:00:00 注册号状态：
预注册Registration Status：
Prospective registration注册题目：
注射用HS-20093联合阿得贝利单抗对比多西他赛在驱动基因阴性的晚期或转移性非鳞状非小细胞肺癌的有效性和安全性Public title：
A Multicenter, Randomized, Open-Label, Controlled Phase III Clinical Study Evaluating the Efficacy and Safety of HS-20093 Injection Combined with Adebrelimab versus Docetaxel in Previously Treated Patients With Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer without Actionable Genomic Alterations注册题目简写：English Acronym：
HS-20093-309研究课题的正式科学名称：
一项评估注射用HS-20093联合阿得贝利单抗对比多西他赛用于既往接受过以含铂化疗为基础的标准治疗后进展或复发的驱动基因阴性的晚期或转移性非鳞状非小细胞肺癌的有效性和安全性的多中心、随机、开放、对照、III期临床研究Scientific title：
A Multicenter, Randomized, Open-Label, Controlled Phase III Clinical Study Evaluating the Efficacy and Safety of HS-20093 Injection Combined with Adebrelimab versus Docetaxel in Previously Treated Patients With Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer without Actionable Genomic Alterations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：
赵艳辉
研究负责人：
任胜祥 Applicant：
Yanhui zhao
Study leader：
Ren shengxiang 申请注册联系人电话：
Applicant telephone：
+86 18652106586
研究负责人电话：
Study leader's telephone：
+86 21 65115006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：
zhaoyh8@hspharm.com
研究负责人电子邮件：
Study leader's E-mail：
harry_ren@126.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：
上海市浦东新区祥科路287号启慧大厦11楼
研究负责人通讯地址：
上海市杨浦区政民路507号Applicant address：
11th Floor, Qihui Building, No. 287, Xiangke Road, Pudong New Area, Shanghai
Study leader's address：
No. 507 Zhengmin Road, Yangpu 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：
上海翰森生物医药科技有限公司Applicant's institution：
Shanghai Hansoh Biomedical R&D Inc.研究负责人所在单位：
上海市肺科医院Affiliation of the Leader：
Shanghai Pulmonary 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：
25363ZL
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：
上海市肺科医院临床试验伦理审查委员会Name of the ethic committee：
Shanghai Pulmonary Hospital Clinical Trial Ethics Review Committee伦理委员会批准日期：
Date of approved by ethic committee：
2025-10-30 00:00:00伦理委员会联系人：
桂涛Contact Name of the ethic committee：
Gui Tao伦理委员会联系地址：
上海市杨浦区政民路507号Contact Address of the ethic committee：
No. 507 Zhengmin Road, Yangpu District, Shanghai伦理委员会联系人电话：
Contact phone of the ethic committee：
+86 21 65115006
伦理委员会联系人邮箱：
Contact email of the ethic committee：
fkyygcp@163.com研究实施负责（组长）单位：
上海市肺科医院Primary sponsor：
Shanghai Pulmonary Hospital研究实施负责（组长）单位地址：
上海市杨浦区政民路507号Primary sponsor's address：
No. 507 Zhengmin Road, Yangpu 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)：
上海市肺科医院
具体地址：
上海市杨浦区政民路507号
Institution
hospital：
Shanghai Pulmonary Hospital
Address：
No. 507 Zhengmin Road, Yangpu District, Shanghai经费或物资来源：
上海翰森生物医药科技有限公司Source(s) of funding：
Shanghai Hansoh Biomedical R&D Inc.研究疾病：
驱动基因阴性的晚期或转移性非鳞状非小细胞肺癌 Target disease：
Advanced or metastatic non-squamous non-small cell lung cancer with negative driver genes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：
III期临床试验 Study phase：
3研究设计：
随机平行对照 Study design：
Parallel 研究目的：
评价HS-20093 联合阿得贝利单抗对比多西他赛在接受过以含铂化疗为基础的标准治疗后进展或复发的驱动基因阴性的晚期或转移性非鳞状非小细胞肺癌（nsq-NSCLC）患者中的无进展生存期（PFS）（盲态独立中心阅片评估）和总生存期（OS） Objectives of Study：
To evaluate the progression-free survival (PFS) (assessed by blinded independent central review) and overall survival (OS) of HS-20093 in combination with adibelimab versus docetaxel in patients with advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) with negative driver genes who have progressed or relapsed after standard treatment based on platinum-containing chemotherapy.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. 在签署知情同意书（ICF）时年龄≥18 周岁，性别不限。
2. 自愿参加本次临床试验，理解研究程序且能够书面签署ICF，并承诺遵守本临床试验方案规定的所有要求。
3. 经组织学或细胞学确诊的晚期或转移性nsq-NSCLC（ⅢB/ⅢC/Ⅳ期，肿瘤分期依据AJCC第9版 肿瘤分期）。既往接受过以含铂化疗为基础的晚期一线标准系统性治疗后进展或复发，经研究者评估认为适宜参加本研究； ￚ 既往针对局部晚期疾病接受以根治为目的的治疗（包括或者新辅助/辅助治疗），在末次化疗或末次放疗6个月内出现疾病复发/进展可视为晚期一线。如果患者对含铂化疗不耐受，需要研究者评估并提供依据则允许入组。展或复发，经研究者评估认为适宜参加本研究；
4. 提供合格的基因检测报告证明未携带以下基因突变，包括：EGFR敏感突变、ALK融合突变、ROS1融合突变，如基因检测报告不可及或不合格，需提供足量肿瘤组织样本进行基因检测（具体见入选标准第6条）；同时根据现有资料，无其他驱动基因突变的证据。
5. 根据RECIST v1.1，参与者至少有一个靶病灶。曾经接受过放疗且在放疗后被证实进展的可测量病灶可作为靶病灶。
6. 优先提供新鲜肿瘤组织样本（样本类型为福尔马林固定、石蜡包埋[FFPE]的肿瘤组织块或FFPE 切片），样本需足够中心实验室进行PD-L1表达的检测和肿瘤基因检测（如基因检测报告不可及或不合格）及后续生物标志物分析（如B7-H3，样本足够的情况下）；如新鲜样本不可及，可接受2年内的FFPE肿瘤组织块新制备的FFPE切片。如肿瘤组织样本超过2年，与申办方协商一致则允许入组。
7. 东部肿瘤协作组体力评分（ECOG PS）评分为0～1分。
8. 最小预期生存大于12周。
9. 器官功能良好，研究给药前7天内满足以下实验室限值：
a) 中性粒细胞计数≥ 1.5×10^9/L（过去2周内无G-CSF纠正/支持治疗）；
b) 血小板计数≥ 100×10^9/L（过去1周内未接受过输血纠正/支持治疗）；
c) 血红蛋白≥ 90 g/L（血红蛋白需满足过去2周内未使用促红细胞生成素且未接受红细胞输注）；
d) 丙氨酸氨基转移酶（ALT）和/或天门冬氨酸氨基转移酶（AST）≤ 2.5×正常值上限（ULN）；如存在肝脏转移，则ALT和/或AST≤5.0×ULN（实验室检查抽血前7天内无纠正治疗）；
e) 总胆红素≤1.5×正常值上限（ULN）；若有明确的Gilbert综合症（非结合型高胆红素血症）或肝转移，总胆红素≤3.0×ULN；根据多西他赛说明书，需排除：总胆红素＞ULN和/或AST和/或ALT＞3.5×ULN，合并碱性磷酸酶（ALP）＞6×ULN（实验室检查抽血前7天内无纠正治疗）；
f) 肌酐≤1.5×ULN或肌酐清除率≥ 50 mL/ min（通过附录12.4的Cockcroft - Gault公式计算）；
g) 血清白蛋白（ALB）≥28 g/L；
h) 国际标准化比值（INR）或凝血酶原时间≤1.5×ULN，且活化部分凝血活酶时间（APTT） ≤1.5×ULN；若参与者正在接受抗凝治疗，则允许超过此限值，但需要稳定的抗凝治疗，且凝血酶原时间或APTT在抗凝药物的治疗目标范围内。
10. 不存在下列活动性病毒感染性疾病：
ￚ 乙肝（定义为筛选期病毒表面抗原[HBsAg]和/或核心抗体[HBcAb]检测结果呈阳性，同时检测到乙型肝炎病毒（HBV）-DNA 检测值≥2×103 IU/mL。若经规律抗病毒治疗再次复测降至 2×103 IU/mL 以下可入组） ￚ 丙肝（定义为筛选期丙肝病毒抗体[HCV-Ab]检测结果阳性，且 HCV-RNA 阳性）
ￚ 人类免疫缺陷病毒（HIV）感染（定义为抗 HIV 抗体阳性）
ￚ 结核（1 年内有活动性结核感染的证据）
ￚ 梅毒（梅毒螺旋体特异性抗体与非特异性抗体均阳性）；
11. 女性参与者在首次给药前7天内，血妊娠试验结果为阴性，或者满足下列标准之一证明没有妊娠风险：
a) 绝经后（具体定义见附录12.7）；
b) 未经初潮的女性；
c) 绝经前女性但具备以下条件之一：
- 有记录的全子宫切除术 - 有记录的双侧输卵管切除术或双侧输卵管结扎术
- 有记录的双侧卵巢切除术
d) 对于因其他医学原因导致永久不育的女性，由研究者判断该女性是否符合参与试验的标准。
12. 具有生育能力的女性参与者从签署知情同意起到末次给药后8个月内愿意采取合适的避孕措施（参考附录12.10）且不应该捐卵、哺乳。未来有生育意愿的女性参与者同意在研究治疗开始前进行卵子（卵母细胞）冷冻保存；男性参与者从签署知情同意起到末次给药后6个月内愿意使用屏障避孕且不应该捐精。未来有生育需求的男性参与者同意在研究治疗开始前冷冻精子样本。Inclusion criteria
1. When signing the ICF, the age should be 18 years or above, and there is no restriction on gender.
2. Voluntarily participate in this clinical trial, understand the research procedures, and be able to sign the ICF in person. Also, commit to complying with all the requirements stipulated in this clinical trial protocol.
3. Advanced or metastatic non-squamous non-small cell lung cancer (stage IIIB/III C/IV, tumor staging according to the 9th edition of the AJCC staging system). Previously received advanced first-line standard systemic treatment based on platinum-containing chemotherapy and subsequently progressed or relapsed; as assessed by the investigators, they are eligible to participate in this study.
4. Provide a qualified genetic test report certifying that no the following gene mutations are carried, including: EGFR sensitive mutations, ALK fusion mutations, and ROS1 fusion mutations. If the genetic test report is unavailable or (unqualified), a sufficient amount of tumor tissue samples must be provided for genetic testing (please refer to the 6th item of the inclusion criteria); at the same time, based on the existing data, there is no evidence of other driver gene mutations.
5. According to RECIST v1.1, each participant must have at least one target lesion. Measurable lesions that have progressed after radiotherapy and have been confirmed can be regarded as target lesions.
6. Prioritize the provision of fresh tumor tissue samples (sample type: formalin-fixed, paraffin-embedded [FFPE] tumor tissue blocks or FFPE sections). The samples must be sufficient for the central laboratory to conduct PD-L1 expression testing and tumor gene testing (such as if the genetic test report is unavailable or unqualified), as well as subsequent biomarker analysis (such as B7-H3, provided the sample is sufficient); if fresh samples are not available, prepared FFPE sections from newly prepared FFPE tumor tissue blocks within 2 years are acceptable. If the tumor tissue samples are older than 2 years, they can be included in the study upon agreement with the sponsor.
7. The Eastern Cooperative Oncology Group Performance Status (ECOG PS) score is 0 to 1.
8. The minimum expected survival period is more than 12 weeks.
9. The organ functions are normal. Within 7 days before the study administration, the following laboratory limits must be met:
a) Neutrophil count >= 1.5×10^9/L (without G-CSF correction/support treatment in the past 2 weeks);
b) Platelet count >= 100×10^9/L (without blood transfusion correction/support treatment in the past 1 week);
c) Hemoglobin >= 90 g/L (hemoglobin must meet the condition of no use of erythropoietin and no red blood cell transfusion in the past 2 weeks);
d) Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) <= 2.5× upper limit of normal (ULN); if there is liver metastasis, ALT and/or AST <= 5.0×ULN (without correction treatment 7 days before laboratory test);
e) Total bilirubin <= 1.5×ULN; if there is clear Gilbert syndrome (non-conjugated hyperbilirubinemia) or liver metastasis, total bilirubin <= 3.0×ULN; according to the docetaxel instructions, it is necessary to exclude: total bilirubin > ULN and/or AST and/or ALT > 3.5×ULN, combined with alkaline phosphatase (ALP) > 6×ULN (without correction treatment 7 days before laboratory test);
f) Creatinine <= 1.5×ULN or creatinine clearance rate >= 50 mL/min (calculated by Cockcroft-Gault formula in Appendix 12.4);
g) Serum albumin (ALB) >= 28 g/L;
h) International normalized ratio (INR) or prothrombin time <= 1.5×ULN, and activated partial thromboplastin time (APTT) <= 1.5×ULN; if the participant is receiving anticoagulation treatment, it is allowed to exceed this limit, but stable anticoagulation treatment is required, and prothrombin time or APTT is within the treatment target range of the anticoagulant drug.
10. The following active viral infectious diseases are excluded:
ㅡ Hepatitis B (defined as a positive result for the screening test of hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb], along with the detection of hepatitis B virus (HBV) DNA with a value of >= 2×10^3 IU/mL. If the value drops below 2×10^3 IU/mL after regular antiviral treatment, it can be included in the study)
ㅡ Hepatitis C (defined as a positive result for hepatitis C virus antibody [HCV-Ab] in the screening period, and positive HCV-RNA)
ㅡ Human Immunodeficiency Virus (HIV) infection (defined as positive anti-HIV antibody)
ㅡ Tuberculosis (with evidence of active tuberculosis infection within 1 year)
ㅡ Syphilis (positive results for both specific and non-specific antibodies of Treponema pallidum);
11. For female participants, the blood pregnancy test result was negative within 7 days before the first administration, or they met one of the following criteria to prove no pregnancy risk:
a) Postmenopausal (the specific definition is provided in Appendix 12.7);
b) Women who have never experienced menarche;
c) Pre-menopausal women but with one of the following conditions:
- Recorded total hysterectomy
- Recorded bilateral oophorectomy or bilateral tubal ligation
- Recorded bilateral oophorectomy
d) For women who are permanently infertile due to other medical reasons, the researcher will determine whether the woman meets the criteria for participating in the trial.
12. Female participants with reproductive capacity are willing to take appropriate contraceptive measures from the time of signing the informed consent until 8 months after the last administration (refer to Appendix 12.10), and should not donate eggs or breastfeed. Future female participants with the intention to have children agree to freeze their eggs (oocytes) before the start of the study treatment; male participants from the time of signing the informed consent until 6 months after the last administration are willing to use barrier contraception and should not donate sperm. Future male participants with the need for reproduction agree to freeze their sperm samples before the start of the study treatment.排除标准：
1. 既往病理诊断为混合型非小细胞肺癌（例如混合小细胞肺癌和非小细胞肺癌，混合鳞癌和腺癌）或任何转化型非小细胞肺癌（小细胞肺癌转化为非小细胞肺癌）。
2. 接受过或正在进行以下治疗：
a) 既往使用过或正在使用以B7-H3为靶点的治疗，例如：MGC018、DS-7300a、ABBV-155、 BAT8009、Enoblituzumab和Omburtamab等；
b) 既往使用过或正在使用拓扑异构酶I抑制物类药物的治疗，包括有效荷载为拓扑异构酶I抑制物的抗体偶联药物等，例如：拓扑替康、伊立替康、德曲妥珠单抗、戈沙妥珠单抗、Dato-Dxd（DS-1062）等；
c) 既往接受过多西他赛单药或与其他药物联合治疗；
d) 随机前2周内，接受过细胞毒性化疗药物、试验性药物、以抗肿瘤为适应症的中药治疗（药物名单详见附录12.1）或其他抗肿瘤药物（包括分子靶向治疗或生物治疗等）；
e) 随机前4周内接受大分子抗肿瘤药物治疗（包括免疫治疗，如单克隆抗体类药物和双特异性抗体类药物）；
f) 随机前2周内曾经接受局部放疗；随机前4周内，接受过超过30%的骨髓照射，或接受过大面积放疗；
g) 存在需要临床干预的胸腔积液/腹腔积液（不需要引流积液或引流积液后稳定1周以上的患者可以入组）；存在心包积液（研究者评估不需要临床干预的无症状的少量心包积液允许入组）。如引流时局部使用（如胸腔灌注）过抗肿瘤药物，同时需满足随机前洗脱至少5个药物半衰期或21天（以短者计）才可入组；
h) 随机前7天内，使用过细胞色素P450（CYP）3A4酶、CYP2D6、P-糖蛋白（P-gp）、乳腺癌耐药蛋白（BCRP）、有机阴离子转运多肽（OATP）1B1或OATP1B3的强抑制剂；或研究期间需要继续接受这些药物治疗（药物名单详见附录12.1）；
i) 正在接受已知可延长QT间期或可能导致尖端扭转性室性心动过速的药物治疗；或研究期间需要继续接受这些药物治疗（药物名单及洗脱时间详见附录12.1）。
3. 存在既往治疗引起的持续性不良反应，且这些不良反应尚未恢复至1级或既往治疗前的基线状态，但脱发、听力损失、白癜风、通过替代治疗稳定的内分泌疾病以及2级神经病变除外；或者研究者在与申办者协商一致后认为这些不良反应对于当前临床研究中参与者对研究干预措施的耐受性没有临床相关性。
4. 未经治疗的脑转移；脑转移未控制（除非无症状、肿瘤病灶周围无明显水肿的影像学表现，且 在首次给药前至少2周不需要类固醇治疗）；存在脑膜转移或脑干转移；存在脊髓压迫（通过放射影像学检查发现，无论是否有症状）。
5. 其他原发恶性肿瘤病史，除外：已根治的实体瘤，在入选研究之前≥5 年无活动并且复发风险极 低，如经充分治疗且无疾病复发证据的非黑色素瘤皮肤癌或恶性雀斑样痣；经充分治疗且无疾病复发证据的原位癌，如宫颈原位癌；有明确治疗的非转移性前列腺癌。
6. 存在以下任何心脏检查异常情况：
a) 存在当前具有临床意义的重要的心律失常或ECG异常的证据（例如，完全性左束支传导阻滞、三度房室传导阻滞、二度房室传导阻滞、PR间期>250 ms）；
b) 存在导致QT间期延长或心律失常事件的风险因素，例如心力衰竭、难治性低钾血症、先天性长QT综合征、长QT综合征家族史，或正在使用任何可能延长QT间期的合并用药；
c) 静息状态下的ECG检查得出的经Fridericia校正的QT间期（QTcF）平均值>470 msec，Fridericia公式见附录12.3；
d) 左心室射血分数< 50%。
7. 有严重的、未得到控制的或处于活动期的心脑血管疾病，包括但不限于以下情况：
a) 随机前6个月内发生过心肌梗死；
b) 随机前6个月内出现不稳定型心绞痛，且未能通过标准治疗方案控制；
c) 随机前6个月内出现充血性心力衰竭（纽约心脏协会心功能分级II级或以上的充血性心力衰 竭[纽约心脏协会标准委员会，1994]）；
d) 随机前6个月内发生过脑血管意外（中风）或短暂性脑缺血发作；
e) 有临床意义（由研究者判断）的房性心律失常病史，且未能通过标准治疗方案控制；
f) 有临床意义（由研究者判断）的室性心律失常病史，或在筛选期间发生任何具有临床意义的室性心律失常。 控制；
8. 患有严重或控制不佳的高血压，包括但并不限于：有高血压危象、高血压脑病病史；因血压控 制不佳而在随机前2周内调整降压药物。血压控制不佳定义为：在筛选期间收缩压≥180 mmHg或舒张压≥110 mmHg。
9. 严重或控制不佳的糖尿病，包括但不限于：①随机前6个月内发生过糖尿病酮症酸中毒或高血糖高渗状态；或②研究者认为存在其他严重或控制不佳的糖尿病情况。
10. 随机前4周内有严重感染，包括但不限于使用静脉注射抗生素治疗≥2周的感染性并发症、菌血症、重症肺炎；随机前2周内正在接受治疗性静脉注射抗生素的活动性感染。接受或曾接受预防性抗生素治疗的参与者（例如，预防尿路感染）允许入组。
11. 随机前1个月内有临床显著的出血症状或显著的出血倾向。
12. 随机前3个月内发生过严重的动脉或静脉血栓栓塞事件（例如深静脉血栓、肺栓塞等），但植入式静脉输液港相关血栓、导管相关血栓或浅静脉血栓除外（这些不被视为“严重”的血栓栓塞事件）。
13. 已知或可疑有间质性肺炎、免疫性肺炎或放射性肺炎病史；筛选期患有或疑似存在间质性肺炎、免疫性肺炎或放射性肺炎；或随机前存在其他可能会干扰药物相关肺毒性的检测或处理的、严重影响呼吸功能的中重度肺部疾病，包括但不限于特发性肺组织纤维化、机化性肺炎/闭塞性细支气管炎、筛选期肺功能检测结果为中度或重度通气功能障碍。
14. 患有活动性或存在病史且有可能复发的自身免疫性疾病的参与者（如系统性红斑狼疮、类风湿 性关节炎、炎症性肠病、自身免疫性甲状腺疾病、多发性硬化、血管炎、肾小球炎等），或高风险（如接受过器官移植需要接受免疫抑制治疗）的患者。但允许患以下疾病的参与者入组： 1）采用固定剂量的胰岛素后病情稳定的I 型糖尿病患者；2）只需接受激素替代治疗的自身免疫性甲状腺功能减退症；3）无需进行全身治疗的皮肤疾病（如湿疹、占体表10%以下的皮疹、无眼科症状的银屑病等）。需要支气管扩张剂进行医学干预的哮喘者不能纳入。
15. 既往发生过严重或危及生命的免疫介导不良事件（包括免疫药物治疗期间导致永久停药的不良事件）。
16. 具有任意以下情况：①首次给药前2个月内体重指数（BMI）＜18.0 kg/m^2或首次给药前2个月内 体重下降≥10%。②严重营养不良，患者当前正在接受静脉高营养治疗，或需住院接受持续静脉 输液治疗。若患者在随机前营养状况已得到有效控制且稳定超过28天可以入组。
17. 现患肝性脑病、肝肾综合征或≥Child-Pugh B级肝硬化。
18. 存在任何活动性肾脏疾病（例如感染、需要透析，或任何其他可能影响参与者安全的肾脏疾病）。注意：允许通过支架成功管理的肾梗阻。
19. 在随机前30天内已接受连续糖皮质激素治疗超过30天、或需要长期（≥30天）使用糖皮质激素治疗者（皮肤外用激素类药品的患者以及使用低剂量皮质类固醇作为肾上腺皮质功能减退替代治疗的患者除外），或患有其他获得性、先天性免疫缺陷疾病，或有移植史（角膜移植除外）。允许按生理替代剂量使用全身性糖皮质激素（≤10 mg/d泼尼松或其等效药物）。
20. 在首次给药前4周内接受过任何重大手术（开颅、开胸或开腹手术）。外科大手术定义参照 《医疗技术临床应用管理办法》中规定的3级和4级手术。
21. 既往有严重过敏史者（例如过敏性休克），或曾发生过严重的输液反应，或对重组人源或鼠源 蛋白类物质过敏。已知对研究药物（HS-20093、阿得贝利单抗、多西他赛或其他含聚山梨酯-80制剂）的任何成分或辅料存在过敏反应这些情况禁止其参与本研究。
22. 在随机前30天内接受过任何活疫苗。通过适当监管机制（例如紧急使用授权、有条件市场授权或许可证申请）授权的COVID-19疫苗接种不被排除。注意：mRNA和基于腺病毒的COVID-19疫苗被视为非活疫苗。
23. 目前正在入组或参与任何涉及研究性干预措施或其他类型干预性医学研究的其他临床研究。允许参与不涉及研究用药品给药的研究随访部分、非干预性注册研究或流行病学研究。
24. 存在任何严重和/或不稳定的医学或精神疾病或其他状况（包括实验室检查异常），可能会干扰 知情同意的获取、对研究程序的依从性，影响对结果的解释，或可能使参与者接受研究药物处 于高安全性风险。Exclusion criteria：
1. The previous pathological diagnosis was for mixed-type non-small cell lung cancer (such as mixed small cell lung cancer and non-small cell lung cancer, mixed squamous cell carcinoma and adenocarcinoma) or any transformed type non-small cell lung cancer (small cell lung cancer transformed into non-small cell lung cancer);
2. Have received or are currently receiving the following treatments:
a) Have used or are using treatments targeting B7-H3, such as MGC018, DS-7300a, ABBV-155, BAT8009, Enoblituzumab, and Omburtamab, etc.;
b) Have used or are using topoisomerase I inhibitor drugs for treatment, including antibody-drug conjugates with topoisomerase I inhibitors as the payload, etc., such as topotecan, irinotecan, deruxtegravir, goserelin, Dato-Dxd (DS-1062), etc.;
c) Have received docetaxel monotherapy or combination therapy with other drugs;
d) Within the 2 weeks prior to randomization, have received cytotoxic chemotherapy drugs, experimental drugs, traditional Chinese medicine for anti-tumor indications (drug list is detailed in Appendix 12.1), or other anti-tumor drugs (including molecular targeted therapy or biological therapy, etc.);
e) Within the 4 weeks prior to randomization, have received large molecule anti-tumor drug treatment (including immunotherapy, such as monoclonal antibody drugs and bispecific antibody drugs);
f) Within the 2 weeks prior to randomization, have received local radiotherapy; within the 4 weeks prior to randomization, have received more than 30% bone marrow irradiation, or have received extensive radiotherapy;
g) Have existing pleural effusion or peritoneal effusion that require clinical intervention (patients who do not need to drain the effusion or whose effusion stabilizes for more than 1 week after drainage can be enrolled); have pericardial effusion (patients with asymptomatic small amounts of pericardial effusion as evaluated by the investigator are allowed to be enrolled). If local anti-tumor drugs were used during drainage (such as intrathoracic perfusion), it is necessary to meet the requirement of at least 5 drug half-lives or 21 days (whichever is shorter) before randomization for enrollment;
h) Within the 7 days prior to randomization, have used strong inhibitors of cytochrome P450 (CYP) 3A4, CYP2D6, P-gp, breast cancer resistance protein (BCRP), organic anion transporter polypeptide (OATP) 1B1 or OATP1B3; or have needed to continue receiving these drugs during the study (drug list is detailed in Appendix 12.1);
i) Are currently receiving drugs known to prolong the QT interval or may cause torsades de pointes ventricular tachycardia; or need to continue receiving these drugs during the study (drug list and washout time are detailed in Appendix 12.1).
3. There are persistent adverse reactions caused by previous treatments, and these adverse reactions have not yet returned to grade 1 or the baseline state before the previous treatment, except for hair loss, hearing loss, vitiligo, stable endocrine diseases through alternative treatment, and grade 2 neuropathy. Or, after consultation with the sponsor, the researchers determined that these adverse reactions were not clinically relevant to the tolerance of the study intervention measures by the participants in the current clinical trial.
4. Untreated brain metastases; Uncontrolled brain metastases (unless there are no symptoms and no obvious edema around the tumor lesion on imaging, and no steroid treatment is required at least 2 weeks before the first administration); Presence of meningeal metastases or brainstem metastases; Presence of spinal cord compression (detected by radiological imaging, regardless of whether there are symptoms).
5. History of other primary malignant tumors, excluding: cured solid tumors, those that have been inactive for >= 5 years before enrollment in the study and have an extremely low risk of recurrence, such as non-melanoma skin cancer or malignant lentigo-like nevus that has been adequately treated and shows no evidence of disease recurrence; in situ cancer that has been adequately treated and shows no evidence of disease recurrence, such as cervical in situ cancer; non-metastatic prostate cancer that has been clearly treated.
6. Any of the following cardiac examination abnormalities exist:
a) There is evidence of a clinically significant arrhythmia or ECG abnormality at present (for example, complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, PR interval > 250 ms);
b) There are risk factors that cause QT interval prolongation or arrhythmia events, such as heart failure, refractory hypokalemia, congenital long QT syndrome, long QT syndrome family history, or the use of any concomitant medication that may prolong the QT interval;
c) The average QTcF value (corrected by Fridericia formula) obtained from the ECG examination at rest is > 470 msec, as shown in Appendix 12.3;
d) The left ventricular ejection fraction is < 50%.
7. There are severe, uncontrolled or active cardiovascular and cerebrovascular diseases, including but not limited to the following conditions:
a) A myocardial infarction occurred within the previous 6 months;
b) Unstable angina pectoris occurred within the previous 6 months and could not be controlled by standard treatment protocols;
c) Congestive heart failure (NYHA cardiac function grade II or above [NYHA Standards Committee, 1994]) occurred within the previous 6 months;
d) A cerebrovascular accident (stroke) or transient ischemic attack occurred within the previous 6 months;
e) A history of clinically significant atrial arrhythmia (judged by the researchers) that could not be controlled by standard treatment protocols;
f) A history of clinically significant ventricular arrhythmia, or any clinically significant ventricular arrhythmia occurred during the screening period.
8. Have severe or poorly controlled hypertension, including but not limited to: having a history of hypertensive crisis or hypertensive encephalopathy; adjusting antihypertensive medications within the first 2 weeks prior to randomization due to poor blood pressure control. Poor blood pressure control is defined as: systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg during the screening period.
9. Severe or poorly controlled diabetes, including but not limited to: a. Having experienced diabetic ketoacidosis or hyperglycemic hyperosmolar state within the previous 6 months; or b. Other severe or poorly controlled diabetes conditions as determined by the investigator.
10. Participants with severe infections within the previous 4 weeks, including but not limited to infectious complications treated with intravenous antibiotics for ≥ 2 weeks, bacteremia, severe pneumonia; active infections being treated with therapeutic intravenous antibiotics within the previous 2 weeks. Participants who have received or have received prophylactic antibiotic treatment (e.g., for preventing urinary tract infections) are allowed to be enrolled.
11. Had clinical symptoms of bleeding or significant bleeding tendency within the previous 1 month.
12. If there has been a severe arterial or venous thromboembolic event within the previous 3 months (such as deep vein thrombosis, pulmonary embolism, etc.), but including implantable venous infusion ports-related thrombosis, catheter-related thrombosis or superficial vein thrombosis (these are not regarded as "serious" thromboembolic events).
13. Known or suspected history of interstitial pneumonia, immune-related pneumonia or radiation-induced pneumonia; having or suspected to have interstitial pneumonia, immune-related pneumonia or radiation-induced pneumonia during the screening period; or having other severe and moderately debilitating pulmonary diseases that may interfere with the detection or management of drug-related pulmonary toxicity, or that significantly affect respiratory function, including but not limited to idiopathic pulmonary fibrosis, organizing pneumonia/obstructive bronchiolitis, and moderate or severe ventilation dysfunction as indicated by the pulmonary function test results during the screening period.
14. Participants with active or history of autoimmune diseases that may recur (such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or those at high risk (such as those who have undergone organ transplantation and need immunosuppressive treatment). However, participants with the following diseases are allowed to be enrolled:
1) Type 1 diabetic patients with stable condition after using a fixed dose of insulin;
2) Autoimmune hypothyroidism that only requires hormone replacement therapy;
3) Skin diseases that do not require systemic treatment (such as eczema, rashes covering less than 10% of the body surface, psoriasis without ocular symptoms, etc.). Patients with asthma who require medical intervention with bronchodilators cannot be included.
15. There have been previous serious or life-threatening immune-mediated adverse events (including adverse events that led to permanent discontinuation of immunotherapy during treatment).
16. Any of the following conditions must be met: a. Body Mass Index (BMI) was less than 18.0 kg/m^2 within 2 months prior to the first administration of the drug, or there was a weight loss of >=10% within 2 months prior to the first administration. b. Severe malnutrition. The patient is currently receiving intravenous high-nutrition therapy, or requires hospitalization for continuous intravenous infusion therapy. If the patient's nutritional status has been effectively controlled and stable for more than 28 days before randomization, they can be enrolled.
17. Presently suffering from hepatic encephalopathy, hepatorenal syndrome, or having liver cirrhosis at the >=Child-Pugh B grade.
18. There must be no active kidney diseases (such as infections, the need for dialysis, or any other kidney diseases that may affect the safety of the participants). Note: Renal obstruction that can be successfully managed through a stent is permitted.
19. Those who have received continuous glucocorticoid treatment for more than 30 days within the previous 30 days, or those who need long-term (>= 30 days) use of glucocorticoid treatment (excluding patients using topical hormone drugs or those using low-dose corticosteroids as replacement therapy for adrenal cortical insufficiency), or those with other acquired or congenital immune deficiency diseases, or those with a history of transplantation (except corneal transplantation), are allowed to use systemic glucocorticoids at the physiological replacement dose (<= 10 mg/d prednisone or its equivalent).
20. Within 4 weeks prior to the first administration, any major surgery (such as craniotomy, thoracotomy, or laparotomy) was performed. The definition of major surgical procedures refers to those classified as level 3 and level 4 surgeries as stipulated in the "Clinical Application Management Measures for Medical Technologies".
21. Those with a history of severe allergies (such as anaphylactic shock), or who have experienced severe infusion reactions, or who are allergic to recombinant human or murine protein substances. If there is a known allergic reaction to any component or excipient of the study drug (HS-20093, Adabepilimab, Docetaxel, or other formulations containing polysorbate-80), such individuals are prohibited from participating in this study.
22. Those who received any live vaccine within the previous 30 days prior to the randomization. Vaccination with COVID-19 vaccines authorized through appropriate regulatory mechanisms (such as emergency use authorization, conditional market authorization, or license application) are not excluded. Note: mRNA and adenovirus-based COVID-19 vaccines are regarded as non-live vaccines.
23. Currently, I am either being enrolled in or participating in any other clinical studies that involve investigational interventions or other types of interventional medical research. Participation is allowed in the follow-up sections of studies that do not involve the administration of investigational drugs, non-interventional registry studies, or epidemiological studies.
24. There are any serious and/or unstable medical or mental disorders or other conditions (including abnormal laboratory test results), which may interfere with the acquisition of informed consent, compliance with the research procedures, affect the interpretation of the results, or may expose the participants to high safety risks when receiving the research drugs.研究实施时间：
Study execute time：
从
From
2025-08-01 00:00:00至
To
2029-12-31 00:00:00
征募观察对象时间：
Recruiting time：
从
From
2026-03-25 00:00:00
至
To
2028-01-31 00:00:00干预措施：
Interventions：
组别：
试验组
样本量：
225
Group：
Test group
Sample size：
干预措施：
注射用HS-20093组联合阿得贝利单抗
干预措施代码：
Intervention：
Injection of HS-20093 group combined with Adalimumab
Intervention code：
组别：
对照组
样本量：
225
Group：
Control group
Sample size：
干预措施：
多西他赛注射液
干预措施代码：
Intervention：
Docetaxel Injection
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)：
上海市肺科医院
单位级别：
三级甲等
Institution
hospital：
Shanghai Pulmonary Hospital
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)：
四川省肿瘤医院
单位级别：
三级甲等
Institution
hospital：
Sichuan Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
福建省
市(区县)：
Country：
China
Province：
Fujian
City：
单位(医院)：
福建省肿瘤医院
单位级别：
三级甲等
Institution
hospital：
Fujian Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
山东省
市(区县)：
Country：
China
Province：
Shandong
City：
单位(医院)：
滨州医学院附属医院
单位级别：
三级甲等
Institution
hospital：
Binzhou Medical University Affiliated Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
河南省
市(区县)：
Country：
China
Province：
Henan
City：
单位(医院)：
河南省肿瘤医院
单位级别：
三级甲等
Institution
hospital：
Henan Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
湖南省
市(区县)：
Country：
China
Province：
Hunan
City：
单位(医院)：
湖南省肿瘤医院
单位级别：
三级甲等
Institution
hospital：
Hunan Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
福建省
市(区县)：
Country：
China
Province：
Fujian
City：
单位(医院)：
福建医科大学附属协和医院
单位级别：
三级甲等
Institution
hospital：
Fujian Medical University Union Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
河南省
市(区县)：
Country：
China
Province：
Henan
City：
单位(医院)：
郑州大学第一附属医院
单位级别：
三级甲等
Institution
hospital：
Zhengzhou University First Affiliated 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)：
北京大学肿瘤医院
单位级别：
三级甲等
Institution
hospital：
Peking University Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
山东省
市(区县)：
Country：
China
Province：
Shandong
City：
单位(医院)：
山东第一医科大学附属肿瘤医院（山东省肿瘤防治研究院、山东省肿瘤医院）
单位级别：
三级甲等
Institution
hospital：
Shandong Cancer Hospital
Level of the institution：
Tertiary A测量指标：
Outcomes：
指标中文名：
无进展生存期（PFS）
指标类型：
主要指标
Outcome：
Progression free survival, PFS
Type：
Primary indicator
测量时间点：
每6 周1 次（±7 天）至第48 周，48 周 之后每12 周1 次（±7 天）
测量方法：
CT/MRI影像
Measure time point of outcome：
Once every 6 weeks (+/-7 days) up to the 48th week, and then once every 12 weeks (+/-7 days)
Measure method：
CT/MRI images
指标中文名：
客观缓解率（ ORR ）
指标类型：
次要指标
Outcome：
Objective response rate, ORR
Type：
Secondary indicator
测量时间点：
每6 周1 次（±7 天）至第48 周，48 周 之后每12 周1 次（±7 天）
测量方法：
CT/MRI影像
Measure time point of outcome：
Once every 6 weeks (+/-7 days) up to the 48th week, and then once every 12 weeks (+/-7 days)
Measure method：
CT/MRI images
指标中文名：
AE发生率
指标类型：
次要指标
Outcome：
The incidence rate of AE
Type：
Secondary indicator
测量时间点：
测量方法：
血常规、血生化、尿常规、心电图等安全性检查
Measure time point of outcome：
Measure method：
Safety checks such as blood routine, blood biochemistry, urine routine, and electrocardiogram tests
指标中文名：
抗HS-20093 ADA抗体阳性患者比例
指标类型：
次要指标
Outcome：
The proportion of patients with positive anti-HS-20093 ADA antibodies
Type：
Secondary indicator
测量时间点：
C1D1、C2D1、C3D1、C4D1、C6D1、C8D1、C11D1及之后每3周期一次
测量方法：
PK药代动力学
Measure time point of outcome：
C1D1、C2D1、C3D1、C4D1、C6D1、C8D1、C11D1 and thereafter, once every three cycles
Measure method：
PK
指标中文名：
缓解持续时间（DoR）
指标类型：
次要指标
Outcome：
Duration of Relief, DoR
Type：
Secondary indicator
测量时间点：
每6 周1 次（±7 天）至第48 周，48 周 之后每12 周1 次（±7 天）
测量方法：
CT/MRI影像
Measure time point of outcome：
Once every 6 weeks (+/-7 days) up to the 48th week, and then once every 12 weeks (+/-7 days)
Measure method：
CT/MRI images
指标中文名：
疾病控制率（DCR）
指标类型：
次要指标
Outcome：
Disease Control Rate, DCR
Type：
Secondary indicator
测量时间点：
每6 周1 次（±7 天）至第48 周，48 周 之后每12 周1 次（±7 天）
测量方法：
CT/MRI影像
Measure time point of outcome：
Once every 6 weeks (+/-7 days) up to the 48th week, and then once every 12 weeks (+/-7 days)
Measure method：
CT/MRI images
指标中文名：
SAE严重程度
指标类型：
次要指标
Outcome：
SAE severity
Type：
Secondary indicator
测量时间点：
测量方法：
血常规、血生化、尿常规、心电图等安全性检查
Measure time point of outcome：
Measure method：
Safety checks such as blood routine, blood biochemistry, urine routine, and electrocardiogram tests
指标中文名：
总生存期（OS）
指标类型：
主要指标
Outcome：
Overall survival, OS
Type：
Primary indicator
测量时间点：
每6 周1 次（±7 天）至第48 周，48 周 之后每12 周1 次（±7 天）
测量方法：
CT/MRI影像
Measure time point of outcome：
Once every 6 weeks (+/-7 days) up to the 48th week, and then once every 12 weeks (+/-7 days)
Measure method：
CT/MRI images
指标中文名：
抗阿得贝利单抗抗体（ADA）的阳性患者比例
指标类型：
次要指标
Outcome：
The proportion of patients who are positive for the anti-Adalimumab antibody (ADA)
Type：
Secondary indicator
测量时间点：
C1D1、C2D1、C3D1、C4D1、C6D1、C8D1、C11D1及之后每3周期一次
测量方法：
PK药代动力学
Measure time point of outcome：
C1D1、C2D1、C3D1、C4D1、C6D1、C8D1、C11D1 and thereafter, once every three cycles
Measure method：
PK
指标中文名：
AE严重程度
指标类型：
次要指标
Outcome：
AE severity
Type：
Secondary indicator
测量时间点：
测量方法：
血常规、血生化、尿常规、心电图等安全性检查
Measure time point of outcome：
Measure method：
Safety checks such as blood routine, blood biochemistry, urine routine, and electrocardiogram tests
指标中文名：
SAE发生率
指标类型：
次要指标
Outcome：
The incidence rate of SAE
Type：
Secondary indicator
测量时间点：
测量方法：
血常规、血生化、尿常规、心电图等安全性检查
Measure time point of outcome：
Measure method：
Safety checks such as blood routine, blood biochemistry, urine routine, and electrocardiogram tests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：
肿瘤组织样本
组织：
Sample Name：
Tumor tissue sample
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）：
网络交互应答系统（IWRS）对参与者进行随机化入组Randomization Procedure (please state who
generates the
random number sequence and by what method)：
IWRS randomizes participants into groups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）：
NAThe way of sharing IPD”(include metadata and
protocol,
If use web-based public database, please provide
the
url)：
NA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：
NAData collection and Management (A
standard data collection and management system
include a CRF and an electronic data capture：
NA数据与安全监察委员会：
Data and Safety Monitoring Committee：
无/No注册人：
Name of Registration：
2026-03-24 17:35:10
