中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2600116103
最近更新日期： Date of Last Refreshed on：	2026-01-05 17:52:04
注册时间： Date of Registration：	2026-01-05 00:00:00
注册号状态：	补注册
Registration Status：	Retrospective registration
注册题目：	一项评估 KY-0301 单药在晚期实体瘤患者中的安全性、耐受性、药代动力学和初步疗效的首次人体、多中心、开放的 I/II 期临床研究
Public title：	A First-In-Human, Multicenter, Open-Label Phase I/II Investigational Study to Evaluate the Safety, Tolerability, Pharmacokinetics, And Preliminary Efficacy of KY-0301 as monotherapy or combined with other anticancer agents in Patients with advanced Solid Tumors
注册题目简写：
English Acronym：
研究课题的正式科学名称：	一项评估 KY-0301 单药在晚期实体瘤患者中的安全性、耐受性、药代动力学和初步疗效的首次人体、多中心、开放的 I/II 期临床研究
Scientific title：	A First-in-human, Multicenter, Open-label Phase I/II Investigational Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of KY-0301 as Monotherapy in Patients With Advanced Solid Tumors.
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：	李佳芮	研究负责人：	周彩存
Applicant：	Jiarui Li	Study leader：	Caicun Zhou
申请注册联系人电话： Applicant telephone：	+86 166 2172 4068	研究负责人电话： Study leader's telephone：	+86 21 3888 4518
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：	RA@novatim-zj.com	研究负责人电子邮件： Study leader's E-mail：	caicunzhoudr@tongji.edu.cn
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：	上海市浦东新区紫萍路908弄5号楼	研究负责人通讯地址：	上海市浦东新区云台路1800号
Applicant address：	Building 5, Lane 908, Ziping Road, Pudong New Area, 201318, Shanghai, China	Study leader's address：	No. 1800 Yuntai Road, Pudong New Area, Shanghai, China
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：	科弈(浙江)药业科技有限公司
Applicant's institution：	Novatim Immune Therapeutics (Zhejiang) Co., Ltd.
研究负责人所在单位：	上海市东方医院
Affiliation of the Leader：	Shanghai East 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：	[2025]临审第(024)号; [2025]临审第(024)号修正1	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：	上海市东方医院药物临床试验伦理委员会
Name of the ethic committee：	Shanghai East Hospital Ethic Committee of Clinical Trial Drug
伦理委员会批准日期： Date of approved by ethic committee：	2025-03-11 00:00:00
伦理委员会联系人：	鲍思蔚
Contact Name of the ethic committee：	Siwei Bao
伦理委员会联系地址：	上海市浦东新区云台路1800号
Contact Address of the ethic committee：	No. 1800 Yuntai Road, Pudong New Area, Shanghai,China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 21 3880 4518	伦理委员会联系人邮箱： Contact email of the ethic committee：

研究实施负责（组长）单位：

上海市东方医院

Primary sponsor：

Shanghai East Hospital

研究实施负责（组长）单位地址：

上海市浦东新区云台路1800号

Primary sponsor's address：

No. 1800 Yuntai Road, Pudong New Area, Shanghai,China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	浙江	市(区县)：	湖州
Country：	China	Province：	Zhejiang	City：	Huzhou
单位(医院)：	科弈（浙江）药业科技有限公司	具体地址：	浙江省湖州市安吉县递铺街道越都中路浙北生命健康小微园1号楼302室
Institution hospital：	Novatim Immune Therapeutics (Zhejiang) Co., Ltd.	Address：	Building 5, Lane 908, Ziping Road, Pudong New Area, 201318, Shanghai, China

经费或物资来源：

申办者

Source(s) of funding：

Sponsor

研究疾病：

实体瘤

Target disease：

Advanced Solid Tumor

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：

I期+II期

Study phase：

1-2

研究设计：

单臂

Study design：

Single arm

研究目的：

•评估KY-0301在不可手术切除的局部晚期或转移性实体瘤[包括但不限于表皮生长因子受体（EGFR）野生型或突变型非鳞状细胞非小细胞肺癌（nsq-NSCLC，EGFRwt或EGFRm）、鳞状非小细胞肺癌（sq- NSCLC）、结直肠癌（CRC）、晚期胃癌/食管胃交界处腺癌（GC/EGJA）、头颈鳞癌（HNSCC）等]患者中的安全性和耐受性； •在不可手术切除的局部晚期或转移性实体瘤（包括但不限于nsq-NSCLC, EGFRwt或EGFRm NSCLC、sq-NSCLC、CRC、GC/EGJA、HNSCC等）患者中确定KY-0301的最大耐受剂量（MTD）和推荐扩展剂量[RED（s）]；确定KY-0301在不可手术切除的局部晚期或转移性实体瘤（nsq-NSCLC，EGFRwt或EGFRm NSCLC、sq-NSCLC、CRC、GC/EGJA、HNSCC等）患者中的Ⅱ期推荐剂量（RP2D）。

Objectives of Study：

To evaluate the safety and tolerability of KY-0301 in patients with unresectable locally advanced or metastatic solid tumors [including but not limited to epidermal growth factor receptor (EGFR) wild-type or mutant non-squamous non-small cell lung cancer (nsq-NSCLC, EGFRwt or EGFRm), squamous non-small cell lung cancer (sq-NSCLC), colorectal cancer (CRC), advanced gastric cancer/adenocarcinoma of the esophagogastric junction (GC/EGJA), and head and neck squamous cell carcinoma (HNSCC)]. To determine the maximum tolerated dose (MTD) and recommended expansion dose(s) [RED(s)] of KY-0301 in patients with unresectable locally advanced or metastatic solid tumors [including but not limited to nsq-NSCLC, EGFRwt or EGFRm NSCLC, sq-NSCLC, CRC, GC/EGJA, and HNSCC]. To establish the recommended Phase II dose (RP2D) of KY-0301 in patients with unresectable locally advanced or metastatic solid tumors [including but not limited to nsq-NSCLC, EGFRwt or EGFRm NSCLC, sq-NSCLC, CRC, GC/EGJA, and HNSCC].

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

患者必须满足以下所有入选标准才可入组本研究：
1.在试验开始前已知试验信息，并自愿签署知情同意书（ICF）。
2.年龄≥18岁，男女不限。
3.愿意遵循而且有能力完成所有试验程序。
4.女性体重＞45kg，男性体重＞50kg，且BMI≥18kg/m^2。
5.瘤种类型
第一部分：KY-0301单药I期剂量递增阶段&剂量扩展阶段
•经组织学或细胞学证实的局部晚期或转移性实体瘤[包括但不限于EGFR野生型或突变型非鳞状细胞非小细胞肺癌（nsq-NSCLC，EGFRwt或EGFRm）、鳞状非小细胞肺癌（sq-NSCLC）、结直肠癌（CRC）、晚期胃癌/食管胃交界处腺癌（GC/EGJA）、头颈鳞癌（HNSCC）等]患者；
•现有标准治疗方案失败，对标准治疗不耐受或无标准治疗方案，或现阶段无法接受标准治疗的患者（例如：患者存在标准治疗禁忌，或经研究者评估患者一般状况预期无法耐受标准治疗等）；
第二部分：KY-0301单药Ⅱ期队列扩展阶段
•队列A
经组织学或细胞学确诊为局部晚期或转移性非鳞状非小细胞肺癌（NSCLC），不适合根治性手术或放疗；
具有肿瘤组织或血液样本有资质的实验室确认的携带一种或多种EGFR敏感突变的NSCLC患者，这些突变包括L858R、19Del；
先前接受过三代EGFR TKI一线治疗，且在治疗期间或之后有影像学证据显示进展或有病例记录显示疾病进展或不耐受；
针对仅接受过第一代或第二代 EGFR TKI一线治疗患者，需提供T790M突变阴性报告，无需经第三代EGFR TKI治疗；
至少接受过1线含铂双药标准全身化疗；
患者必须在既往末次抗肿瘤治疗至入组本研究期间有经放射影像学证实的疾病进展；
允许既往辅助或新辅助治疗（除奥希替尼外的化疗、放疗）。
•队列B 
经组织学或细胞学确诊为EGFR野生型的NSCLC；
有明确记录患者未发现可治疗的基因突变（如EGFR激活突变、ALK重排、ROS1重排、KRAS突变、BRAF突变、NTRK融合、MET14外显子跳跃突变、融合突变、ERBB2突变等）；
对于PD-L1表达阳性的患者，针对局部晚期或转移性疾病，既往接受过至少一线抗PD-(L)1免疫治疗及化疗；
患者必须在既往末次抗肿瘤治疗至入组本研究期间有经放射影像学证实的疾病进展。
•队列C 
经组织学或细胞学确诊为结直肠癌（CRC）；
对于高度微卫星不稳定（MSI-H）的患者，针对局部晚期或转移性疾病，既往接受过至少一线抗PD-(L)1免疫治疗及化疗；
针对复发/晚期转移性疾病，全身系统性治疗阶段不超过3线化疗；
患者必须在既往末次抗肿瘤治疗至入组本研究期间有经放射影像学证实的疾病进展。
6.美国东部肿瘤协作组体能状态评分（ECOG PS）（详见附录 1）为0或1。
7.器官功能必须符合以下标准：
•血红蛋白（Hb）≥8.5 g/dL（85 g/L）（首次给药前14天内未接受过输血、白蛋白或促红细胞生成素治疗）；
•中性粒细胞绝对数（ANC）≥1.5×10^9/L（首次给药前14天内未接受粒细胞集落刺激因子或粒细胞-巨噬细胞集落刺激因子治疗）；
•血小板计数（PLT）≥100×10^9/L（首次给药前14天内未接受血小板输注、血小板生成素或白细胞介素-11或海曲泊帕治疗）；
•没有肝脏病灶时（原发灶或转移灶），总胆红素≤1.5×ULN；有肝脏病灶时，总胆红素≤3×ULN；
•没有肝脏病灶时（原发灶或转移灶），丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）≤2.5×ULN；有肝脏病灶时，ALT和AST≤5×ULN；
•肌酐清除率≥60 mL/min（采用Cockcroft-Gault公式计算，详见附录 2）且血清肌酐≤1.5×ULN；
•活化部分凝血活酶时间（APTT）≤1.5×ULN和国际标准化比值（INR）≤1.5；接受抗凝治疗者要求INR维持在临床治疗范围内（＜4）；
•血清白蛋白≥30 g/L（3.0 g/dL）。
8.第一部分（Ⅰ期剂量递增阶段）的患者至少有一个影像学可评估的病灶。第一部分（Ⅰ期剂量扩展阶段），第二部分（Ⅱ期队列扩展阶段）的患者至少有一个可测量的颅外病灶（非放射疗野）。按照实体瘤的疗效评价标准（RECIST） v1.1（详见附录 3）进行评估。
9.预期生存期≥3个月。
10.有生育能力的女性患者，从筛选期开始到整个研究期间，以及末次接受研究药物后至少6个月内必须同意使用有效的避孕方式，并且不得捐献或取卵供自己使用。男性患者，从筛选期开始到整个研究期间，以及末次接受研究药物后至少6个月内，必须同意使用有效的避孕方式，不得冷冻或捐献精子（详见附录 4）；
11.患者可提供经福尔马林固定的石蜡包埋肿瘤组织切片，优先选择新鲜活检的肿瘤组织，如为存档肿瘤组织，要求距离签署本研究知情同意书最近一次的肿瘤组织，6个月内最佳，最长不超过2年。第一部分，对无法提供肿瘤样本或样本不足或样本超期的患者，经与申办者讨论后，也有可能入组。第二部分则必须提供肿瘤样本；对于样本不足的患者，经与申办者讨论后可根据具体情况入组。

Inclusion criteria

Patients must meet all of the following inclusion criteria to be eligible:
1. Know the trial information before the start of the study and voluntarily sign an informed consent form (ICF).
2. Aged >= 18 years, male or female.
3. Agree to follow and be capable of completing all study procedures.
4. Female weight > 45 kg, male weight > 50 kg, with a BMI >=18 kg/m^2.
5. Tumor Types
Part I: Phase I Dose Escalation & Dose Expansion Phases of KY-0301 as monotherapy
Patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors [including but not limited to EGFR wild-type or mutant non-squamous non-small cell lung cancer (nsq-NSCLC, EGFRm, EGFRwt), squamous non-small cell lung cancer (sq-NSCLC), colorectal cancer (CRC), advanced gastric cancer/esophagogastric junction adenocarcinoma (GC/EGJA), and head and neck squamous cell carcinoma (HNSCC)].
Patients who have failed existing standard treatment regimens, are intolerant to standard treatment, have no standard treatment regimen, or are currently not suitable for standard treatment;
Patients must have radiographically confirmed disease progression from the last antitumor treatment to the time of enrollment in this study.
Part II: Phase II Cohort Expansion Phase of KY-0301 as monotherapy
•	Cohort A
Histologically or cytologically confirmed locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) that is not suitable for curative surgery or radiotherapy.
Patients with NSCLC carrying one or more EGFR-sensitive mutations that include L858R, 19Del, as confirmed by a qualified laboratory with tumor tissue or blood samples.
Patients who have previously received first-line third-generation EGFR TKI therapy and have radiographic evidence of progression or documented disease progression or intolerance during or after treatment.
For patients who have only received first- or second-generation EGFR TKI as first-line therapy, a negative report for the T790M mutation must be provided, without the need for treatment with a third-generation EGFR TKI;
Patients must have received at least 1st line platinum-containing two-drug standard systemic chemotherapy;
Patients must have radiographically confirmed disease progression from the last prior anticancer therapy to the enrollment in this study;
Previous adjuvant or neoadjuvant therapy (excluding chemotherapy or radiotherapy involving Osimertinib) is allowed.
•	Cohort B 
Histologically or cytologically confirmed NSCLC with wild-type EGFR;
Clear documentation showing that no actionable genetic mutations have been identified (e.g., EGFR activating mutations, ALK rearrangement, ROS1 rearrangement, KRAS mutations, BRAF mutations, NTRK fusions, MET exon 14 skipping mutation, fusion mutations, and ERBB2 mutations).
For patients with positive PD-L1 expression, they have received at least first-line anti-PD - (L) 1 immunotherapy and chemotherapy for locally advanced or metastatic diseases;
Patients must have radiographically confirmed disease progression from the last antitumor treatment to the time of enrollment in this study.
•	Cohort C 
Histologically or cytologically confirmed CRC.
For patients with microsatellite instability-high (MSI-H) disease, at least one prior first-line anti-PD- (L) 1 immunotherapy and chemotherapy for locally advanced or metastatic disease;
For recurrent/advanced metastatic disease, no chemotherapy above the 3rd line is received in the systemic treatment phase;
Patients must have radiographically confirmed disease progression from the last antitumor treatment to the time of enrollment in this study.
Part III: Phase I Dose Escalation & Dose Expansion Phases of KY-0301 in Combination with Osimertinib
•	Histologically or cytologically confirmed diagnosis of locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC);
•	Patients with NSCLC carrying one or more EGFR-sensitive mutations, including L858R, 19Del, as confirmed by a qualified laboratory with tumor tissue or blood samples.
•	Patients must have radiographically confirmed disease progression from the last prior anticancer therapy to the first dosing of this study;
•	Requirements for the dose escalation phase
Previously received third-generation EGFR TKI as first-line therapy and had radiographic evidence of progression during or after treatment or documented disease progression or intolerance;
For patients who have only received first- or second-generation EGFR TKI as first-line therapy, a negative report for the T790M mutation must be provided without needing treatment with a third-generation EGFR TKI.
•	Requirements for dose expansion phase
Patients must not have received any prior systemic therapy.
Note: EGFR mutation-positive patients in Parts I, II, and III who have received one or two cycles of platinum-based chemotherapy prior to starting the third-generation EGFR TKi without progress and are awaiting EGFR status results will not be counted in "prior platinum therapy".
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) (see Appendix 1 for details) of 0 or 1.
7. Organ function must meet the following criteria:
•	Hemoglobin (Hb) >= 8.5 g/dL (85 g/L) (no blood transfusions, albumin, or erythropoietin treatment within 14 days prior to the first dose).
•	Absolute neutrophil count (ANC) >= 1.5 × 10^9/L (no granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor treatment within 14 days prior to the first dose);
•	Platelet count (PLT) >= 100 × 10^9/L (no platelet transfusion, thrombopoietin, interleukin-11, or herombopag treatment within 14 days prior to the first dose);
•	Total bilirubin <= 1.5 × ULN in the absence of liver lesions (primary or metastatic); total bilirubin <= 3 x ULN in the presence of liver lesions;
•	ALT and AST <= 2.5 × ULN in the absence of liver lesions (primary or metastatic); ALT and AST <= 5 × ULN in the presence of liver lesions;
•	Creatinine clearance >= 60 mL/min (calculated using the Cockcroft-Gault formula, see Appendix 2 for details) and serum creatinine <= 1.5 × ULN;
•	Activated partial thromboplastin time (APTT) <= 1.5 × ULN and international normalized ratio (INR) <= 1.5.
•	Serum albumin >= 30 g/L (3.0 g/dL).
8. Patients in Part I (Phase I dose escalation phase) must have at least one radiologically evaluable lesion. For patients in Part 1 (Phase I dose-expansion), Part 2 (Phase II cohort-expansion), and Part III, at least one measurable extracranial lesion (outside of the radiation field) is required. Assessments were performed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (see Appendix 3 for details).
9. Expected survival period >= 3 months.
10. Female patients of childbearing potential must agree to use effective contraception from the screening phase throughout the study period, and for at least 6 months after final receipt of study drug, and may not donate or remove eggs for their own use. Male patients must agree to use an effective form of contraception and not to freeze or donate sperm starting at Screening throughout the duration of the study and for at least 6 months after the last dose of the investigational drug (see Appendix 4 for details);
11. Patients must provide formalin-fixed paraffin-embedded (FFPE) tumor tissue slides. In Part I, patients who fail to provide a tumor sample or provide an insufficient or overdue sample may also be enrolled after discussion with the sponsor. In Parts II and III, tumor samples must be provided; patients with insufficient samples may be enrolled on a case-by-case after discussion with the sponsor.

排除标准：

符合以下任何一条标准的患者不可入组： 1.既往对单甲基澳瑞他汀E（MMAE）组成的ADC治疗不耐受史。 2.首次给药前既往抗肿瘤治疗的洗脱期不足，定义如下： • 任何细胞毒性化疗或小分子靶向治疗<3周或5个半衰期，以较短者为准（含5-氟尿嘧啶、亚叶酸钙和/或紫杉醇治疗方案者，需洗脱至少2周；亚硝基脲类或丝裂霉素 C需洗脱至少6周）； • 抗肿瘤内分泌治疗<3周； • 单抗或其他生物治疗<3周； • 酪氨酸激酶抑制剂治疗<1周； • 免疫靶向治疗<4周 • 具有抗肿瘤适应症的中药（详见附录 5）<2周； • 宽野放射治疗或对30%以上的骨髓进行放射治疗<4周，立体定向放疗<2周，全脑放疗<2周或立体定向脑部放疗<1周，姑息性放疗<2周。 3.首次给药前4周内接受过重大手术（不包括诊断性手术）或计划在研究期间进行重大手术者。在试验药物首次给药前2周内接受过针对治疗肿瘤为目的的介入或消融手术。 4.既往接受过异基因骨髓移植或既往接受过实体器官移植。 5.在试验药物首次给药前2周内接受过全身类固醇（>20 mg/天的泼尼松或等效药物）或其他免疫抑制治疗，除外以下情况： • 鼻内、吸入或局部类固醇注射（如关节内注射）； • 生理剂量的全身类固醇作为替代疗法（如针对肾上腺或垂体功能不全的生理性皮质类固醇替代疗法）； • 类固醇作为预防超敏反应或预防止吐等预防用药（如计算机断层扫描（CT）预防用药）。 6.在首次给药前4周内接种任何活疫苗，或计划在研究期间接种活疫苗。 7.软脑膜癌或癌性脑膜炎病史。 8.脑转移或脊髓压迫，除外以下情况： • 如果患者为无症状脑转移，且脑转移病灶较距离筛选期最近一次的颅脑CT/MRI无明显进展（例如新增多发脑转移和/或局部病灶明显增大），研究者评估治疗上也不需要立即进行局部或全身治疗（如甘露醇或皮质类固醇）者，允许入组； • 如果患者的脑转移灶经过治疗，转移灶病情稳定（首次给药前至少4周的脑部影像学检查显示病灶稳定，没有新发神经系统症状，而且在首次给药前2周内不需要立即进行局部或全身治疗）、且没有新发或原先脑转移灶增大的证据，则允许入组。 9.未控制或具有重大临床意义的心脑血管疾病，包括但不限于： • 首次给药前6个月内有症状性充血性心力衰竭[纽约心脏病协会（NYHA）功能分级为II至IV级，详见附录 6]或任何动脉血栓栓塞事件（如心肌梗死、不稳定型心绞痛、脑血管意外、短暂性脑缺血发作）病史或接受过经皮冠状动脉血管成形术或冠状动脉搭桥术； • 既往发生过肺栓塞或首次给药前3个月内发生的严重动静脉血栓形成事件，如深静脉血栓形成等； • 未控制的高血压，经过两种或两种以上药物联合治疗未控制的高血压，在降压治疗后收缩压（SBP）≥160 mmHg和/或舒张压（DBP）≥100 mmHg； • 研究者认为有可能增加QT间期延长风险的其他心律失常或临床状态，如完全性左束支传导阻滞、Ⅲ度房室传导阻滞、先天性长QT综合征、严重低钾血症、有长QT间期综合征家族史或不到40岁就不明原因猝死、尽管接受治疗但仍有症状或未受控制的房颤或无症状持续性室性心动过速等； • 在静息状态下，12导联心电图检查得出的按Fridericia公式（详见附录 7）校正的QT间期（QTcF）延长至>470 ms（无论性别）（注：若首次检查异常，48小时内复测2次，取3次平均值判断合格性）； • 超声心动图（ECHO）的左心室射血分数（LVEF）<50%。 10.具有重大临床意义的合并肺部疾病，包括但不限于： • 存在静息状态下呼吸困难，或患有其他需要持续氧疗的疾病； • 既往或目前患有间质性肺病（ILD）/间质性肺炎、药物性间质性肺病、需要系统性使用类固醇治疗的放射性肺炎，或可疑为间质性肺病等临床表现或高危险因素者； • 严重影响呼吸功能的中重度肺部疾病，如严重的慢性阻塞性肺疾病； • 筛选时有记录的任何自身免疫性、结缔组织或炎症性疾病（如类风湿关节炎、干燥综合征、结节病）引起或怀疑引起肺部受累； • 既往行单侧全肺切除术。 11. 伴有明显症状或不稳定第三间隙积液（如胸腔积液、腹水、心包积液），需要反复引流者。 12. 首次给药前6个月内有胃肠道穿孔和/或瘘管病史，患者存在活动性胃溃疡、十二指肠溃疡、溃疡性结肠炎、胃肠道梗阻或研究者认为可能引起出血或穿孔的胃肠道疾病。 13. 首次给药前出现过严重感染[美国国家癌症研究所不良事件常用术语标准（NCI CTCAE） v5.0 ≥3级]，如需要住院治疗的严重肺炎、菌血症、感染合并症等，或首次给药前2周内出现活动性感染，需要全身治疗者。对于接受预防性抗感染治疗（如预防尿路感染或慢性阻塞性肺疾病加重）的患者，经与申办者讨论后可能有资格入组。 14. 存在人类免疫缺陷病毒（HIV）感染的患者；梅毒抗体阳性且滴度检测阳性的患者。 15. 活动性乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV）感染。活动性HBV定义为乙型肝炎表面抗原（HBsAg）阳性和/或乙肝核心抗体（HBcAb）阳性，且HBV脱氧核糖核酸（DNA）水平高于研究中心的可测量下限；活动性HCV定义为丙型肝炎抗体阳性且HCV核糖核酸（RNA）水平高于研究中心的可测量下限。 16. 既往抗癌治疗的毒性未缓解，定义为毒性（脱发和色素沉着除外）未缓解至NCI CTCAE v5.0 ≤1级、基线水平或入选/排除标准中规定的水平。对于存在慢性2级毒性的患者，如果无症状或使用稳定药物能充分控制，经与申办者讨论后可能有资格入组。 17. 既往对药物有严重过敏反应史（如过敏性休克或之前发生的严重输液反应）。 18. 试验药物首次给药前5年内患有任何其他原发性恶性肿瘤，但经充分切除的基底细胞皮肤癌、宫颈原位癌、甲状腺乳头状癌等恶性程度低的肿瘤除外。 19. 同时参与另外一项临床研究，但观察性（非干预性）临床研究或在干预性研究的随访期内除外。 20. 已知对研究干预或产品的任何辅料过敏的患者。 21. 在首次给药前7天内行妊娠检测证实怀孕或正在哺乳的妇女。 22. 在入组前14天内和研究期间需要使用CYP3A4强效抑制剂（附录 8列出了CYP3A4 强抑制剂或诱导剂）。 23. 任何疾病、医疗状况、系统器官功能障碍或社会状况，包括但不限于精神疾病或药物/酒精滥用，研究者认为可能会干扰患者签署知情同意书的能力、对患者的依从性产生影响、或影响对研究结果的解释。

Exclusion criteria：

Patients must be ineligible if they meet any of the following criteria: Previous/concomitant medications or treatments: 1. History of intolerance to ADC therapy composed of monomethyl auristatin E (MMAE). 2. Inadequate washout period of prior antitumor therapy prior to the first dose, defined as follows: • Any cytotoxic chemotherapy or small molecule targeted therapy <3 weeks or 5 half-lives, whichever is shorter (for treatments involving 5-fluorouracil, leucovorin calcium, and/or paclitaxel regimens, a minimum washout of 2 weeks is required; for nitrosoureas or mitomycin C, a minimum washout of 6 weeks is required); • Antitumor endocrine therapy <3 weeks; • Monoclonal antibody or other biological therapies <3 weeks; • Tyrosine kinase inhibitor therapy <1 week; • Immune therapy or targeted therapy < 4 weeks • Traditional Chinese medicine with antitumor indications (see Appendix 5) <2 weeks; • Wide-field radiotherapy or radiation to more than 30% of the bone marrow for <4 weeks, stereotactic radiotherapy for <2 weeks, whole brain radiotherapy for <2 weeks or stereotactic brain radiotherapy for <1 week, and palliative radiotherapy for <2 weeks. 3. Patients who have undergone major surgery (excluding diagnostic surgery) within 4 weeks prior to first dose or those who plan to undergo major surgery during the study period. Interventional or ablative procedures for tumor treatment within 2 weeks prior to the first dose of the investigational drug. 4. Previous allogeneic bone marrow transplantation or previous solid organ transplantation. 5. Systemic steroid use (>20 mg/day of prednisone or equivalent) or other immunosuppressive treatments within 2 weeks prior to first dose of the investigational drug, with the following exceptions: • Intranasal, inhaled, or local steroid injections (e.g., intra-articular injections); • Physiologic doses of systemic steroids as replacement therapy (e.g., physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency); • Use of steroids to prevent hypersensitivity reactions or to prevent antiemetic (e.g., computed tomography (CT) prophylaxis). 6. Received any live vaccine within 4 weeks prior to the first dose or plan to receive a live vaccine during the study. Medical history and concomitant diseases or examinations: 7. History of leptomeningeal carcinomatosis or carcinomatous meningitis. 8. Brain metastasis or spinal cord compression, except for: • Patients with asymptomatic brain metastases who have non-neoplastic lesions with no enlargement of the lesions and do not therapeutically require immediate local or systemic therapy (e.g., mannitol or corticosteroids) are eligible; • Patients with brain metastases that are stable after treatment of the metastases (brain imaging at least 4 weeks prior to the first dose shows stable lesions, no new neurological symptoms, and no immediate local or systemic treatment is required within 2 weeks prior to the first dose) and no evidence of new or enlarged original brain metastases are eligible; 9. Uncontrolled or clinically significant cardiovascular or cerebrovascular diseases, including but not limited to: • Symptomatic congestive heart failure within 6 months prior to the first dose [New York Heart Association (NYHA) Class II to IV, see Appendix 6], or any history of arterial thromboembolic events (e.g., myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack), or experience of percutaneous coronary angioplasty or coronary artery bypass graft surgery; • History of pulmonary embolism or severe arterial or venous thrombotic events, such as deep vein thrombosis, within 3 months prior to the first dose; • Uncontrolled hypertension that remains unresponsive to a combination of two or more antihypertensive medications, with systolic blood pressure (SBP) >=160 mmHg and/or diastolic blood pressure (DBP) ≥100 mmHg despite antihypertensive treatment. • Other arrhythmias or clinical conditions that the investigator considers may increase the risk of QT interval prolongation, such as complete left bundle branch block, third-degree atrioventricular block, congenital long QT syndrome, severe hypokalemia, family history of long QT syndrome or unexplained sudden death before the age of 40, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia; • Prolongation of the QT interval (QTcF) corrected by the Fridericia formula (see Appendix 7) from a 12-lead ECG to >450 ms (males) or 470 ms (females) at rest (Note: If the first test shows abnormal results, retest twice within 48 h and take the average of the three tests to determine eligibility); • Left ventricular ejection fraction (LVEF) <50% on echocardiography (ECHO). 10. Clinically significant concomitant pulmonary diseases, including but not limited to: • Dyspnea at rest due to advanced malignancy or other conditions requiring continuous oxygen therapy; • Previous or current interstitial lung disease (ILD)/interstitial pneumonia, drug-induced ILD, radiation pneumonitis requiring systemic steroid treatment, or any clinical manifestations or high-risk factors suggestive of ILD; • Moderate to severe pulmonary diseases that significantly impair respiratory function, such as severe chronic obstructive pulmonary disease; • Any documented lung involvement due to, or suspected to be due to, autoimmune, connective tissue, or inflammatory diseases (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis) at the time of screening; • Previous unilateral total pneumonectomy. 11. Patients with symptomatic or unstable third-spacing (e.g., pleural effusion, ascites, pericardial effusion) require repeated drainage. 12. History of gastrointestinal perforation and/or fistula within 6 months prior to the first dose, or the presence of active gastric ulcer, duodenal ulcer, ulcerative colitis, gastrointestinal obstruction, or any other gastrointestinal disease that the investigator deems may cause bleeding or perforation. 13. Patients with severe infection [≥ Grade 3 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0] prior to first dose, such as severe pneumonia, bacteremia, or complications of infection requiring hospitalization; or with active infection requiring systemic treatment within 2 weeks prior to first dose. Patients receiving prophylactic anti-infective treatment (e.g., to prevent urinary tract infections or exacerbations of chronic obstructive pulmonary disease) may be eligible after discussion with the sponsor. 14. Patients with HIV infection or those who test positive for syphilis antibodies with a positive titer test. 15. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Active HBV is defined as positive hepatitis B surface antigen (HBsAg) and/or positive hepatitis B core antibody (HBcAb), with HBV DNA levels above the detectable lower limit of the study site; active HCV is defined as positive hepatitis C antibodies with HCV RNA levels above the detectable lower limit of the study site. 16. Nonremission of toxicity from previous anticancer therapy is defined as nonremission of toxicity (other than alopecia and pigmentation) to NCI CTCAE v5.0 <= Grade 1, baseline, or inclusion/exclusion criteria. Patients with chronic Grade 2 toxicities may be eligible for enrollment if the toxicity is asymptomatic or adequately controlled with stable medication, after discussion with the sponsor. 17. History of severe allergic reactions to drugs (e.g., anaphylactic shock or severe infusion reactions previously experienced). 18. Any other primary malignancy within 5 years prior to first dose of the investigational drug, except for low-risk tumors such as adequately resected basal cell skin cancer, cervical carcinoma in situ, or papillary thyroid carcinoma. Previous/Concurrent Clinical Study Experience 19. Concurrent participation in another clinical study, except for observational (non-interventional) studies or during the follow-up period of an interventional study. 20. Patients with a known allergy to any component of the study intervention or product excipients. Other Exclusions: 21. Women who are pregnant or breastfeeding as confirmed by a pregnancy test within 7 days prior to the first dose. 22. Strong CYP3A4 inhibitors are needed within 14 days prior to enrollment or during the study (potent CYP3A4 inhibitors or inducers are listed in Appendix 8). 23. Any disease, medical condition, organ system dysfunction, or social situation, including but not limited to psychiatric disorders or drug/alcohol abuse, that the investigator believes may interfere with the patient’s ability to sign informed consent, obstacle their compliance, or impact the interpretation of the study results.

研究实施时间：

Study execute time：

从 From 2025-03-11 00:00:00至 To 2028-03-10 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-05-08 00:00:00 至 To 2028-03-10 00:00:00

干预措施：

Interventions：

组别：	A 组	样本量：	1
Group：	Group A	Sample size：	1
干预措施：	0.3mg/kg 加速递增组，入组1例患者，每2周用药一次	干预措施代码：
Intervention：	0.3mg/kg For the accelerated escalation group, one patient was enrolled and administered medication once every two weeks	Intervention code：

组别：	B 组	样本量：	1
Group：	Group B	Sample size：	1
干预措施：	0.6mg/kg为加速递增组，入组1例患者，每2周用药一次	干预措施代码：
Intervention：	0.6mg/kg For the accelerated escalation group, one patient was enrolled and administered medication once every two weeks	Intervention code：

组别：	C 组	样本量：	3
Group：	Group C	Sample size：	3
干预措施：	1.0mg/kg，第1例患者首次给药后观察至少3天且未出现DLT时，方可入组第2例和第3例患者	干预措施代码：
Intervention：	1.0mg/kg,The second and third patients can be enrolled only when the first patient has been observed for at least 3 days after the first administration and no DLT has occurred	Intervention code：

组别：	D 组	样本量：	20
Group：	Group D	Sample size：	20
干预措施：	1.3mg/kg，第1例患者首次给药后观察至少3天且未出现DLT时，方可入组第2例和第3例患者；确认下一剂量组安全后进行剂量扩展，预计扩展入组14-17例。	干预措施代码：
Intervention：	1.3 mg/kg. Only after the first patient has received the drug and has been observed for at least 3 days without any DLT (grade 4 or 5 adverse event), can the second and third patients be enrolled. After confirming the safety of the next dose group, the dose expansion will be carried out. It is expected that 14 to 17 patients will be enrolled in the expansion phase.	Intervention code：

组别：	E 组	样本量：	20
Group：	Group E	Sample size：	20
干预措施：	1.6mg/kg，第1例患者首次给药后观察至少3天且未出现DLT时，方可入组第2例和第3例患者；确认下一剂量组安全后进行剂量扩展，预计扩展入组14-17例。	干预措施代码：
Intervention：	1.6mg/kg. Only when the first patient has received the first dose and has been observed for at least 3 days without any DLT (grade 4 or 5 adverse event) can the second and third patients be enrolled. After confirming the safety of the next dose group, the dose expansion will be carried out. It is expected that 14 to 17 patients will be enrolled in the expansion phase.	Intervention code：

组别：	F 组	样本量：	20
Group：	Group F	Sample size：	20
干预措施：	1.8mg/kg，第1例患者首次给药后观察至少3天且未出现DLT时，方可入组第2例和第3例患者；确认下一剂量组安全后进行剂量扩展，预计扩展入组14-17例。	干预措施代码：
Intervention：	1.8mg/kg. Only after the first patient has received the treatment and has been observed for at least 3 days without any DLT (grade 4 or 5 adverse event), can the second and third patients be enrolled. After confirming the safety of the next dose group, the dose expansion will be carried out. It is expected that 14 to 17 patients will be enrolled in the expansion phase.	Intervention code：

组别：	G 组	样本量：	6
Group：	Group G	Sample size：	6
干预措施：	2.0mg/kg，第1例患者首次给药后观察至少3天且未出现DLT时，方可入组第2例和第3例患者	干预措施代码：
Intervention：	2.0mg/kg ,The second and third patients can be enrolled only when the first patient has been observed for at least 3 days after the first administration and no DLT has occurred	Intervention code：

组别：	H 组	样本量：	24
Group：	Group H	Sample size：	24
干预措施：	在剂量扩展阶段确认剂量的前提下，队列扩展入组：EGFR敏感突变NSCLC1.3mg/kg入组12例，EGFR野生型的NSCLC1.3mg/kg入组12例。	干预措施代码：
Intervention：	On the premise of confirming the dosage during the dose expansion phase, the cohort was expanded for enrollment: 12 cases of EGFR-sensitized mutant NSCLC were enrolled at a dose of 1.3 mg/kg, and 12 cases of EGFR wild-type NSCLC were also enrolled at the same dose.	Intervention code：

组别：	I 组	样本量：	25
Group：	Group I	Sample size：	25
干预措施：	在剂量扩展阶段确认剂量后，队列进行了扩大以纳入更多患者：12名结直肠癌（CRC）患者以1.6 mg/kg的剂量入组，13名其他实体瘤患者也以相同剂量入组。	干预措施代码：
Intervention：	On the premise of confirming the dosage during the dose expansion phase, the cohort was expanded for enrollment: 12 CRC patients were enrolled at a dose of 1.6 mg/kg, and 13 patients with other solid tumors were enrolled at the same dose.	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(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海东方医院	单位级别：	三甲
Institution hospital：	Shanghai East Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	上海	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海仁济医院	单位级别：	三甲
Institution hospital：	Shanghai Renji Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	上海	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海肺科医院	单位级别：	三甲
Institution hospital：	Shanghai Pulmonary Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	浙江	市(区县)：
Country：	China	Province：	Zhejiang	City：
单位(医院)：	浙江省肿瘤医院	单位级别：	三甲
Institution hospital：	Zhejiang Cancer Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	山东	市(区县)：
Country：	China	Province：	Shandong	City：
单位(医院)：	临沂市肿瘤医院	单位级别：	三甲
Institution hospital：	Linyi Cancer Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	黑龙江	市(区县)：
Country：	China	Province：	Heilongjiang	City：
单位(医院)：	哈尔滨医科大学肿瘤医院	单位级别：	三甲
Institution hospital：	Harbin Medical University Cancer Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	广东	市(区县)：
Country：	China	Province：	Guangdong	City：
单位(医院)：	南方医科大学附属南方医院	单位级别：	三甲
Institution hospital：	Nanfang Hospital, Southern Medical University	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	江苏	市(区县)：
Country：	China	Province：	Jiangsu	City：
单位(医院)：	泰州市人民医院	单位级别：	三甲
Institution hospital：	Taizhou People's Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	剂量限制性毒性（DLT）在DLT观察期内的发生率	指标类型：	主要指标
Outcome：	Incidence of dose-limiting toxicities (DLTs) during the DLT observation period	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	不良事件（AE）的发生率和严重程度	指标类型：	主要指标
Outcome：	Incidence and severity of adverse events (AEs)	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	生物标志物	指标类型：	次要指标
Outcome：	Biomarker	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	客观缓解率	指标类型：	次要指标
Outcome：	Objective response rate	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	中位无进展生存期	指标类型：	次要指标
Outcome：	Median progression-free survival	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：	10张肿瘤组织切片
Sample Name：	Blood	Tissue：	10 of Tumor Tissue slides
人体标本去向	使用后销毁	说明	检测后剩余样本科医联创实验室保存至试验药物上市后5年
Fate of sample：	Destruction after use	Note：	The remaining samples after testing preserved by Keyi Lianchuang Laboratory shall be stored under specific conditions.

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：

正在进行

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）：

无

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

NO

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：
Blinding：

是否共享原始数据： IPD sharing	是Yes
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）：	研究公开发表后半年，邮件联系研究负责人合理获取。
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Six months after the publication of the research, contact the research leader via email to obtain reasonable information.
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：	电子采集和管理系统
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Electronic Data Capture, EDC
数据与安全监察委员会： Data and Safety Monitoring Committee：	暂未确定/Not yet
注册人： Name of Registration：	2026-01-05 17:51:47