注册号：
Registration number：
ChiCTR2500114728 最近更新日期：
Date of Last Refreshed on：
2025-12-17 09:38:12 注册时间：
Date of Registration：
2025-12-17 00:00:00 注册号状态：
补注册Registration Status：
Retrospective registration注册题目：
ZG005 联合盐酸吉卡昔替尼片在复发或难治性淋巴瘤患者中的多中心、开放、剂量探索和剂量扩展的 I/II 期临床研究Public title：
ZG005 combination hydrochloride gilteritinib tablets in patients with relapsed or refractory lymphoma: a multicentre, open-label, dose-exploration and dose-expansion phase I/II clinical study.注册题目简写：English Acronym：研究课题的正式科学名称：
ZG005 联合盐酸吉卡昔替尼片在复发或难治性淋巴瘤患者中的多中心、开放、剂量探索和剂量扩展的 I/II 期临床研究Scientific title：
ZG005 combination hydrochloride gilteritinib tablets in patients with relapsed or refractory lymphoma: a multicentre, open-label, dose-exploration and dose-expansion phase I/II clinical study.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：
贾双羽
研究负责人：
金洁 Applicant：
Shuangyu Jia
Study leader：
Jie Jin 申请注册联系人电话：
Applicant telephone：
+86 18039230612
研究负责人电话：
Study leader's telephone：
+86 13505716779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：
jiasy@zelgen.com
研究负责人电子邮件：
Study leader's E-mail：
jiej0503@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：
上海市浦东新区蔡伦路999号1号楼2层
研究负责人通讯地址：
浙江省杭州市庆春路79号Applicant address：
No.999 Cai Lun Road, Building 1, 2nd Floor, Pudong New Area, Shanghai.
Study leader's address：
No. 79, Qingchun Road, Hangzhou City, Zhejiang Province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：
苏州泽璟生物制药股份有限公司Applicant's institution：
Suzhou Zelgen Biopharmaceuticals Co., Ltd研究负责人所在单位：
浙江大学医学院附属第一医院Affiliation of the Leader：
The First Affiliated Hospital of Zhejiang University School of Medicine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伦审第(109)号
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：
浙江大学医学院附属第一医院以注册为目的的临床试验伦理审查委员会Name of the ethic committee：
Clinical Trial Ethics Committee of the Affiliated Hospital College of Medicine, Zhejiang University伦理委员会批准日期：
Date of approved by ethic committee：
2025-02-27 00:00:00伦理委员会联系人：
周惠丽Contact Name of the ethic committee：
Huili Zhou伦理委员会联系地址：
浙江省杭州市庆春路79号Contact Address of the ethic committee：
No. 79, Qingchun Road, Hangzhou City, Zhejiang Province伦理委员会联系人电话：
Contact phone of the ethic committee：
+86 571 87236685
伦理委员会联系人邮箱：
Contact email of the ethic committee：
huilizhou1980@163.com研究实施负责（组长）单位：
浙江大学医学院附属第一医院Primary sponsor：
The First Affiliated Hospital of Zhejiang University School of Medicine研究实施负责（组长）单位地址：
浙江省杭州市庆春路79号Primary sponsor's address：
No. 79, Qingchun Road, Hangzhou City, Zhejiang Province试验主办单位(项目批准或申办者)：
Secondary sponsor：
国家：
中国
省(直辖市)：
浙江省
市(区县)：
Country：
China
Province：
Zhejiang
City：
单位(医院)：
浙江大学医学院附属第一医院
具体地址：
浙江省杭州市庆春路79号
Institution
hospital：
The First Affiliated Hospital of Zhejiang University School of Medicine
Address：
No. 79, Qingchun Road, Hangzhou City, Zhejiang Province经费或物资来源：
苏州泽璟生物制药股份有限公司Source(s) of funding：
Suzhou Zelgen Biopharmaceuticals Co., Ltd研究疾病：
经典型霍奇金淋巴瘤；纵膈大 B 细胞淋巴瘤；结外 NK/T 细胞淋巴瘤 Target disease：
Classical Hodgkin lymphoma; mediastinal large B-cell lymphoma; extranodal NK/T-cell lymphoma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：
随机平行对照 Study design：
Parallel 研究目的：
主要目的
PART 1：
（1）探索 ZG005 联合盐酸吉卡昔替尼片在复发或难治性淋巴瘤患者中的安全性；
（2）确认用于复发或难治性淋巴瘤的 II 期推荐给药方案。
PART 2：
评价 ZG005 联合盐酸吉卡昔替尼片在复发或难治性淋巴瘤的有效性。
次要目的
PART 1：
（1）评价 ZG005 联合盐酸吉卡昔替尼方案的中 ZG005 和盐酸吉卡昔替尼片的人体药代动力学特征；
（2）评价 ZG005 联合盐酸吉卡昔替尼方案在复发或难治性淋巴瘤的有效性；
（3）评价 ZG005 的免疫原性；
（4）如数据允许，评估生物标志物表达水平与疗效的相关性。
PART 2：
（1）评价 ZG005 联合盐酸吉卡昔替尼方案的安全性及其他有效性指标；
（2）评价 ZG005 的免疫原性；
（3）如数据允许 ， 基 于 群 体 PK 分 析 方 法 ， 表 征 ZG005 的 PK特征 ；
（4）如数据允许，评估生物标志物表达水平与疗效的相关性。
Objectives of Study：
Main purpose
PART 1
(1) To explore the safety of ZG005 combined with gicaxitinib hydrochloride tablets in patients with relapsed or refractory lymphoma;
(2) Confirm the phase II recommended dosing regimen for relapsed or refractory lymphoma.
PART 2
To evaluate the efficacy of ZG005 combined with gicaxitinib hydrochloride tablets in the treatment of relapsed or refractory lymphoma.
Secondary purpose
PART 1
(1) To evaluate the pharmacokinetic characteristics of ZG005 and gicaxitinib hydrochloride tablets in the ZG005 combined with gicaxitinib hydrochloride regimen;
(2) To evaluate the efficacy of the ZG005 combined with gicaxitinib hydrochloride regimen in relapsed or refractory lymphoma;
(3) Evaluate the immunogenicity of ZG005;
(4) If the data permit, evaluate the correlation between the expression levels of biomarkers and therapeutic efficacy.
PART 2
(1) Evaluate the safety and other efficacy indicators of the ZG005 combined with gicaxitinib hydrochloride regimen;
(2) Evaluate the immunogenicity of ZG005;
(3) If the data permits, based on the group PK analysis method, characterize the PK features of ZG005;
(4) If the data permit, evaluate the correlation between the expression levels of biomarkers and therapeutic efficacy.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. 对本试验已充分了解并自愿签署知情同意书；
2. 签署 ICF 时，年龄>=18 岁，性别不限；
3. 经组织学确诊的复发或难治性淋巴瘤：• 经典型霍奇金淋巴瘤：复发/难治的定义需符合以下要求之一：（1）挽救化疗后接受自体干细胞移植，之后复发或进展；（2）对于未接受自体干细胞移植的受试者，则要求：一线化疗须为全身多药联合化疗。对于难治患者，指疗程>=2 周期未达到 PR；或者疗程>=4 周期未达 CR；如最佳疗效或结束原因为 PD，则疗程数不作要求。对于复发患者，复发前近期内至少接受过一线化疗。 • 纵膈大 B 细胞淋巴瘤：诊断为复发或难治性原发性纵隔大 B 细胞淋巴瘤（复发：在最近的治疗中获得缓解后疾病出现进展，难治：在最近的治疗中未能获得 CR 或PR），且： 自体干细胞移植后复发，或在自体干细胞移植后60 天内未获得 CR 或 PR。受试者可能在自体干细胞移植后因复发或难治性疾病接受过干预治疗，在这种情况下，受试者必须在上次治疗后复发或难治。 不符合自体造血干细胞移植条件的受试者，既往至少接受过>=2 种治疗，且对最后一线治疗无应答或在最后一线治疗后复发。对于在全身治疗后接受局部巩固放疗的参与者，局部放疗将不被视为单独的治疗方案。 曾在既往治疗中使用过利妥昔单抗。 • 结外 NK/T 细胞淋巴瘤：在接受门冬酰胺酶基础的化疗基础上（I/II 期必须放疗），复发难治性的定义：复发指在达到 CR 后，原发部位或其他部位出现新的病变；难治性指以下任一项：2 个治疗周期后出现 PD，4 个治疗周期未达到 PR，或 6 个治疗周期仍未达到 CR。自体干细胞移植后没有应答、或疾病复发或疾病进展的患者可以入组。
4. 受试者须愿意提供既往骨髓活检的病理学检查结果，可接受最近一次复发时的历史病理活检结果，但该次复发到开始研究治疗前疾病没有缓解（仅接受入组治疗前 3 个月内的既往病理诊断结果），或愿意在筛选时接受骨髓穿刺和骨髓活检，且愿意在接受治疗后进行骨髓穿刺和骨髓活检（对于基线骨髓活检阳性的患者在治疗期间出现完全的影像学缓解，则需要进行骨髓活检，并应在影像学评估后的 2 周内完成）；
5. 先前接受过抗PD-(L)1治疗且治疗失败的患者（包括抗PD-(L)1治疗原发耐药和继发耐药的患者）。抗PD-(L)1治疗耐药的定义：• 原发耐药：药物暴露>=6 周，但最佳反应 PD 或 SD（＜6个月）后出现 PD。• 继发耐药：最佳反应可以为 CR，PR 或 SD（＞6 个月），然后出现 PD。
6. 既往至少经过两种先前治疗失败（包括 PD- (L)1 治疗）；
7. 至少有一个影像学可测量的肿瘤病灶（长径＞15mm的淋巴结病灶或长径＞10mm的结外病灶），且该病灶经FDG-PET诊断阳性。对于既往进行过放射性治疗的病灶，仅当该病灶在放疗后出现明确疾病进展，才可将该病灶纳入靶病灶；
8. ECOG评分0或1分；
9. 预期生存期大于12周；
10. 已从既往治疗的不良反应中恢复至CTCAE 5.0标准<=1级或基线水平（研究者判断无安全风险的毒性除外，如脱发、可激素替代治疗的甲状腺功能低下等）；
11. 受试者24周内没有进行干细胞移植计划（符合条件并愿意接受自体移植的患者不应参加这项试验）；
12. 有生育能力的女性受试者在研究药物首次给药前7天内的血妊娠结果为阴性；男性受试者和女性受试者（除非为绝经后、手术绝育）及伴侣，均必须在研究期间及停止治疗后6个月内采取至少1种医学认可有效的避孕方法；Inclusion criteria
1. Have fully understood this trial and voluntarily signed the informed consent form;
2. At the time of signing the ICF, the age should be at least 18 years old, and there is no gender restriction.
3. Histologically confirmed relapsed or refractory lymphoma: • Classical Hodgkin's lymphoma: The definition of relapsed/refractory must meet one of the following requirements: (1) Relapse or progression follows autologous stem cell transplantation after salvage chemotherapy; (2) For subjects who have not received autologous stem cell transplantation, it is required that the first-line chemotherapy must be a combination of systemic multi-drug chemotherapy. For refractory patients, it refers to those who have not achieved PR after a treatment course of more than or equal to 2 cycles. Or the treatment course is greater than or equal to 4 cycles without achieving complete remission (CR). If the best therapeutic effect or the cause of termination is PD, the number of treatment courses is not required. For patients with recurrence, they should have received at least one line of chemotherapy in the recent period before recurrence. • Mediastinal large B-cell lymphoma: Diagnosed as relapsed or refractory primary mediastinal large B-cell lymphoma (relapse: disease progression after achieving remission in recent treatment; refractory: failure to achieve CR or PR in recent treatment), and: Recurrence after autologous stem cell transplantation, or failure to achieve complete remission (CR) or complete remission (PR) within 60 days after autologous stem cell transplantation. The subject may have received intervention treatment for relapsed or refractory diseases after autologous stem cell transplantation. In such cases, the subject must have relapsed or been refractory after the last treatment. Subjects who do not meet the conditions for autologous hematopoietic stem cell transplantation have received at least two previous treatments and have not responded to the last line of treatment or have relapsed after the last line of treatment. For participants who received local consolidation radiotherapy after systemic treatment, local radiotherapy will not be regarded as a separate treatment option. Rituximab has been used in previous treatments. • Extranodal NK/ T-cell lymphoma: On the basis of chemotherapy based on asparaginase (radiotherapy is necessary for stage I/II), the definition of relapse and refractory: Relapse refers to the appearance of new lesions at the primary site or other sites after achieving complete remission (CR). Refractory refers to any of the following: PD occurs after 2 treatment cycles, PR is not achieved after 4 treatment cycles, or CR is still not achieved after 6 treatment cycles. Patients who have not responded to autologous stem cell transplantation, or have a recurrence or progression of the disease can be enrolled.
4. The subjects must be willing to provide the pathological examination results of previous bone marrow biopsies. They can accept the historical pathological biopsy results at the time of the most recent recurrence, but the disease did not improve before the start of the study treatment (only previous pathological diagnosis results within 3 months before enrollment in the treatment will be accepted), or be willing to undergo bone marrow puncture and bone marrow biopsy at the time of screening. And be willing to undergo bone marrow puncture and bone marrow biopsy after receiving treatment (for patients with positive baseline bone marrow biopsy who achieve complete imaging remission during treatment, bone marrow biopsy is required and should be completed within 2 weeks after imaging assessment);
5. Patients who have previously received anti-PD -(L)1 treatment and failed (including those with primary and secondary resistance to anti-PD -(L)1 treatment). The definition of anti-PD -(L)1 treatment resistance: • Primary resistance: Drug exposure >=6 weeks, but PD or SD (< 6 months) occurs after the best response. Secondary drug resistance: The optimal response can be CR, PR or SD (> 6 months), followed by PD.
6. At least two previous treatment failures (including PD- (L)1 treatment) in the past;
7. There should be at least one radiologically measurable tumor lesion (lymph node lesion with a long diameter > 15mm or extranodal lesion with a long diameter > 10mm), and this lesion should be diagnosed positively by FDG-PET. For lesions that have undergone radiotherapy in the past, they can only be included as target lesions if there is a clear disease progression after radiotherapy.
8. ECOG score: 0 or 1 point;
9. The expected survival period is greater than 12 weeks;
10. Has recovered from the adverse reactions of previous treatment to CTCAE 5.0 standard <=1 or baseline level (except for toxicities that the researcher judged as having no safety risk, such as alopecia, hypothyroidism that can be treated with hormone replacement therapy, etc.);
11. The subjects did not have a stem cell transplantation plan within 24 weeks (patients who are eligible and willing to receive autologous transplantation should not participate in this trial);
12. The blood pregnancy results of fertile female subjects within 7 days before the first administration of the study drug were negative; Male and female subjects (unless they are postmenopausal or have undergone surgical sterilization) and their partners must use at least one medically recognized and effective contraceptive method during the study period and within six months after the cessation of treatment.排除标准：
1.已知累及中枢神经系统的淋巴瘤；
2.结节性淋巴细胞为主型的霍奇金淋巴瘤（适用于霍奇金淋巴瘤）；
3.侵袭性NK细胞白血病（适用于NK/T细胞淋巴瘤）；
4.初诊NKTCL时存在重度嗜血细胞综合征（适用于NK/T细胞淋巴瘤）；
5.肺部大血管受侵者；
6.研究药物首次给药前7天内（且14天内未接受输血、EPO、G-CSF、血小板生成因子及血小板输注），符合下列任何一项或多项标准：6.1 血常规：中性粒细胞计数<1.0×10^9 /L，血小板<75×10^9 /L，血红蛋白<80g/L； 6.2 肝功能：谷丙转氨酶（ALT）或谷草转氨酶（AST）>=2.5×ULN；总胆红素（TBIL）>=1.5×ULN； 6.3 肌酐＞1.5×ULN，或根据Cockcroft-Gault公式计算的肌酐清除率<50 mL/min（计算公式详见13.1附录A）； 6.4 国际标准化比率（INR）>1.5，或活化部分凝血酶原时间（APTT）>1.5×ULN。
7.任何显著的临床和实验室异常，研究者认为影响安全性评价者，如：控制不佳的糖尿病（空腹血糖＞8.9mmol/L）；周围神经病变（NCI- CTC AE v5.0 标准2级或以上）；
8.有临床症状的甲状腺功能异常，且经治疗无法控制；
9.既往接受免疫检查点抑制剂治疗出现过>=3 级或导致药物永久停用的 irAE，或发生过>=2 级免疫相关心脏毒性；
10.存在临床无法控制的第三间隙积液（如积液引流无法控制的胸水、腹水）；
11.接受以下任何治疗的患者： 11.1 既往口服JAK抑制剂治疗>=7天者； 11.2 在研究药物首次给药前 14 天内或正在接受全身应用的（口服或静脉）免疫调节药物或皮质类固醇药物（强的松>10 mg/天或等效剂量）； 11.3 在研究药物首次给药前 4 周内接受过化疗、放疗、免疫检查点抑制剂治疗、抗体偶联复合物治疗或其他抗肿瘤治疗者；在首次给药前 6 周内接受了亚硝基脲或丝裂霉素 C 的治疗；11.4 在研究药物首次给药前 90 天内接受肿瘤抗原疫苗治疗者；首次给药前 4 周内接种过任何减毒活疫苗，或计划在研究期间接种减毒活疫苗； 11.5 在研究药物首次给药前 2 周（或 5 个半衰期，以时间较长者为准）内系统性使用过 CYP 3A4 强效抑制剂或氟康唑等（注：允许使用上述局部外用药）），以及因伴随疾病需要持续使用此类药物者； 11.6 在研究药物首次给药前90天内进行自体造血干细胞移植者；11.7 既往接受过同种异体造血干细胞移植者或实质器官移植者；11.8 在研究药物首次给药前 4 周内接受过重大外科手术、有重大创伤、研究过程中预计进行重大外科手术者；
12.五年内患有任何其他恶性肿瘤（除外已根治性切除且未复发的皮肤基底细胞癌、皮肤鳞状细胞癌、浅表性膀胱癌、局部前列腺癌、原位宫颈癌或其他原位癌）；
13.有自身免疫疾病病史，包括但不限于系统性红斑狼疮、肾炎、银屑病、类风湿性关节炎、炎性肠道疾病、自身免疫性肝炎（除外以下：仅需胰岛素替代治疗的I型糖尿病、仅需甲状腺激素替代治疗的免疫性甲状腺炎、无需全身治疗的皮肤病（如白癜风）、已控制的乳糜泻、童年患哮喘成人后完全缓解无需任何干预）；
14.患有严重的心脑血管疾病，包括但不限于以下情况： 14.1 研究药物首次给药前6个月内，患有急性心肌梗塞、不稳定性心绞痛、中风，接受过冠状动脉成形术或支架； 14.2 纽约心脏病协会III级或IV级充血性心力衰竭或左室射血分数（LVEF）＜50%； 14.3 未能控制的高血压（尽管使用了最优治疗，但收缩压>=140mmHg和/或舒张压>=90 mmHg）； 14.4 >2级的心律失常（CTCAE v5.0）； 14.5 基线期心电图QTc间期延长（Fridericia方法，QTcF>480 ms）；14.6 在研究药物首次给药前 90 天存在深静脉血栓、肺栓塞或其他严重血栓栓塞事件病史(植入式输液港或导管相关血栓，或浅表静脉血栓不视为严重血栓栓塞)。
15.有需使用类固醇或抗纤维化治疗的(非感染性)肺炎病史者或当前肺炎者；
16.在研究药物首次给药前12个月内有活动性结核病感染史的患者；筛选期确诊为潜伏性结核感染者（潜伏性结核感染者如同意接受异烟肼单药预防性治疗可纳入）；
17.当前患有严重影响吞咽药物的疾病；
18.存在活动性感染（例如急性细菌感染、病毒、活动性梅毒等）或在研究药物首次给药前14天内或正在接受静脉输注抗生素： 18.1 活动性丙型肝炎定义为：丙型肝炎抗体阳性且HCV-RNA阳性； 18.2 活动性人类免疫缺陷病毒感染定义为：人类免疫缺陷病毒抗体阳性； 18.3 活动性乙型肝炎定义为：乙型肝炎病毒滴度>=500 IU /mL（对于慢性乙肝患者，需满足首次给药前抗HBV治疗至少14天且同意研究期间继续抗病毒治疗）。
19.已知对试验药物或其任何辅料过敏；对人源化抗体或融合蛋白产生重度变态反应、类过敏或其它超敏反应病史或疑似对盐酸吉卡昔替尼或同类药物过敏者；
20. 既往有明确的神经或精神障碍史，包括癫痫或痴呆；
21.研究者认为受试者存在其他原因而不适合参加本临床研究。Exclusion criteria：
1.Lymphoma known to involve the central nervous system;
2. Nodular lymphocyte-predominant Hodgkin's lymphoma (applicable to Hodgkin's lymphoma);
3. Aggressive NK cell leukemia (applicable to NK/ T-cell lymphoma);
4. At the initial diagnosis of NKTCL, there was severe hemophagocytic syndrome (applicable to NK/ T-cell lymphoma);
5. Those whose major blood vessels in the lungs have been invaded;
6. Within 7 days before the first administration of the study drug (and without receiving blood transfusion, EPO, G-CSF, platelet-generating factor and platelet transfusion within 14 days), meet any one or more of the following criteria: 6.1 Blood routine: Neutrophil count <1.0×10^9 /L, platelet count <75×10^9 /L, hemoglobin <80g/L; 6.2 Liver function: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >=2.5×ULN; Total bilirubin (TBIL) >=1.5×ULN; 6.3 Creatinine > 1.5×ULN, or creatinine clearance rate calculated according to the Cockcroft-Gault formula <50 mL/min (for the calculation formula, see Appendix A of 13.1); 6.4 International Normalized Ratio (INR) >1.5, or activated partial prothrombin time (APTT) >1.5×ULN.
7. Any significant clinical and laboratory abnormalities that the researchers consider to affect the safety assessment, such as: poorly controlled diabetes (fasting blood glucose > 8.9mmol/L); Peripheral neuropathy (NCI-CTC AE v5.0 standard grade 2 or above);
8. Thyroid dysfunction with clinical symptoms that cannot be controlled after treatment;
9. Previous treatment with immune checkpoint inhibitors has led to grade 3 irAE or permanent drug discontinuation, or has experienced grade 2 immune-related cardiotoxicity;
10. There is clinically uncontrollable third space effusion (such as pleural effusion and ascites that cannot be controlled by effusion drainage);
11. Patients who have received any of the following treatments: 11.1 Those who have previously received oral JAK inhibitor treatment for >=7 days; 11.2 Within 14 days prior to the first administration of the study drug or currently receiving systemic (oral or intravenous) immunomodulatory drugs or corticosteroids (prednisone >10 mg/ day or equivalent dose); 11.3 Those who have received chemotherapy, radiotherapy, immune checkpoint inhibitor therapy, antibody-drug conjugate complex therapy or other anti-tumor treatments within 4 weeks prior to the first administration of the study drug; Received nitrosamuridine or mitomycin C treatment within 6 weeks before the first administration; 11.4 Those who received tumor antigen vaccine treatment within 90 days before the first administration of the study drug; Have received any live attenuated vaccine within 4 weeks before the first administration, or plan to receive a live attenuated vaccine during the study period; 11.5 Those who have systematically used a potent CYP 3A4 inhibitor or fluconazole, etc. (Note: The above topical medications are allowed) within 2 weeks (or 5 half-lives, whichever is longer) before the first administration of the study drug, and those who need to continue using such drugs due to concomitant diseases; 11.6 Those who have undergone autologous hematopoietic stem cell transplantation within 90 days before the first administration of the study drug; 11.7 Those who have received allogeneic hematopoietic stem cell transplantation or parenchymal organ transplantation in the past; 11.8 Those who have undergone major surgical operations within 4 weeks prior to the first administration of the study drug, have suffered major trauma, or are expected to undergo major surgical operations during the study process;
12. Having suffered from any other malignant tumor within five years (excluding cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, superficial bladder cancer, local prostate cancer, cervical cancer in situ or other cancers in situ that have been radically resected and have not recurred);
13. Have a history of autoimmune diseases, including but not limited to systemic lupus erythematosus, nephritis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, and autoimmune hepatitis (excluding the following: Type 1 diabetes that only requires insulin replacement therapy, immune thyroiditis that only requires thyroid hormone replacement therapy, skin diseases (such as vitiligo) that do not require systemic treatment, controlled celiac disease, and childhood asthma that is completely relieved in adulthood without any intervention.
14. Suffering from severe cardiovascular and cerebrovascular diseases, including but not limited to the following situations: 14.1 Within 6 months prior to the first administration of the study drug, having suffered from acute myocardial infarction, unstable angina pectoris, stroke, and having undergone coronary angioplasty or stenting; 14.2 New York Heart Association grade III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 50%; 14.3 Uncontrolled hypertension (systolic blood pressure >=140mmHg and/or diastolic blood pressure >=90 mmHg despite optimal treatment); 14.4 > grade 2 arrhythmia (CTCAE v5.0); 14.5 Prolonged QTc interval of baseline electrocardiogram (Fridericia method, QTcF>480 ms); 14.6 There is a history of deep vein thrombosis, pulmonary embolism or other serious thromboembolic events 90 days before the first administration of the study drug (thrombosis related to implantable infusion ports or catheters, or superficial vein thrombosis is not regarded as serious thromboembolism).
15. Those with a history of (non-infectious) pneumonia requiring steroid or anti-fibrotic treatment, or those currently having pneumonia;
16. Patients with a history of active tuberculosis infection within 12 months prior to the first administration of the study drug; During the screening period, those diagnosed as latent tuberculosis carriers (latent tuberculosis carriers who agree to receive isoniazid monotherapy for preventive treatment can be included);
17. Currently suffering from a disease that seriously affects the swallowing of medication;
18. Presence of active infection (such as acute bacterial infection, viral, active syphilis, etc.) or within 14 days before the first administration of the study drug or currently receiving intravenous antibiotic infusion: 18.1 Active hepatitis C is defined as: positive hepatitis C antibody and positive HCV-RNA; 18.2 Active human immunodeficiency virus infection is defined as: positive for human immunodeficiency virus antibodies; 18.3 Active hepatitis B is defined as: hepatitis B virus titer >=500 IU /mL (for patients with chronic hepatitis B, it is necessary to meet the requirement of at least 14 days of anti-HBV treatment before the first administration and agree to continue antiviral treatment during the study period).
19. Known to be allergic to the investigational drug or any of its excipients; Those with a history of severe allergic reactions, hypersensitivity or other hypersensitivity reactions to humanized antibodies or fusion proteins, or suspected allergic reactions to gicaxitinib hydrochloride or similar drugs;
20. There is a clear history of neurological or mental disorders in the past, including epilepsy or dementia;
21. The researchers believe that the subjects have other reasons that make them unsuitable to participate in this clinical study.研究实施时间：
Study execute time：
从
From
2025-04-21 00:00:00至
To
2027-04-21 00:00:00
征募观察对象时间：
Recruiting time：
从
From
2025-04-28 00:00:00
至
To
2026-04-21 00:00:00干预措施：
Interventions：
组别：
Part1-方案 B
样本量：
20
Group：
Part1-Option B
Sample size：
干预措施：
ZG005 20 mg/kg Q3w 吉卡昔替尼 100 mg Bid（D1-D7、CnD1-D14）
干预措施代码：
Intervention：
ZG005 20 mg/kg Q3w GDC-0994 100 mg Bid (D1-D7, CnD1-D14)
Intervention code：
组别：
Part1-方案 A
样本量：
20
Group：
Part-1-Option A
Sample size：
干预措施：
ZG005 20 mg/kg Q3w 吉卡昔替尼 100 mg Bid（D1-治疗结束）
干预措施代码：
Intervention：
ZG005 20 mg/kg Q3w giredestrant 100 mg bid (D1 to end of treatment)
Intervention code：
组别：
Part2-扩展研究
样本量：
20
Group：
Part2-Extended research
Sample size：
干预措施：
ZG005 20 mg/kg Q3w 吉卡昔替尼 100 mg Bid（D1-治疗结束）或或ZG005 20 mg/kg Q3w 吉卡昔替尼 100 mg Bid（D1-D7、CnD1-D14）
干预措施代码：
Intervention：
ZG005 20 mg/kg Q3w GDC-0994 100 mg Bid (D1-D7, CnD1-D14) Or ZG005 20 mg/kg Q3w GDC-0994 100 mg Bid (D1-D7, CnD1-D14)ZG005 20 mg/kg Q3w GDC-0994 100 mg
Intervention code：研究实施地点：
Countries of recruitment and research settings：
国家：
中国
省(直辖市)：
浙江省
市(区县)：
Country：
China
Province：
Zhejiang
City：
单位(医院)：
浙江大学医学院附属第一医院
单位级别：
三级甲等
Institution
hospital：
The FIrst Affiliated Hospital, College of Medicine, Zhejiang University
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)：
长沙泰和医院
单位级别：
三级
Institution
hospital：
Changsha Taihe Hospital
Level of the institution：
Tertiary
国家：
中国
省(直辖市)：
山东省
市(区县)：
Country：
China
Province：
Shandong
City：
单位(医院)：
临沂市肿瘤医院
单位级别：
三级甲等
Institution
hospital：
Linyi Tumor Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
安徽省
市(区县)：
Country：
China
Province：
Anhui
City：
单位(医院)：
安徽省肿瘤医院
单位级别：
三级甲等
Institution
hospital：
Anhui Provincial Cancer Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
辽宁省
市(区县)：
Country：
China
Province：
Liaoning
City：
单位(医院)：
中国医科大学附属盛京医院
单位级别：
三级甲等
Institution
hospital：
Shengjing Hospital of China Medical University
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
黑龙江省
市(区县)：
Country：
China
Province：
Heilongjiang
City：
单位(医院)：
哈尔滨医科大学附属肿瘤医院
单位级别：
三级甲等
Institution
hospital：
harbin medical university cancer 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：
HenanCancerHospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
浙江省
市(区县)：
Country：
China
Province：
Zhejiang
City：
单位(医院)：
浙江大学医学院附属第二医院
单位级别：
三级甲等
Institution
hospital：
The second affiliated hospital of Zhejiang University school of medicine
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)：
江苏省
市(区县)：
Country：
China
Province：
Jiangsu
City：
单位(医院)：
南京鼓楼医院
单位级别：
三级甲等
Institution
hospital：
Drum Tower Hospital
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
浙江省
市(区县)：
Country：
China
Province：
Zhejiang
City：
单位(医院)：
温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 Wenzhou Medical University
Level of the institution：
Tertiary A
国家：
中国
省(直辖市)：
陕西省
市(区县)：
Country：
China
Province：
Shaanxi
City：
单位(医院)：
西安交通大学第二附属医院
单位级别：
三级甲等
Institution
hospital：
Xi'an Jiaotong University Second Affiliated Hospital
Level of the institution：
Tertiary A测量指标：
Outcomes：
指标中文名：
药代动力学浓度分析集
指标类型：
次要指标
Outcome：
PKCS，Pharmacokinetic ConcentrationAnalysis Set
Type：
Secondary indicator
测量时间点：
测量方法：
Measure time point of outcome：
Measure method：
指标中文名：
有效性终点
指标类型：
次要指标
Outcome：
Effectiveness endpoints
Type：
Secondary indicator
测量时间点：
测量方法：
Measure time point of outcome：
Measure method：
指标中文名：
LYRIC 标准评价的客观缓解率（ORR）
指标类型：
主要指标
Outcome：
Objective response rate (ORR) as assessed by LYRIC criteria.
Type：
Primary indicator
测量时间点：
测量方法：
Measure time point of outcome：
Measure method：
指标中文名：
免疫原性评价指标
指标类型：
次要指标
Outcome：
Immunogenicity evaluation index
Type：
Secondary indicator
测量时间点：
测量方法：
Measure time point of outcome：
Measure method：
指标中文名：
安全性
指标类型：
主要指标
Outcome：
Security
Type：
Primary 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：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）：
由研究者采用EDC中的随机系统随机分组。Randomization Procedure (please state who
generates the
random number sequence and by what method)：
The researchers randomly assigned groups using a random system in EDC.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
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）：
研究结束后，通过ResMan(www.medresman.org.cn)方式共享The way of sharing IPD”(include metadata and
protocol,
If use web-based public database, please provide
the
url)：
After the end of the study, it was shared by ResMan (www.medresman.org.cn).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：
CRF;EDCData collection and Management (A
standard data collection and management system
include a CRF and an electronic data capture：
CRF;EDC数据与安全监察委员会：
Data and Safety Monitoring Committee：
有/Yes注册人：
Name of Registration：
2025-12-17 09:38:05
