ChiCTR2500103430 版本V1.0 版本创建时间2025/05/29 09:38:25 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2500103430 

最近更新日期：

Date of Last Refreshed on：

 2025-05-29 09:38:16 

注册时间：

Date of Registration：

 2025-05-29 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

一项评价GH2616 片在晚期实体瘤受试者中的安全性、耐受性、药代动力学、药效动力学和初步疗效的剂量递增、剂量扩展的Ia/Ib期临床研究（方案编号：GH2616-101）

Public title：

A Dose-Escalation, Dose-Expansion Phase Ia/Ib Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of GH2616 Tablets in Subjects With Advanced Solid Tumors(StudyID:GH2616-101)

注册题目简写：

GH2616 晚期实体瘤的 Ia/Ib 期临床研究

English Acronym：

Phase Ia/Ib clinical study of GH2616 advanced solid tumors

研究课题的正式科学名称：

一项评价GH2616 片在晚期实体瘤受试者中的安全性、耐受性、药代动力学、药效动力学和初步疗效的剂量递增、剂量扩展的Ia/Ib期临床研究（方案编号：GH2616-101）

Scientific title：

A Dose-Escalation, Dose-Expansion Phase Ia/Ib Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of GH2616 Tablets in Subjects With Advanced Solid Tumors(StudyID:GH2616-101)

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：

陈诗雅 

研究负责人：

宋正波 

Applicant：

Shiya Chen 

Study leader：

Zhengbo Song 

申请注册联系人电话：

Applicant telephone：

 +86 156 1831 0761

研究负责人电话：

Study leader's
telephone：

+86 138 5715 3345

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：

 chenshiya@genhousebio.com

研究负责人电子邮件：

Study leader's E-mail：

 songzb@zjcc.org.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：

中国（江苏）自由贸易试验区苏州片区苏州工业园区新泽路1号生物医药产业园三期A区8号楼401单元

研究负责人通讯地址：

杭州市拱墅区半山东路1号

Applicant address：

Unit 401, Building 8, Zone A, Phase III, Bio-Pharmaceutical Industrial Park, No. 1, Xinze Road, Suzh

Study leader's address：

No. 1, East Banshan Road, Gongshu District, Hangzhou , P.R. China 310022

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：

勤浩医药（苏州）有限公司

Applicant's institution：

Suzhou Genhouse Bio Co., Ltd

研究负责人所在单位：

浙江省肿瘤医院

Affiliation of the Leader：

Zhejiang Cancer 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：

 IRB-2024-96号（注）

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：

浙江省肿瘤医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Zhejiang Cancer Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-01-15 00:00:00

伦理委员会联系人：

王丽虹

Contact Name of the ethic committee：

Wang LiHong

伦理委员会联系地址：

杭州市拱墅区半山东路1号

Contact Address of the ethic committee：

No. 1, East Banshan Road, Gongshu District, Hangzhou , P.R. China 310022

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 571 8812 2564

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 ec@zjcc.org.cn

研究实施负责（组长）单位：

浙江省肿瘤医院

Primary sponsor：

Zhejiang Cancer Hospital

研究实施负责（组长）单位地址：

杭州市拱墅区半山东路1号

Primary sponsor's address：

No. 1, East Banshan Road, Gongshu District, Hangzhou , P.R. China 310022

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)：

Country：

China

Province：

Zhejiang

City：

单位(医院)：

浙江省肿瘤医院

具体地址：

杭州市拱墅区半山东路1号

Institution
hospital：

Zhejiang Cancer Hospital

Address：

No. 1, East Banshan Road, Gongshu District, Hangzhou , P.R. China 310022

经费或物资来源：

勤浩医药（苏州）有限公司

Source(s) of funding：

Suzhou Genhouse Bio Co., Ltd

研究疾病：

复发或转移性晚期恶性实体瘤  

Target disease：

Recurrent or metastatic advanced malignant tumors

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期临床试验 

Study phase：

1

研究设计：

单臂 

Study design：

Single arm 

研究目的：

剂量递增研究（Ia） 主要目的 1.评估GH2616片在晚期实体瘤中的安全性、耐受性和剂量限制性毒性（DLTs）。 2.确定GH2616片治疗晚期实体瘤的最大耐受剂量（MTD）和/或扩展期推荐剂量（RDEs）。 次要目的 1.评估GH2616片单次给药和多次给药在晚期实体瘤中的药代动力学（PK）特征。 2.评估GH2616片在晚期实体瘤中的初步抗肿瘤活性。 剂量扩展研究（Ib） 主要目的 1.评估GH2616片在具有TP53突变和WGD特征的晚期实体瘤受试者中的初步抗肿瘤活性和安全性。 2.确定GH2616片II期临床研究推荐剂量（RP2D）。 次要目的 1.评估GH2616片在具有TP53突变和WGD特征的晚期实体瘤受试者中的PK特征。  

Objectives of Study：

Dose Escalation Study (Ia) Primary purpose 1.To evaluate the safety, tolerability, and dose-limiting toxicities (DLTs) of GH2616 tablets in advanced solid tumors. 2.To determine the maximum tolerated dose (MTD) and/or recommended dose (RDEs) for the expansion phase of GH2616 tablets for the treatment of advanced solid tumors. Secondary purpose 2.To evaluate the pharmacokinetic (PK) profile of GH2616 tablets in advanced solid tumors as a single dose and multiple doses. 2.To evaluate the preliminary antitumor activity of GH2616 tablets in advanced solid tumors. Dose Expansion Study (Ib) Primary purpose 1.To evaluate the preliminary anti-tumor activity and safety of GH2616 tablets in subjects with advanced solid tumors with TP53 mutations and WGD characteristics. 2.Determine the recommended dose (RP2D) for the phase II clinical study of GH2616 tablets. Secondary purpose 1.To evaluate the PK profile of GH2616 tablets in subjects with advanced solid tumors with TP53 mutations and WGD features.

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. 年龄≥18岁的男性或女性。 2. 经研究者评估以下二点并认为适合参与本研究：a.受试者充分理解本研究的要求并自愿签署书面知情同意书；b.能够遵守本研究的用药要求以及所有与研究相关的程序和评估。 3. 符合以下条件的肿瘤类型： Ia期： 经组织学或细胞学确诊的标准治疗失败或不耐受或无标准治疗的复发或转移性晚期恶性实体瘤受试者，包括但不限于高级别浆液性卵巢癌（HGSOC），子宫癌肉瘤（UCS），非小细胞肺癌（NSCLC），小细胞肺癌（SCLC），三阴性乳腺癌（TNBC），尿路上皮癌（BLCA），结直肠癌（CRC）等。 Ib期： 经组织学或细胞学确诊且经实验室证实具有TP53基因突变和基因组加倍（WGD）特征的复发或转移性晚期恶性实体瘤受试者，包括但不限于高级别浆液性卵巢癌（HGSOC），子宫癌肉瘤（UCS），非小细胞肺癌（NSCLC），小细胞肺癌（SCLC），三阴性乳腺癌（TNBC），尿路上皮癌（BLCA），结直肠癌（CRC）等。各瘤种具体要求如下： 1）高级别浆液性卵巢癌：至少经过一线及以上含铂类化疗后进展/复发的铂耐药卵巢癌或至少经过二线及以上含铂类化疗后进展/复发的铂敏感卵巢癌。“铂耐药”的定义为：发现肿瘤复发时间与既往含铂方案末次化疗时间之间的间隔＜6个月或者肿瘤在初始治疗或者复发治疗过程中进展。“铂敏感”的定义为发现肿瘤复发时间与既往末次化疗时间之间的间隔≥6个月。应从最后一次铂类药物治疗之日起至疾病进展之日止计算间隔时间。 2）子宫癌肉瘤：至少经过一线及以上含铂化疗后进展/复发。 3)非小细胞肺癌：至少经含铂方案治疗后进展或复发，已知阳性基因驱动如表皮生长因子受体（EGFR）敏感突变/间变性淋巴瘤激酶（ALK）融合/c-ros癌基因1（ROS1）融合基因等需经过标准靶向治疗后进展或复发。 4）小细胞肺癌：至少经含铂方案治疗后进展或复发。 5）三阴性乳腺癌：至少经过一线化疗后进展/复发。 6）尿路上皮癌：至少经过一线及以上标准治疗后进展/复发。 7）结直肠癌：至少经过二线及以上标准治疗后进展/复发。 注：辅助治疗的受试者治疗结束后小于6个月出现疾病进展，可认为是经一线治疗； 4. 预期生存时间≥12周。 5. 美国东部肿瘤协作组（ECOG）体力状况评分（附录 1：美国东部肿瘤协作组（ECOG）体力状态量表）0或1分； 6. 根据实体瘤疗效评价标准（RECIST）1.1（附录 2：实体瘤疗效评价治疗（RECIST 1.1）），至少有1个可测量病灶。 7. 受试者在筛选时具备足够的重要脏器功能（要求筛查前14天内未曾输血、未使用造血刺激因子或人体白蛋白制剂），具体定义如下： a) 血常规：绝对中性粒细胞计数（ANC）≥1.5 × 109/L；血小板计数（PLT）≥100 × 109/L；血红蛋白（HGB）≥90 g/L（9 g/dL）； b) 肝功能：血清总胆红素（TBIL）≤1.5 ×正常值上限（ULN），肝转移或者已证实患有Gilbert综合征的受试者，TBIL≤3 × ULN。对于无肝转移的受试者，丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）≤2.5 × ULN，肝转移的受试者，ALT或AST≤5 × ULN； c) 肾功能：根据Cockcroft-Gault方法（附录 3：肌酐清除率计算公式）计算的肌酐清除率（CLCr）≥60 mL/min； d) 凝血功能：活化部分凝血活酶时间（APTT）和国际标准化比率（INR）≤1.5 × ULN（接受抗凝治疗的受试者指标在治疗范围内）； e) 心功能标准：超声心动图（ECHO）显示左室射血分数大于50%。 8. 育龄期女性受试者在首次使用试验药物前7天内的血妊娠试验必须为阴性；有生育能力的合格受试者（男性和女性）必须同意在试验期间和末次用药后至少3个月内与其伴侣一起使用可靠的避孕方法（激素或屏障法或禁欲等）。有生育能力的受试者定义为性成熟并且有生物学潜在生育能力。

Inclusion criteria

1. Male or female aged 18 years or older. 2. The researchers assessed the following two points and considered it suitable to participate in this study: a. The subjects fully understood the requirements of this study and voluntarily signed a written informed consent; b. Be able to comply with the medication requirements of the study and all procedures and evaluations related to the study. 3. Tumor types that meet the following criteria: Stage Ia: Subjects with recurrent or metastatic advanced malignant tumors diagnosed histologically or cytologically with standard treatment failure or intolerance or no standard treatment, including but not limited to high-grade serous ovarian cancer (HGSOC), uterine carcinosarcoma (UCS), non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), triple negative breast cancer (TNBC), Urothelial carcinoma (BLCA), colorectal cancer (CRC), etc. Stage Ib: Subjects with histologically or cytologically confirmed, laboratory-confirmed recurrent or metastatic advanced malignant tumors with TP53 gene mutation and genomic doubling (WGD) features, including but not limited to high-grade serous ovarian cancer (HGSOC), uterine carcinosarcoma (UCS), non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), Triple negative breast cancer (TNBC), urothelial carcinoma (BLCA), colorectal cancer (CRC), etc. The specific requirements for each tumor type are as follows: 1) High-grade serous ovarian cancer: platinum-resistant ovarian cancer that has progressed/recurred after at least first-line and more platinum-containing chemotherapy, or platinum-sensitive ovarian cancer that has progressed/recurred after at least second-line and more platinum-containing chemotherapy. "Platinum-resistant" was defined as < 6 months between the time of discovery of tumor recurrence and the time of the last chemotherapy of the previous platinum-containing regimen or tumor progression during initial or recurrent therapy. "Platinum-sensitive" was defined as the interval of >=6 months between the time of discovery of tumor recurrence and the time of the last prior chemotherapy. The interval should be calculated from the date of the last platinum drug treatment to the date of disease progression. 2) Uterine carcinosarcoma: Progression/recurrence after at least first-line and more platinum-containing chemotherapy. 3) Non-small cell lung cancer: progression or recurrence after treatment with at least a platinum-containing regimen, and known positive gene drivers such as epidermal growth factor receptor (EGFR) sensitive mutation/anergic lymphoma kinase (ALK) fusion /c-ros oncogene-1 (ROS1) fusion gene require progression or recurrence after standard targeted therapy. 4) Small cell lung cancer: Progression or recurrence after treatment with at least a platinum-containing regimen. 5) Triple-negative breast cancer: progression/recurrence after at least first-line chemotherapy. 6) Urothelial carcinoma: Progression/recurrence after at least first-line and above standard treatment. 7) Colorectal cancer: progression/recurrence after at least second-line and above standard treatment. Note: Participants with adjuvant therapy who developed disease progression less than 6 months after the end of treatment could be considered to have received first-line treatment; 4. Expected survival >=12 weeks. 5. ECOG Physical status Score (Appendix 1: ECOG Physical Status Scale) 0 or 1; 6. Have at least one measurable lesion according to RECIST 1.1 (Appendix 2: RECIST 1.1). 7. The subjects had sufficient vital organ function at the time of screening (no blood transfusion, hematopoietic stimulating factors or human albumin preparations were required within 14 days prior to screening), which was defined as follows: a) Blood routine: absolute neutrophil count (ANC) >=1.5 × 10^9/L; Platelet count (PLT) >=100 × 10^9/L; Hemoglobin (HGB) >=90 g/L (9 g/dL); b) Liver function: Serum total bilirubin (TBIL) <=1.5 × upper limit of normal (ULN), subjects with liver metastasis or confirmed Gilbert syndrome, TBIL<=3 × ULN. For subjects without liver metastasis, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=2.5 × ULN; for subjects with liver metastasis, ALT or AST<=5 × ULN; c) Renal function: creatinine clearance (CLCr) >=60 mL/min as calculated by the Cockcroft-Gault method (Appendix 3: Creatinine clearance formula); d) Coagulation function: Activated partial thromboplastin time (APTT) and international standardized ratio (INR) <=1.5 × ULN (the index of subjects receiving anticoagulation therapy is within the treatment range); e) Cardiac function criteria: Echocardiography (ECHO) showed left ventricular ejection fraction greater than 50%. 8. The blood pregnancy test of female subjects of reproductive age within 7 days prior to the first use of the test drug must be negative; Eligible subjects (male and female) who are fertile must agree to use a reliable contraceptive method (hormonal or barrier method or abstinence, etc.) with their partner during the trial and for at least 3 months after the last dose. Fertile subjects are defined as sexually mature and biologically fertile.

排除标准：

1. GH2616片首次给药前21天内接受过化疗，或前28天内接受过放疗、生物治疗、内分泌治疗、靶向治疗、免疫治疗等抗肿瘤药物治疗，此外，对以下抗肿瘤药物或治疗做特别规定：1）亚硝基脲或丝裂霉素C为首次使用研究药物前6周内；2）口服氟尿嘧啶类、小分子靶向药物以及有抗肿瘤适应症的中药为首次使用研究药物前14天内；3）局部姑息性放射治疗为首次使用研究药物前14天内。 2. 首次给药前28天内接受过其它未上市的临床研究药物或治疗。 3. 在GH2616片首次给药之前28天存在既往抗肿瘤治疗引起的急性毒性未恢复至美国国立癌症研究所不良事件通用术语标准（NCI CTCAE）5.0版本≤1级或入组标准规定的基线水平（脱发、乏力等研究者判断无安全风险的毒性除外）。 4. 静息状态12导联心电图（ECG）检查平均校正QT间期（QTc，采用Fridericia’s校正公式）> 470 ms（如有临床指征，可增加心电图检测频次）。各种有临床意义的心律、传导、静息ECG形态异常，例如完全性左束支传导阻滞，III度传导阻滞，II度传导阻滞，PR间期> 250 ms。可能增加QTc延长风险或心律失常事件风险的各种因素，例如心力衰竭，低钾血症，先天性长QT综合征，家族史中直系亲属有长QT综合征或不到40岁就不明原因猝死，正在使用任何已知QT间期延长的药物。 5. 存在持续或活动性感染，包括： a) 活动性乙型肝炎（乙肝表面抗原（HbsAg）阳性且乙型肝炎病毒脱氧核糖核酸（HBV-DNA）＞500 IU/ml或1000 cps/ml或研究中心检测下限[仅当研究中心检测下限高于500 IU/ml或1000 cps/ml时]），允许除干扰素以外的抗病毒治疗；活动性丙型肝炎（丙型肝炎病毒（HCV）抗体阳性但丙型肝炎病毒核糖核酸（HCV-RNA）<研究中心检测下限的受试者允许纳入）； b) HIV感染者（HIV 1/2抗体阳性）； c) 已知的梅毒活动性感染。 6. 症状性或活动性进展的中枢神经系统（CNS）转移。 只有满足以下所有标准，有CNS病灶且经过治疗或未经治疗的无症状受试者才符合资格： a) 存在根据RECIST 1.1确定的CNS之外的可测量病灶。 b) 受试者无颅内出血或脊髓出血史。 c) 受试者在开始研究治疗前28天内未进行立体定向放射治疗全脑放射治疗，未进行神经外科切除术。 d) 受试者在CNS疾病治疗时未持续使用皮质类固醇。 e) 转移限于小脑或幕上区（即，没有转移至中脑、脑桥、髓质或脊髓）。 f) 没有证据表明在完成CNS定向治疗（若给予）和开始研究治疗之间存在中期进展。 7. 未能控制的并发疾病，如： a)开始研究治疗前28天内发生严重感染，包括但不限于因感染、菌血症或重症肺炎并发症而住院治疗；或开始研究治疗前两周内接受过治疗性口服或静脉注射抗生素。因穿刺活检使用预防性抗生素的受试者可入组； b) 开始研究治疗前6个月内符合纽约心脏病协会心功能分级>=II级的心力衰竭； c) 开始治疗前5年内或同时患有其它恶性肿瘤（根治性治疗且无疾病复发证据的非黑色素瘤的皮肤基底细胞癌或鳞状细胞癌、乳腺/宫颈原位癌、浅表膀胱癌等原位癌除外）； d) 当前或既往有癌性脑膜炎、脊髓压迫等情况的受试者； e) 开始研究治疗前28天内出现未受控制的高血压，定义为即使在接受多种降压药治疗的情况下收缩压>= 160 mmHg 或者舒张压>=100 mmHg； f) 开始研究治疗前6个月内发生过任何动脉血栓栓塞事件，包括心肌梗死、不稳定型心绞痛、脑血管意外或一过性脑缺血发作； g) 显著的营养不良，如需要静脉补充营养液。在首剂研究药物给药之前营养不良纠正后稳定28天以上者可以入组； h) 肿瘤侵犯周围重要脏器或血管（如纵膈大血管、上腔静脉、气管、食管等），或存在发生食管气管瘘或食管胸膜瘘风险； i) 食管或气管腔内支架植入术后； j) 开始研究治疗前6个月内有胃肠道穿孔和/或瘘管的病史； k) 未得到控制的胸腔积液、心包积液或需要反复引流的腹水（每月一次或更频繁）； l) 未得到控制的肿瘤相关疼痛，或无稳定的疼痛治疗方案。 8. 对GH2616片或其制剂组分过敏。 9. 对口服药物吸收有显著影响，如不能吞咽、慢性泄泻和肠梗阻等。 10. 受试者具有严重性基础肺部疾病或病史，如中重度慢性阻塞性肺病，肺间质疾病病史，药物诱导性肺间质疾病，急性或慢性感染性肺炎、肺移植等。 11. 首次给药前14天内或5个半衰期内（以较长者为准）使用P-糖蛋白（P-gp）强抑制剂和强诱导剂（附录 6）。 12. 妊娠或哺乳期妇女。 13. 已知异体器官移植史和异体造血干细胞移植史。 14. 首次给药前28天之内接受过重大的外科手术（开颅、开胸、开腹手术、血管介入手术），或者存在未愈合的伤口、溃疡或骨折。注：以姑息治疗为目的，对于孤立病灶的局部手术治疗是可以接受的。 15. 既往有明确的精神障碍史并服用药物进行治疗者。 16. 既往接受过KIF18A抑制剂治疗。 17. 具有POLE热点突变，dMMR/MSI-H，或可识别的超突变表型。 18. 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. GH2616 tablets were treated with chemotherapy within 21 days before the first administration, or with anti-tumor agents such as radiotherapy, biotherapy, endocrine therapy, targeted therapy, and immunotherapy within 28 days before the first administration. In addition, special provisions are made for the following anti-tumor drugs or therapies: 1) nitrosourea or mitomycin C is treated within 6 weeks before the first administration of the investigational drug; 2) Oral fluorouracil, small molecule targeted drugs and Chinese medicines with anti-tumor indications within 14 days before the first use of the study drug; 3) Local palliative radiotherapy was prescribed within 14 days prior to the first use of the study drug. 2. Received other investigational drugs or treatments that are not on the market within 28 days prior to initial dosing. 3. In the 28 days prior to the first administration of GH2616 tablets, acute toxicity due to previous antitumor therapy did not return to the baseline level specified by the National Cancer Institute General Terminology Standard for Adverse Events (NCI CTCAE) version 5.0 <= Grade 1 or inclusion criteria (except for toxicity such as alopecia and fatigue that the investigators determined had no safety risk). 4. The mean corrected QT interval (QTc, using Fridericia's correction formula) for resting 12-lead electrocardiogram (ECG) tests was > 470 ms (increased ECG frequency if clinically indicated). A variety of clinically significant cardiac rhythm, conduction, and resting ECG morphological abnormalities, such as complete left bundle branch block, degree III block, degree II block, and PR interval > 250 ms. Various factors that may increase the risk of prolonged QTc or arrhythmia events, such as heart failure, hypokalemia, congenital long QT syndrome, immediate family history of long QT syndrome or sudden unexplained death before the age of 40, are taking any medications with known prolonged QT interval. 5. There is persistent or active infection, including: a) Active hepatitis B (hepatitis B surface antigen (HbsAg) positive with hepatitis B virus deRNA (HBV-DNA) > 500 IU/ml or 1000 cps/ml or lower limit of study center detection [only when lower limit of study center detection is higher than 500 IU/ml or 1000 cps/ml]), Allow antiviral therapy other than interferon; Active hepatitis C (subjects who are positive for hepatitis C virus (HCV) antibodies but have hepatitis C virus ribonucleic acid (HCV-RNA) < the lower limit of the study center detection are allowed to be included); b) HIV infected persons (HIV 1/2 antibody positive); c) Known active syphilis infection. 6. Central nervous system (CNS) metastases with symptomatic or active progression. Asymptomatic subjects with CNS lesions, treated or untreated, are eligible only if they meet all of the following criteria: a) The presence of measurable lesions outside the CNS as determined by RECIST 1.1. b) Subjects had no history of intracranial or spinal bleeding. c) Subjects did not undergo stereotactic radiation therapy whole brain radiation therapy and did not undergo neurosurgical resection within 28 days prior to initiation of study therapy. d) The subject did not use corticosteroids continuously during treatment for CNS disease. e) Metastasis is limited to the cerebellum or supratentorial area (i.e., no metastasis to the midbrain, pons, medulla, or spinal cord). f) There is no evidence of intermediate progress between completion of CNS targeted therapy (if given) and initiation of investigational therapy. 7. Uncontrolled co-morbiditions, such as: a) serious infections occurring within 28 days prior to the start of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia; Or received therapeutic oral or intravenous antibiotics within two weeks before starting the study. Subjects receiving prophylactic antibiotics for puncture biopsy could be enrolled; b) heart failure meeting the New York Heart Association Heart Function Scale >=II within 6 months prior to initiation of study treatment; c) have other malignancies within 5 years prior to the start of treatment or at the same time (except for non-melanoma skin basal cell carcinoma or squamous cell carcinoma, carcinoma in situ of the breast/cervix, superficial bladder carcinoma and other carcinoma in situ with radical treatment and no evidence of disease recurrence); d) Subjects with current or past conditions such as cancerous meningitis or spinal cord compression; e) Uncontrolled hypertension within 28 days prior to study initiation, defined as systolic blood pressure >= 160 mmHg or diastolic blood pressure >=100 mmHg, even when treated with multiple antihypertensive agents; f) any arterial thromboembolic event, including myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack, occurred within 6 months prior to initiation of study treatment; g) Significant malnutrition, such as the need for intravenous nutritional solutions. Patients with stable malnutrition for more than 28 days after correction before the first dose of the study drug could be enrolled; h) Tumor invasion of surrounding important organs or blood vessels (such as mediastinal vasa, superior vena cava, trachea, esophagus, etc.), or esophagotracheal fistula or esophagopleural fistula risk; i) after stent implantation in esophagus or trachea; j) A history of gastrointestinal perforation and/or fistula within 6 months prior to initiation of study treatment; k) uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once a month or more frequently); l) uncontrolled tumor-related pain, or no stable pain treatment options. 8. Allergic to GH2616 tablets or its formulation components. 9. It has significant effects on oral drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction. 10. Subjects have a history of severe underlying lung disease, such as moderate to severe chronic obstructive pulmonary disease, history of pulmonary interstitial disease, drug-induced pulmonary interstitial disease, acute or chronic infectious pneumonia, lung transplantation, etc. 11. Use of P-glycoprotein (P-gp) suppressors and strong inducers within 14 days prior to first administration or within 5 half-lives, whichever is older (Appendix 6). 12. Pregnant or lactating women. 13. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. 14. Major surgical procedures (craniotomy, thoracotomy, laparotomy, vascular intervention) or unhealed wounds, ulcers, or fractures were performed within 28 days prior to the first dose. Note: For palliative care purposes, local surgical treatment of isolated lesions is acceptable. 15. People who have a clear history of mental disorders and take medication for treatment. 16. Previously received KIF18A inhibitor treatment. 17. Have a POLE hotspot mutation, dMMR/MSI-H, or a recognizable hypermutant phenotype. 18. The investigator believes that the subjects are not suitable to participate in this clinical study for other reasons.

研究实施时间：

Study execute time：

从 From 2023-12-01 00:00:00至 To 2026-09-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-03-13 00:00:00 至 To 2025-11-30 00:00:00

干预措施：

Interventions：

组别：

Ia期：剂量递增阶段

样本量：

 66

Group：

Phase Ia: Dose escalation stage

Sample size：

干预措施：

Gh2616片口服治疗

干预措施代码：

Intervention：

Gh2616 tablets for oral therapy

Intervention code：

组别：

Ib期：剂量扩展研究

样本量：

 90

Group：

Phase Ib: Dose Expansion Study

Sample size：

干预措施：

Gh2616片口服治疗

干预措施代码：

Intervention：

Gh2616 tablets for oral therapy

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

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：

 三级甲等 

Institution
hospital：

Zhejiang Cancer Hospital

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 河南 

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)：

 湖北 

市(区县)：

  

Country：

China

Province：

Hubei

City：

单位(医院)：

 湖北省肿瘤医院 

单位级别：

 三级甲等 

Institution
hospital：

Hubei Cancer Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

抗肿瘤活性评价指标

指标类型：

次要指标

Outcome：

Evaluation indicators for anti-tumor activity

Type：

Secondary indicator

测量时间点：

在入组前28天内进行肿瘤评估，C1D1开始每6w±7d进行一次影像学检查和肿瘤评估，直至试验终止。

测量方法：

包括颈部、胸部、腹部、盆腔、脑部的CT或MRI，如受试者有骨转移或临床指征，增加骨扫描

Measure time point of outcome：

Tumor evaluation was performed within 28 days prior to enrollment, with imaging and tumor evaluation

Measure method：

CT or MRI of the neck, chest, abdomen, pelvis, and brain are included, and bone scans are added if the subject has bone metastases or is clinically indicated

指标中文名：

GH2616 片在晚期实体瘤中的安全性、耐受性和剂量限制性毒性（DLTs）

指标类型：

主要指标

Outcome：

Safety, tolerability, and dose limiting toxicity (DLTs) of GH2616 tablets in advanced solid tumors

Type：

Primary indicator

测量时间点：

筛选期、治疗期C1D1、C1D8、C1D15、C2D1、C2D15、C3D1、CnD1、EOT 安全性随访

测量方法：

生命体征；12导联心电图；实验室检查（血常规、血生化、凝血功能、尿常规）；? 不良事件实验室检查项目：血常规 红细胞计数、白细胞计数、中性粒细胞绝对数、淋巴细胞绝对数、单核细胞绝对数、嗜酸性粒细胞绝对数、嗜碱性粒细胞绝对数、血红蛋白、血小板计数、红细胞比容凝血功能 凝血酶原时间、活化部分凝血活酶时间、凝血酶时间、纤维蛋白原、国际标准化比率血生化：

Measure time point of outcome：

The observation period for DLT was 28 days after the first dose (single dose and multiple consecutiv

Measure method：

Vital signs; 12 lead electrocardiogram; Laboratory tests (blood routine, blood biochemistry, coagulation function, urine routine); Adverse events Laboratory inspection items: Blood routine includes red blood cell count, white blood cell count, absolute neutrophil count, absolute lymphocyte count, absolute monocyte count, absolute eosinophil count, absolute basophil count, hemoglobin, platelet count, and hematocrit Coagulation function prothrombin time, activated partial thromboplastin time, thro

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

药代动力学样本

组织：

Sample Name：

Pharmacokinetic samples

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：

药效动力学样本

组织：

Sample Name：

Pharmacodynamic samples

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：

基因突变及基因组加倍肿瘤组织样本

组织：

Sample Name：

Gene mutations and genome duplication in tumor tissue samples

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：

基因突变及基因组加倍肿瘤全血样本

组织：

Sample Name：

Gene mutations and genome duplication in tumor whole blood samples

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)：

None

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：

无

Blinding：

None

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）：

国家生物信息中心 https://ngdc.cncb.ac.cn/gsub/

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

China National center for Bioinformation (https://ngdc.cncb.ac.cn/gsub/)

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：

EDC采集数据

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

EDC

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2025-05-29 09:38:16