ChiCTR2600126983 版本V1.0 版本创建时间2026/06/22 14:28:58 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：

ChiCTR2600126983 

最近更新日期：

Date of Last Refreshed on：

2026-06-22 14:27:05 

注册时间：

Date of Registration：

2026-06-22 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

评价GTA182联合伏美替尼在MTAP纯合型缺失的局部晚期或转移性非小细胞肺癌（NSCLC）受试者中的安全性、耐受性、药代动力学以及初步有效性的剂量递增和剂量扩展的I期临床研究

Public title：

An I-phase clinical study evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of GTA182 combined with volmetinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with MTAP homozygous deletion

注册题目简写：

English Acronym：

研究课题的正式科学名称：

评价GTA182联合伏美替尼在MTAP纯合型缺失的局部晚期或转移性非小细胞肺癌（NSCLC）受试者中的安全性、耐受性、药代动力学以及初步有效性的剂量递增和剂量扩展的I期临床研究

Scientific title：

An I-phase clinical study evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of GTA182 combined with volmetinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with MTAP homozygous deletion

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：

陆舜 

研究负责人：

陆舜 

Applicant：

LUSHUN 

Study leader：

SHUN LU 

申请注册联系人电话：

Applicant telephone：

+86 21 62821990

研究负责人电话：

Study leader's telephone：

+86 21 62821990

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

shun_lu@hotmail.com

研究负责人电子邮件：

Study leader's E-mail：

yaxianyao@sina.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：

上海市徐汇区淮海西路241号

研究负责人通讯地址：

上海市徐汇区淮海西路241号

Applicant address：

241 Huaihai West Road, Xuhui District, Shanghai

Study leader's address：

No. 241 Huaihai West Road, Xuhui District, Shanghai

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

上海市胸科医院

Applicant's institution：

Shanghai Chest Hospital

研究负责人所在单位：

上海市胸科医院

Affiliation of the Leader：

Shanghai Chest?Hospital

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

LS25113

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

上海市胸科医院伦理委员会

Name of the ethic committee：

Ehtics Committee of Shanghai Chest Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2025-09-30 00:00:00

伦理委员会联系人：

陈仲林

Contact Name of the ethic committee：

Chen Zhonglin

伦理委员会联系地址：

上海市徐汇区淮海西路241号

Contact Address of the ethic committee：

No. 241 Huaihai West Road, Xuhui District, Shanghai

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 21 22200000

伦理委员会联系人邮箱：

Contact email of the ethic committee：

chestgcp@126.com

研究实施负责（组长）单位：

上海市胸科医院

Primary sponsor：

Shanghai Chest?Hospital

研究实施负责（组长）单位地址：

上海市徐汇区淮海西路241号

Primary sponsor's address：

No. 241 Huaihai West Road, Xuhui District, Shanghai

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

上海市

市(区县)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

上海市胸科医院

具体地址：

上海市徐汇区淮海西路241号

Institution
hospital：

Shanghai Chest Hospital

Address：

No. 241 Huaihai West Road, Xuhui District, Shanghai

经费或物资来源：

上海湃隆生物科技有限公司

Source(s) of funding：

Shanghai Pailong Biotechnology Co., Ltd

Target disease：

MTAP homozygous deletion in locally advanced or metastatic NSCLC.

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：

主要目的： 评估GTA182 联合伏美替尼在MTAP 纯合型缺失局部晚期或转移性NSCLC受试者中的安全性和耐受性，以确定扩展期推荐的联合剂量。 次要目的： 描述GTA182 联合伏美替尼在MTAP 纯合型缺失局部晚期或转移性NSCLC受试者中的药代动力学特征； 评估GTA182 联合伏美替尼在MTAP 纯合型缺失局部晚期或转移性NSCLC受试者中的初步有效性。 探索性目的： 探索与GTA182 疗效相关的生物标志物。 Ib 期（剂量扩展阶段） 主要目的： 评估在Ia 期推荐的联合剂量下GTA182 联合伏美替尼在MTAP 纯合型缺失局部晚期或转移性NSCLC 受试者中的安全性和耐受性，以确认联合用药RP2D。 次要目的： 评估在Ia 期推荐的联合剂量下GTA182 联合伏美替尼在MTAP 纯合型缺失局部晚期或转移性NSCLC 受试者中的药代动力学特征； 评估在Ia 期推荐的联合剂量下GTA182 联合伏美替尼在MTAP 纯合型缺失局部晚期或转移性NSCLC 受试者中的初步有效性，为后续临床试验推荐剂量选择提供依据。 探索性目的： 探索与GTA182 疗效相关的生物标志物。  

Objectives of Study：

Main objective: To evaluate the safety and tolerability of GTA182 combined with vorasetinib in patients with MTAP homozygous deletion in locally advanced or metastatic NSCLC, and to determine the recommended combined dose for the extension phase. Secondary objective: To describe the pharmacokinetic characteristics of GTA182 combined with vorasetinib in patients with MTAP homozygous deletion in locally advanced or metastatic NSCLC; To assess the initial efficacy of GTA182 combined with vorasetinib in patients with MTAP homozygous deletion in locally advanced or metastatic NSCLC. Exploratory objective: To explore the biomarkers related to the efficacy of GTA182. Ib phase (dose expansion phase) Main objective: To evaluate the safety and tolerability of GTA182 combined with vorasetinib at the recommended combined dose from the Ib phase in patients with MTAP homozygous deletion in locally advanced or metastatic NSCLC, and to confirm the recommended phase 2 dose (RP2D) of the combination therapy. Secondary Objectives: To evaluate the pharmacokinetic (PK) profile of GTA182 in combination with furmonertinib in patients with locally advanced or metastatic NSCLC harboring homozygous MTAP deletion at the recommended combination dose from the Phase Ia study; To evaluate the preliminary efficacy of GTA182 in combination with furmonertinib in patients with locally advanced or metastatic NSCLC harboring homozygous MTAP deletion at the recommended combination dose from the Phase Ia study, providing a basis for dose selection in subsequent clinical trials. Exploratory objective: To explore the biomarkers related to the efficacy of GTA182.

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. 受试者须在试验前对本研究知情同意，并自愿签署书面的ICF，同意遵守研究方案； 2. 签署ICF 时，≥18 周岁男性或女性受试者； 3. 预期寿命>3 个月； 4. 美国东部肿瘤协作组（ECOG）体力状态评分0 或1； 5. 能够提供存档的和/或基线期的肿瘤组织样本，以满足中心实验室MTAP 纯合型 缺失检测的最低组织要求或能够提供研究者认可的既往NGS 或免疫组化（IHC）证实为 MTAP 纯合型缺失的检测报告； 6. 经组织学或细胞学确诊的局部晚期或转移性NSCLC； 7. 既往治疗史需满足以下要求：既往一代、二代、三代EGFR-TKIs 治疗失败，或 一代、二代EGFR-TKIs 治疗失败且EGFR T790M 阴性； 8. 根据RECIST V1.1 标准，至少有1 个可测量的病灶； 9. 首次给药前7 天内根据以下实验室检查，判断受试者具有良好的骨髓功能、心、 肺、肝、肾功能和凝血功能（研究药物首次给药前14 天不允许输血或给予其他生长因 子的支持治疗）：?骨髓功能：ANC≥1.5×10^9/L，血小板计数≥100×10^9/L 和血红蛋白≥90g/L；?肝脏：总胆红素（TBIL）≤1.5×ULN，或TBIL≤3×ULN（如有Gilbert’s disease）； AST 和ALT≤2.5×ULN（如伴肝转移，则≤5×ULN）；血清白蛋白（ALB）≥ 30g/L； ?肾脏：血清肌酸酐浓度<1.5×ULN；如果血清肌酸酐浓度≥1.5×ULN，则估计肌 酸酐清除率必须 ≥ 50 mL/min（根据Cockroft-Gault 公式）；?凝血（未接受抗凝治疗）：活化部分凝血活酶时间（APTT）≤1.5×ULN；凝血酶原时间（PT）或国际标准化比值（INR）≤1.5×ULN。接受抗凝药物治疗者必须有INR和/或APTT≤预期使用的治疗范围上限； 10. 具有生育能力的男性和育龄期女性必须同意从签署ICF 开始直至试验药物末次给药后180 天期间采取可靠的避孕措施。育龄期女性在首次试验药物给药前≤7 天内的血妊娠检测结果必须为阴性；注：非育龄期女性包括永久绝育（子宫切除术、双侧卵巢切除术或双侧输卵管切除术）和已绝经。对于≥60 岁女性，如果在计划入组日期前12 个月已停经且无其他医学病因，则认为该名女性已绝经。对于<60 岁的女性，如果停止外源性激素治疗后已停经12 个月或以上、且促卵泡生成激素（FSH）水平在绝经后范围内，则认为该名女性已绝 经。 11. 距首次给予试验药物前的抗肿瘤治疗方案应有充分的治疗洗脱期，定义如下：治疗 洗脱期大手术 ≥ 4 周放射治疗 ≥ 4 周（如放射治疗为不涉及肺腹盆的姑息立体定向放疗，则≥ 2 周）放射性粒子治疗 ≥ 3 个月核素治疗 ≥ 3 个月自体移植（包括CAR-T 及其他同类治疗）≥ 3 个月激素治疗 ≥ 2 周或由研究者判断化疗 ≥ 2 周（系统性化疗）； ≥ 6 周（亚硝基脲或丝裂霉素C）；靶向治疗 ≥ 1 周（酪氨酸激酶抑制剂）；≥ 3 周（任何其他靶向药物）；≥ 4 周（靶向生物治疗）；免疫治疗 ≥ 4 周具有抗肿瘤适应症的中药/中成药 ≥ 2 周；

Inclusion criteria

1. The subjects must have given informed consent to this study before the trial and voluntarily sign the written ICF, agreeing to abide by the research protocol; 2. For male or female subjects aged 18 or above at the time of signing the ICF; 3. Expected lifespan > 3 months; 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; 5. Able to provide archived and/or baseline tumor tissue samples to meet the minimum tissue requirements for central laboratory MTAP homozygous deletion detection or able to provide a researcher-approved previous NGS or immunohistochemistry (IHC) report confirming MTAP homozygous deletion; 6. Locally advanced or metastatic NSCLC diagnosed by histological or cytological means; 7. Previous treatment history must meet the following requirements: failure of previous first-generation, second-generation, or third-generation EGFR-TKIs treatment, or failure of first-generation or second-generation EGFR-TKIs treatment and negative EGFR T790M; 8. According to the RECIST V1.1 standard, at least one measurable lesion; 9. Within 7 days before the first administration, based on the following laboratory tests, the subjects were judged to have good bone marrow function, heart, lung, liver, and kidney functions and coagulation function (the first administration of the study drug is not allowed to receive blood transfusion or other growth factor supportive treatment within 14 days): ? Bone marrow function: ANC >= 1.5×10^9/L, platelet count >= 100×10^9/L and hemoglobin >= 90g/L; ? Liver: total bilirubin (TBIL) <= 1.5×ULN, or TBIL <= 3×ULN (if Gilbert's disease exists); AST and ALT <= 2.5×ULN (if there is liver metastasis, <= 5×ULN); serum albumin (ALB) >= 30g/L; ? Kidney: serum creatinine concentration < 1.5×ULN; if serum creatinine concentration >= 1.5×ULN, the estimated creatinine clearance rate must be >= 50 mL/min (according to the Cockroft-Gault formula); ? Coagulation (without anticoagulation treatment): activated partial thromboplastin time (APTT) <= 1.5×ULN; prothrombin time (PT) or international normalized ratio (INR) <= 1.5×ULN. Patients receiving anticoagulant drug treatment must have INR and/or APTT <= the upper limit of the expected treatment range; 10. Male subjects with fertility and female subjects of childbearing age must agree to take reliable contraceptive measures from the time of signing the ICF until 180 days after the last administration of the trial drug. The blood pregnancy test result of female subjects within <= 7 days before the first administration of the trial drug must be negative; Note: Non-pregnant women include permanent sterilization (uterus removal, bilateral ovarian removal, or bilateral fallopian tube removal) and post-menopausal women. For women >= 60 years old, if they have stopped menstruation for 12 months or more before the planned enrollment date and there are no other medical causes, it is considered that the woman has reached menopause. For women < 60 years old, if they have stopped exogenous hormone treatment for 12 months or more and the follicle-stimulating hormone (FSH) level is within the post-menopausal range, it is considered that the woman has reached menopause. 11. There should be a sufficient treatment washout period between the initial administration of the investigational drug and the anti-tumor treatment regimen, as defined as follows: Major surgery >= 4 weeks Radiotherapy >= 4 weeks (if the radiotherapy is palliative stereotactic radiotherapy not involving the lungs, abdomen, or pelvis, then >= 2 weeks) Radioactive particle therapy >= 3 months Nuclear medicine therapy >= 3 months Autologous transplantation (including CAR-T and other similar treatments) >= 3 months Hormone therapy >= 2 weeks or as determined by the investigator Chemotherapy >= 2 weeks (systemic chemotherapy); >= 6 weeks (nitrogenous ureas or mitomycin C); Targeted therapy >= 1 week (tyrosine kinase inhibitors); >= 3 weeks (any other targeted drugs); >= 4 weeks (targeted biological therapy); Immunotherapy >= 4 weeks Traditional Chinese medicine / Chinese patent medicine with anti-tumor indications >= 2 weeks;

排除标准：

1. 妊娠或哺乳期女性； 2. 既往抗肿瘤治疗（包括同步放化疗或手术治疗）的毒性尚未恢复至CTCAE V5.0 等级评估≤1 级（脱发、疲乏、2 级的神经系统毒性等研究者判断无安全风险的毒性除外； 免疫治疗后出现免疫相关性甲状腺功能减退，目前正在使用甲状腺素补充（CTCAE 2 级） 的群体除外）； 3. 既往3 年内曾发生其他恶性肿瘤，但已治愈的子宫颈原位癌、皮肤鳞状细胞癌或基底细胞癌除外； 4. 既往接受过PRMT5 抑制剂和/或甲硫氨酸腺苷转移酶2A（MAT2A）抑制剂治疗； 5. 有临床意义的并发疾病，包括但不限于： ?既往6 个月内或目前患有心力衰竭或心肌梗塞、不稳定性心绞痛以及纽约心脏 协会心功能分级第II-IV 级； ?既往6 个月有高危不可控的心律失常：静息时心率>100 次/分的房性心动过速、 显著室性心律失常（如室性心动过速）或高级房室传导阻滞（如II 度房室传导阻 滞Mobitz II 型或III 度房室传导阻滞）； ?基线期存在心电图QT/QTc 间期延长者（QTcF：男性>450 ms，女性>470 ms）（男 女，QTcF 即采用Fridericia 校正公式QTcF=QT/RR^0.33 计算）； ?基线超声心动图（ECHO）显示左室射血分数（LVEF）≤50%； ?经药物治疗后仍控制不良的高血压（收缩压≥180 mmHg，舒张压≥110 mmHg）或 糖尿病（糖化血红蛋白≥9.0%）； ?既往有血管成形术、冠状动脉搭桥等心脏外科病史； ?严重主动脉瓣狭窄； ?有临床显著意义的活动性感染，需要全身抗生素、抗病毒或抗真菌治疗； ?伴有大量的浆膜腔积液，或控制不佳的浆膜腔积液者（定义为：携带引流管或引 流频率超过每周1 次） ?筛查前6 个月内发生脑卒中。基线MRI 或CT 扫描的中枢神经系统出血证据（受 试者术后无症状1 级出血稳定不足3 个月）。 ?存在药物无法控制的癫痫发作； ?首次用药前3 个月有动/静脉血栓（如下肢静脉血栓）形成，经研究者判断持续存 在且有较大安全性风险者； ?合并严重肺部疾病，包括但不限于签署知情前3 个月发生的肺栓塞、严重哮喘、 慢性阻塞性肺疾病（COPD）、限制性肺部疾病，或有活动性肺炎或间质性肺炎或 系统性类固醇治疗的肺炎，肺功能检查提示肺功能重度受损者； 6. 临床不稳定的脑转移，定义为有症状，需要类固醇、脱水药物或抗惊厥药物治疗、或需放疗以控制相关症状；存在脑膜转移，脑干转移，脊髓转移和/或压迫。经治疗后的脑转移已无症状，不需类固醇或脱水治疗，且已从前序治疗的急性毒性中恢复的受试者，根据研究者判断可被纳入研究； 7. 无法吞咽药物或患有影响药物吸收的胃肠道疾病或其它吸收不良情况，比如肠梗 阻、克罗恩病、溃疡性结肠炎、严重消化道溃疡、胃肠穿孔或急性消化道出血；或首次 服用本试验药物前有严重的胃肠道相关毒性且未恢复至2 级以下； 8. 存在活动性传染病的证据，包括梅毒（梅毒螺旋体特异性抗体与非特异性抗体均 阳性）或人类免疫缺陷病毒（HIV）阳性者，或活动性乙型肝炎者（乙肝表面抗原阳性 且乙型肝炎病毒（HBV）-DNA≥2000 IU/mL）或活动性丙型肝炎者（丙肝病毒抗体阳性 且乙型肝炎病毒（HCV）-RNA 高于参考值上限）；结核（1 年内有活动性结核感染的 证据）；如果基线时检测到HBV DNA（即高于检测上限），则需要在开始试验药物治 疗前至少7 天开始预防性抗病毒治疗且需要同意每月进行一次DNA 检测（或根据当地 乙型肝炎专家建议治疗和随访）； 9. 既往有严重过敏史或已知对试验药物辅料成分过敏； 10. 既往有明确的神经或精神障碍史，如痴呆，依从性差者； 11. 在试验药物首次给药前4 周内接种过减毒活疫苗； 12.既往有同种异体器官移植或异体外周血干细胞移植（allo-HSCT）/骨髓移植治疗 史； 13.存在有临床显著的QT 间期延长或其他心律失常或研究者认为可能增加QT 间期 延长风险的临床状态，或当前正在使用可能导致QT 间期延长/尖端扭转性室性心动过速 的药物； 14.在试验药物首次给药前7 天内使用过强效细胞色素P450 3A4（CYP3A4）抑制 剂，或在试验药物首次给药前21 天内使用过强效CYP3A4 诱导剂； 15.筛选时伴有经研究者判断可能增大安全性风险的眼部疾病； 16.研究者认为不适合参加本研究的其他原因。

Exclusion criteria：

1. Pregnant or lactating women; 2. Individuals who have experienced toxic side effects from previous anti-tumor treatments (including concurrent radiotherapy and chemotherapy or surgical treatment) and whose toxicity has not yet recovered to a CTCAE V5.0 grade assessment of <=1 (excluding hair loss, fatigue, grade 2 neurological toxicity, etc., which the investigators consider to be non-dangerous for safety; immune-related hypothyroidism that occurred after immunotherapy and is currently being treated with thyroid hormone supplementation (CTCAE grade 2)); 3. Individuals who have had other malignant tumors within the past 3 years, but have been cured (cervical carcinoma in situ, squamous cell carcinoma of the skin, or basal cell carcinoma of the skin); 4. Individuals who have received PRMT5 inhibitors and/or methionine adenosyltransferase 2A (MAT2A) inhibitors; 5. Have clinically significant concurrent diseases, including but not limited to: ? Had heart failure or myocardial infarction, unstable angina pectoris, or New York Heart Association cardiac function grade II-IV within the past 6 months or currently; ? Had high-risk and uncontrollable arrhythmias within the past 6 months: atrial tachycardia with a resting heart rate >100 beats per minute, significant ventricular arrhythmias (such as ventricular tachycardia) or advanced atrioventricular conduction block (such as second-degree atrioventricular conduction block Mobitz II or third-degree atrioventricular conduction block); ? Had baseline QT/QTc interval prolongation (QTcF: male >450 ms, female >470 ms) (for both male and female, QTcF is calculated using the Fridericia correction formula QTcF = QT/RR^0.33); ? Had baseline echocardiography (ECHO) showing left ventricular ejection fraction (LVEF) <=50%; ? Had uncontrolled hypertension (systolic blood pressure >=180 mmHg, diastolic blood pressure >=110 mmHg) or diabetes (glycated hemoglobin >=9.0%); ? Had a history of cardiac surgery, such as angioplasty or coronary artery bypass grafting; ? Had severe aortic valve stenosis; ? Had clinically significant active infections that require systemic antibiotics, antiviral or antifungal treatment; ? Had a large amount of serous cavity effusion, or poorly controlled serous cavity effusion (defined as: carrying a drainage tube or having a drainage frequency of more than once per week); ? Had evidence of central nervous system hemorrhage on baseline MRI or CT scan (stable insufficient for 3 months after postoperative asymptomatic grade 1 hemorrhage); ? Had uncontrolled seizures; ? Had thromboembolism (such as lower extremity venous thrombosis) within 3 months before the first administration, which persisted and was judged by the investigator to have a significant safety risk; ? Had severe pulmonary disease, including but not limited to pulmonary embolism, severe asthma, chronic obstructive pulmonary disease (COPD), restrictive lung disease, or active pneumonia or interstitial pneumonia or systemic steroid treatment-induced pneumonia, and had severely impaired lung function as indicated by pulmonary function tests; 6. Clinically unstable brain metastases, defined as having symptoms that require steroid, diuretic, or anticonvulsant treatment, or radiotherapy to control related symptoms; 14.having meningeal metastases, brainstem metastases, spinal cord metastases and/or compression. Subjects with asymptomatic brain metastases after treatment, who do not require steroid or diuretic treatment, and who have recovered from the acute toxicity of previous treatment, can be included in the study based on the investigator's judgment; 7. Unable to swallow drugs or have gastrointestinal diseases or other absorption disorders that affect drug absorption, such as intestinal obstruction, Crohn's disease, ulcerative colitis, severe gastrointestinal ulcers, gastrointestinal perforation or acute gastrointestinal bleeding; or had thromboembolism within 3 months before the first administration, which persisted and was judged by the investigator to have a significant safety risk; Before taking the drug in this trial, there were severe gastrointestinal-related toxicities that did not recover to grade 2 or below; 8. There is evidence of active infectious diseases, including syphilis (both specific and non-specific antibodies are positive) or human immunodeficiency virus (HIV) positive individuals, or active hepatitis B patients (positive hepatitis B surface antigen and HBV-DNA >= 2000 IU/mL) or active hepatitis C patients (positive hepatitis C virus antibody and HCV-RNA above the upper limit of the reference value); tuberculosis (evidence of active tuberculosis infection within 1 year); if HBV DNA is detected at the baseline (i.e., above the detection limit), then preventive antiviral treatment should start at least 7 days before starting the trial drug treatment and consent to conduct a DNA test once a month (or according to the local hepatitis B expert's advice for treatment and follow-up); 9. There is a history of severe allergic reactions or known allergy to the excipients of the trial drug; 10. There is a clear history of neurological or mental disorders, such as dementia, poor compliance; 11. Within 4 weeks before the first administration of the trial drug, received attenuated live vaccines; 12. Had a history of allogeneic organ transplantation or allogeneic peripheral blood stem cell transplantation/marrow transplantation treatment; 13. Have a clinically significant QT interval prolongation or other arrhythmias or a clinical condition that the investigator considers may increase the risk of QT interval prolongation, or is currently using drugs that may cause QT interval prolongation/terminally torsional ventricular tachycardia; 14. Used a strong cytochrome P450 3A4 (CYP3A4) inhibitor within 7 days before the first administration of the trial drug, or used a strong CYP3A4 inducer within 21 days before the first administration of the trial drug; 15. Had eye diseases judged by the investigator to potentially increase safety risks during screening; 16. Other reasons that the investigator considers not suitable for participating in this study.

研究实施时间：

Study execute time：

从 From 2025-09-01 00:00:00至 To 2029-04-30 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2025-11-03 00:00:00 至 To 2026-08-30 00:00:00  

干预措施：

Interventions：

组别：

Ia期

样本量：

12

Group：

Ia Group

Sample size：

干预措施：

GTA182片预设两个剂量，分别采用 3+3 设计的剂量递增原则进行研究

干预措施代码：

Intervention：

Two dose levels of GTA182 tablets were prespecified, and the dose-escalation study was conducted using the 3+3 design principle.

Intervention code：

组别：

Ib期

样本量：

20

Group：

Ib group

Sample size：

干预措施：

GTA182片推荐剂量+甲磺酸伏美替尼片

干预措施代码：

Intervention：

GTA182 tablets at the recommended dose + Vumetostat Mesylate Tablets

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 上海市 

市(区县)：

  

Country：

China 

Province：

Shanghai 

City：

 

单位(医院)：

上海市胸科医院 

单位级别：

三级甲等 

Institution
hospital：

Shanghai Chest?Hospital

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 浙江省 

市(区县)：

  

Country：

China 

Province：

Zhejiang 

City：

 

单位(医院)：

浙江省台州医院 

单位级别：

三级甲等 

Institution
hospital：

Taizhou Hospital of Zhejiang Province

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 江西省 

市(区县)：

  

Country：

China 

Province：

Jiangxi 

City：

 

单位(医院)：

南昌大学第一附属医院 

单位级别：

三级甲等 

Institution
hospital：

The First Affiliated Hospital of Nanchang 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)：

湖南省肿瘤医院 

单位级别：

三级甲等 

Institution
hospital：

Hunan Provincial Tumor 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)：

四川大学华西医院 

单位级别：

三级甲等 

Institution
hospital：

West China Hospital of Sichuan University

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 浙江省 

市(区县)：

  

Country：

China 

Province：

Zhejiang 

City：

 

单位(医院)：

浙江大学医学院附属邵逸夫医院 

单位级别：

三级甲等 

Institution
hospital：

Shao Yi Fu Hospital, Affiliated to the School of Medicine of Zhejiang University

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 Provincial 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 

单位级别：

三级甲等 

Institution
hospital：

Shandong First Medical University Affiliated Tumor 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 Provincial Cancer 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)：

浙江省肿瘤医院 

单位级别：

三级甲等 

Institution
hospital：

Zhejiang Provincial 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 Provincial Cancer 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）发生率和严重程度

指标类型：

主要指标

Outcome：

Incidence and severity of dose-limiting toxicities (DLTs)

Type：

Primary indicator

测量时间点：

首个给药周期的 1天至第 21 天

测量方法：

临床观察、体格检查、生命体征监测及实验室检查等，根据美国国家癌症研究所常见不良事件评价标准（NCI CTCAE）V5.0 进行安全性评估

Measure time point of outcome：

Day 1 to Day 21 of Cycle 1

Measure method：

Clinical observation, physical examination, vital signs monitoring, laboratory tests, etc., and safety evaluation according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V5.0

指标中文名：

TEAEs、TRAEs 和 SAEs 的发生率和严重程度

指标类型：

主要指标

Outcome：

Incidence and severity of TEAEs, TRAEs, and SAEs

Type：

Primary indicator

测量时间点：

首次接受试验药物起至末次用药后 30 天（或至开始新的抗肿瘤治疗前）

测量方法：

临床观察、体格检查、生命体征监测及实验室检查等，根据美国国家癌症研究所常见不良事件评价标准（NCI CTCAE）V5.0 进行安全性评估

Measure time point of outcome：

From the first dose of the investigational drug to 30 days after the last dose (or to before startin

Measure method：

Clinical observation, physical examination, vital signs monitoring, laboratory tests, etc., and safety evaluation according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V5.0

指标中文名：

药代动力学特征

指标类型：

次要指标

Outcome：

Pharmacokinetic characteristics

Type：

Secondary indicator

测量时间点：

第 1 周期第 1 天、第 1 周期第 8天、第 1 周期第 15 天、第 2 周期第 1 天、第 3-5 周期第 1 天、治疗终止时

测量方法：

药代动力学参数，包括但不限于Cmax、Tmax、AUC0-tAUC0-∞、λz、t1/2、CLz/FVz/F、MRT

Measure time point of outcome：

Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3-5 Day 1, at treatment discontin

Measure method：

Pharmacokinetic parameters including but not limited to Cmax, Tmax, AUC0-t, AUC0-∞, λz, t1/2, CLz/FVz/F, MRT

指标中文名：

ORR，DoR， DCR 和PFS， TTR

指标类型：

次要指标

Outcome：

ORR，DoR， DCR and PFS， TTR

Type：

Secondary indicator

测量时间点：

首次给予研究治疗前 28 天、首次接受试验药物开始，每 6 周±7 天进行一次，治疗终止时

测量方法：

计算机断层扫描（CT）和/或磁共振成像（MRI）检查，基于实体瘤疗效评估标准（RECIST）V1.1 评估

Measure time point of outcome：

Every 6 weeks ±7 days from the first dose of study treatment, at the beginning of the first dose of

Measure method：

Computed tomography (CT) and/or magnetic resonance imaging (MRI) examinations, evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) V1.1

指标中文名：

与 GTA182 疗效相关的生物标志物-SDMA

指标类型：

次要指标

Outcome：

Biomarkers associated with GTA182 efficacy - SDMA

Type：

Secondary indicator

测量时间点：

C1D1 和 C3D1 给药前

测量方法：

LC-MS

Measure time point of outcome：

C1D1 and C3D1 predose

Measure method：

LC-MS

指标中文名：

与 GTA182 疗效相关的生物标志物-ctDNA

指标类型：

次要指标

Outcome：

Biomarker Correlates with GTA182 Efficacy – ctDNA

Type：

Secondary indicator

测量时间点：

基线、给药 2 周 期后及停止用药时

测量方法：

NGS-血液

Measure time point of outcome：

Baseline, after Cycle 2, and at time of discontinuation

Measure method：

NGS-blood

指标中文名：

与 GTA182 疗效相关的生物标志物-组织样本的基因突变特征

指标类型：

次要指标

Outcome：

Biomarker-Gene Mutation Profiling in Tissue Samples Associated with GTA182 Efficacy

Type：

Secondary indicator

测量时间点：

基线

测量方法：

NGS-组织样本

Measure time point of outcome：

Baseline

Measure method：

NGS-Tissue sample

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

血液

组织：

Sample Name：

Blood

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

标本中文名：

肿瘤组织

组织：

Sample Name：

tumor tissue

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

征募研究对象情况：

Recruiting status：

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

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）：

研究结束后申办方将EDC数据刻盘提供至研究中心。 根据研究协议，研究中产生的注册上市的任何数据资料将属于申办方的产权。利用我国人类遗传资源开展国际合作科学研究，各方承诺保证中方单位及其研究人员在合作期间全过程、实质性地参与研究，研究过程中的所有记录以及数据信息等完全向中方单位开放并向中方单位提供备份。本项目包含探索性研究，利用中国人类遗传资源开展国际合作科学试验，产生的新发明、新发现产生的成果申请专利的，由申办方和研究机构共同提出申请，专利权归合作双方共有。探索性研究项下产生的数据，著作以及专利等研究成果均双方共有。

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

The sponsor provided debossed EDC data to the sites at the end of the study.According to the study agreement, any data and materials generated for registration and listing in the study will belong to the property rights of the Sponsor, and the parties undertake to ensure that the Chinese unit and its investigators participate in the whole process and materially in the study during the cooperation period, and all records and data information in the process of the study are completely open to the Chinese unit and provide backups to the Chinese unit. This project includes exploratory research, international collaborative scientific experiments using Chinese human genetic resources, new inventions and discoveries generated, and patent application for the results generated, which will be jointly applied for by the Sponsor and the research institution, and the patent rights will be shared by both parties.

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：

本研究的数据使用EDC系统Medidata Rave进行采集和管理。

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

The EDC system Medidata Rave was used for data collection and management in this study.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2026-06-22 14:27:05