ChiCTR2400093606 版本V1.0 版本创建时间2024/12/09 14:44:39 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：

 ChiCTR2400093606 

最近更新日期：

Date of Last Refreshed on：

 2024-12-09 14:44:28 

注册时间：

Date of Registration：

 2024-12-09 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

DGKa 抑制剂BAY 2862789 治疗晚期实体瘤的FiH试验

Public title：

DGKalpha inhibitor BAY 2862789 FiH trial in advanced solid cancers

注册题目简写：

English Acronym：

研究课题的正式科学名称：

一项开放性、I期、首次人体的剂量递增和剂量扩展，旨在评价二酰基甘油激酶α抑制剂（DGKai）BAY2862789治疗晚期实体瘤研究参与者的安全性、耐受性、最大耐受或最大给药剂量、药代动力学、药效学和肿瘤缓解特征的研究

Scientific title：

An open-label, phase 1, first-in-human, dose escalation and expansion study to evaluate the safety, tolerability, maximum tolerated or administered dose, pharmacokinetics, pharmacodynamics, and tumor response profile of the diacylglycerol kinase alpha inhibitor (DGKai) BAY 2862789 in participants 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：

王卓 

研究负责人：

程颖 

Applicant：

Zhuo Wang 

Study leader：

Cheng Ying 

申请注册联系人电话：

Applicant telephone：

 +86 18280187206

研究负责人电话：

Study leader's
telephone：

+86 431 80596315

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：

 zhuo.wang2@bayer.com

研究负责人电子邮件：

Study leader's E-mail：

 jl.cheng@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：

北京市朝阳区东大桥路9号

研究负责人通讯地址：

吉林省长春市湖光路1018号、锦湖大路1066号

Applicant address：

9 Dongdaqiao Road, Chaoyang District, Beijing

Study leader's address：

No. 1018 Huguang Road, No. 1066 Jinhu Road, Changchun City, Jilin 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：

拜耳医药保健有限公司

Applicant's institution：

Bayer AG

研究负责人所在单位：

吉林省肿瘤医院

Affiliation of the Leader：

Jilin 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：

 202405-039-01

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：

吉林省肿瘤医院伦理委员会

Name of the ethic committee：

Jilin Province Cancer Hospital Institutional Review Board

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-05-30 00:00:00

伦理委员会联系人：

张宁

Contact Name of the ethic committee：

Zhang Ning

伦理委员会联系地址：

吉林省长春市湖光路1018号、锦湖大路1066号

Contact Address of the ethic committee：

No. 1018 Huguang Road, No. 1066 Jinhu Road, Changchun City, Jilin Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 431 80596067

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 JPCHIRB@163.com

研究实施负责（组长）单位：

吉林省肿瘤医院

Primary sponsor：

Jilin Cancer Hospital

研究实施负责（组长）单位地址：

吉林省长春市湖光路1018号、锦湖大路1066号

Primary sponsor's address：

No. 1018 Huguang Road, No. 1066 Jinhu Road, Changchun City, Jilin 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)：

吉林

市(区县)：

Country：

China

Province：

Jilin

City：

单位(医院)：

吉林省肿瘤医院

具体地址：

吉林省长春市湖光路1018号、锦湖大路1066号

Institution
hospital：

Jilin Cancer Hospital

Address：

No. 1018 Huguang Road, No. 1066 Jinhu Road, Changchun City, Jilin Province

经费或物资来源：

拜耳医药保健有限公司

Source(s) of funding：

Bayer AG

研究疾病：

晚期实体瘤  

Target disease：

Advanced solid 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：

主要目的： 1.确定BAY2862789在晚期实体瘤研究参与者中的安全性和耐受性； 2.确定BAY2862789在晚期实体瘤研究参与者中的最大耐受剂量（MTD）或最大给药剂量（MAD），以及推荐II期剂量（RP2D）； 3. 描述口服BAY 2862789 的PK 特征 次要目的： 1. 初步评估BAY 2862789 在晚期实体瘤中 的抗肿瘤活性 2. 评估BAY 2862789 治疗后免疫相关药效学生物标志物的变化 其他预先规定的目的： 1. 确定药理学活性剂量（PAD） 2. 确认BAY 2862789 治疗后肿瘤免疫相关药效学生物标志物的变化 3. 探索血液和肿瘤中与BAY 2862789 安全性和/或临床有效性相关的任何分子学特征 4. 考察PK/药效学生物标志物与安全性和/或有效性的关系（如可行） 5. 使用连续的血液和肿瘤样本探索新的作用机制 6. 评估BAY 2862789 液体制剂（LSF）和片剂的相对生物利用度 7. 进一步评价研究干预和相似药物（如作用机制相关效应、安全性），并评价与癌症和相关健康问题有关的病理机制  

Objectives of Study：

Primary Objectives: 1. To determine the safety and tolerability of BAY2862789 in study participants with advanced solid tumors; 2. To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of BAY2862789 in study participants with advanced solid tumors, as well as the recommended Phase II dose (RP2D); 3. To describe the PK profile of oral BAY 2862789 Secondary Purpose: 1. Initial evaluation of BAY 2862789 in advanced solid tumors antitumor activity 2. To assess changes in immune-related pharmacodynamic biomarkers after BAY 2862789 treatment Other pre-specified purposes: 1. Determination of the pharmacologically active dose (PAD) 2. To confirm changes in tumor immune-related pharmacodynamic biomarkers after BAY 2862789 treatment 3. Explore any molecular features in blood and tumors that are relevant to the safety and/or clinical efficacy of BAY 2862789 4. Examine the relationship between PK/pharmacodynamic biomarkers and safety and/or efficacy (if feasible) 5. Explore novel mechanisms of action using serial blood and tumor samples 6. To evaluate the relative bioavailability of BAY 2862789 liquid formulations (LSF) and tablets 7. Further evaluation of research interventions and similar drugs (e.g., mechanism-of-action related effects, safety), and evaluation of pathological mechanisms related to cancer and related health problems

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

知情同意 1. 能够按照附录 1（第 10.1.3 节）所述签署知情同意书，包括遵守知情同意书（ICF）和本方案中列出的要求和限制。 2. 在签署知情同意书之日，研究参与者的年龄>=18 岁。研究参与者类型和疾病特征 3. 经当地研究中心研究者评估，有符合 RECIST 1.1 标准的可测量病灶。位于既往接受过放疗或局部治疗区域的病灶出现进展，则认为是可测量病灶。 4. ECOG 体能状态评分为 0-1。 5. 对于经组织学检查确诊为实体瘤的研究参与者，已用尽对该肿瘤类型已知有益的标准治疗，或对标准治疗无法接受，且参加本试验是一种合理的选择，可以入选。入组试验前，应根据当地国家指南进行适当的肿瘤分子特征分析。如果研究参与者存在已知可靶向治疗的基因组畸变，则其还应接受过研究者认为适当的可用靶向药物治疗。 研究不同部分的标准如下： 1）剂量递增：所有实体瘤，原发性中枢神经系统癌除外。 2）mini-PAD 队列：符合这些队列条件的研究参与者必须既往接受过适用的抗 PD-1/PD-L1 治疗。这些研究参与者必须在接受该方案治疗的前 12 周内出现过影像学的缓解或达到疾病稳定状态，且随后在接受该方案治疗期间出现疾病进展【如果研究参与者继续接受含抗 PD1/L1 药物的方案治疗，继而又出现缓解，亦具备入选资格】。 mini-PAD 队列可招募以下肿瘤类型： （1）NSCLC：研究参与者必须接受过针对转移性疾病最多两线的标准治疗（包括含铂治疗方案）。在完成已批准的抗 PD-1/PD-L1 药物辅助治疗后 6 个月内出现疾病进展的研究参与者有资格参加研究。携带 EGFR 或 ALK 突变的 NSCLC 研究参与者 不具备入选资格。 （2） 胃/GEJ 腺癌：研究参与者可接受过针对转移性疾病最多两线的标准治疗。如果 HER2 为阳性，则研究参与者必须接受过抗 HER2 的标准治疗，允许既往接受过最多三线的 HER2 靶向治疗。 （3） MMR 缺陷/ MSI 高不稳定性 CRC 肿瘤：MSI 高不稳定性按当地标准治疗确定 MSI 高不稳定性状态（基于从患者记录中获得的当地批准/许可方法，例如 FoundationOne CDx、OncoMateMSI Dx、VENTANA MMR RxDx Panel、Guardant360 CDx 的历史检测结果）。该队列中的研究参与者可接受最多三线的标准治疗。 （4） 黑色素瘤：可接受过针对转移性疾病的最多两线的标准治疗的BRAF 阴性研究参与者。接受过最多三线治疗的 BRAF 阳性肿 瘤研究参与者。因靶向治疗不可接受或不可用而未接受过BRAF 抑制剂单药治疗或与 MEK 抑制剂联合治疗的 BRAF 阳性肿瘤研究参与者亦有资格参加研究。在完成已批准的抗 PD-1/PD-L1 药物辅助治疗后 6 个月内出现疾病进展的研究参与者有资格参加研究（葡萄膜和粘膜黑色素瘤除外）。 不符合上述最多治疗线标准的研究参与者可在与申办方讨论后入组。 扩展队列将招募以下肿瘤类型： 6. NSCLC：NSCLC 研究参与者必须接受过含获批 PD1/L-1 药物的方案和含铂化疗（如适用）。如果研究参与者存在已知可靶向治疗的基因组畸变，则其应接受过研究者认为合适的靶向药物治疗（携带 EGFR 或 ALK突变的 NSCLC 研究参与者不具备入选资格）。 7. 强制要求剂量递增队列的所有研究参与者在基线时提供存档肿瘤样本。存档肿瘤样本必须在筛选前 1 年内获得，最好在最后一次抗肿瘤治疗后 采样获取。不接受研究参与者任何的骨病灶样本或细针抽吸活检样本。如果存档材料不可用，可进行新鲜肿瘤活检（不接受细针抽吸活检或骨 病灶活检，且不得从靶病灶采集活检样本）。如果新鲜肿瘤活检无法进行或从医学角度认定不安全可行，经与申办方讨论并获得其批准后，可 接受超过 1 年的存档肿瘤样本。更多详细信息参见第 8.8.2 节。 8. 入组 mini-PAD 队列和扩展队列的研究参与者必须愿意接受强制性的肿瘤配对活检（治疗前和治疗期间）。这些研究参与者必须满足： 至少有一个适合活检（安全可行）的病灶。该病灶必须是靶病灶（用于 RECIST 1.1 评估）之外的病灶。不应从靶病灶采集活检样本。理想情况下，治疗期间（和疾病进展时）活检样本应与基线肿瘤样本取自同一部位。确认疾病进展时进行活检是可选的，但强烈建议进行。更多详细信息参见第 8.8.2 节。 9. 根据下表中的定义，器官功能良好。标本必须在研究治疗开始前 7 天内采集。 10. HIV 感染的研究参与者必须正在接受抗逆转录病毒治疗（ART），并且HIV 感染/疾病控制良好，定义为： 1)接受 ART 治疗的研究参与者在筛选时的 CD4+ T 细胞计数必须>350 个细胞/mm3 2)接受 ART 治疗的研究参与者必须达到并维持病毒学抑制，定义为在筛选时和筛选前至少 12 周内，使用当地可用的检测方法确认的HIV RNA 水平低于 50 拷贝/mL 或定量下限（低于检测限） 3) 在进入研究前（D1），研究参与者必须已接受稳定的 ART 方案治疗至少 4 周，且未改变药物或调整剂量 4)正在使用的 ART 不含 CYP3A4 强诱导剂或抑制剂，预计不会与研究药物产生重叠毒性（参见第 6.7.2 节） 性别 11. 男性研究参与者必须同意在治疗期间和研究治疗末次给药后至少 6 个月内使用第 10.4.2 节（附录 10.4）中详述的避孕措施，并在此期间避免捐献精子。 12. 如果女性研究参与者未处于妊娠期（参见第 10.4.2 节[附录 10.4]）和哺乳期且至少满足以下条件之一，则有资格参加研究： 1) 不属于临床研究方案中定义的具有生育能力的女性（WOCBP）。 2) WOCBP 同意在治疗期间和研究治疗末次给药后至少 6 个月内遵循第 10.4.2 节（附录 10.4）中的避孕指南

Inclusion criteria

informed consent 1. Able to sign the informed consent form as described in Appendix 1 (Section 10.1.3), including compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and this protocol; 2. On the date of signing the informed consent, the age of the study participant >=18 years. Study participant type and disease characteristics; 3. Measurable lesions that meet RECIST 1.1 criteria, as assessed by the local study center investigator. Progression of a lesion located in an area previously treated with radiotherapy or local therapy is considered measurable; 4. ECOG performance status score of 0-1; 5. For study participants with a confirmed diagnosis of solid tumors by histological examination, who have exhausted standard therapy known to be beneficial for that tumor type, or are unacceptable to standard therapy, and participation in this trial is a reasonable option to be enrolled. Prior to enrollment in the trial, appropriate tumor molecular characterization should be performed according to local national guidelines. If the study participant has genomic aberrations known to be targetable for therapy, they should also have been treated with available targeted medications as deemed appropriate by the investigator; The criteria for studying the different parts are as follows: 1) Dose escalation: all solid tumors, except primary central nervous system cancer; 2) mini-PAD cohorts: Study participants eligible for these cohorts must have received prior appropriate anti-PD-1/PD-L1 therapy. These study participants must have had an imaging response or achieved stable disease status within the first 12 weeks of treatment with this regimen and subsequently had disease progression while receiving this regimen (study participants are also eligible if they continue to receive an anti-PD1/L1-containing regimen with subsequent remissions); The mini-PAD cohort can enroll the following tumor types: (1) NSCLC: Study participants must have received up to two lines of standard therapy (including platinum-containing regimens) for metastatic disease. Study participants with disease progression within 6 months of completion of adjuvant treatment with approved anti-PD-1/PD-L1 agents are eligible to participate in the study. NSCLC study participants harboring EGFR or ALK mutations; Not eligible for selection (2) Gastric/GEJ adenocarcinoma: Study participants have received up to two lines of standard therapy for metastatic disease. If HER2 is positive, study participants must have received anti-drugs Standard therapy for HER2, allowing prior receipt of up to three prior lines of HER2-targeted therapy; (3) MMR-deficient/MSI high-instability CRC tumors: MSI high-instability, as determined by local standard treatment, MSI high-instability status (based on local approved/licensed methods obtained from patient records, e.g., historical test results for FoundationOne CDx, OncoMateMSI Dx, VENTANA MMR RxDx Panel, Guardant360 CDx). Study participants in this cohort can receive up to three lines of standard therapy; (4) Melanoma: BRAF-negative study participants who have received up to two lines of standard therapy for metastatic disease. BRAF-positive swelling that has received up to three lines of therapy; Tumor study participants. BRAF-positive tumor study participants who have not received BRAF inhibitor monotherapy or in combination with a MEK inhibitor due to unacceptable or unavailable targeted therapy are also eligible to participate in the study. Study participants with disease progression within 6 months of completion of adjuvant therapy with approved anti-PD-1/PD-L1 agents are eligible to participate in the study (with the exception of uveal and mucosal melanoma); Study participants who do not meet the criteria for the maximum line of treatment listed above may be enrolled after discussion with the sponsor; The expansion cohort will enroll the following tumor types: 6. NSCLC: NSCLC study participants must have received a prior regimen containing an approved PD1/L-1 agent and platinum-containing chemotherapy (as applicable). Study participants should have been treated with targeted agents deemed appropriate by the investigator if they have genomic aberrations known to be targetable (NSCLC with EGFR or ALK mutations are not eligible for enrollment); 7. Mandatory for all study participants in dose escalation cohorts to provide archival tumor samples at baseline. Archival tumor samples must have been obtained within 1 year prior to screening, preferably after the last dose of antitumor therapy; Sample acquisition. No bone lesion samples or fine-needle aspiration biopsy samples from study participants will be accepted. If archival material is not available, a fresh tumor biopsy may be performed (fine-needle aspiration biopsy or bone is not acceptable Biopsy of the lesion, and biopsy samples should not be collected from the target lesion). If a fresh tumor biopsy cannot be performed or is medically determined to be unsafe and feasible, it may be done after discussion with and approval from the sponsor Archival tumor samples over 1 year old. See Section 8.8.2 for more details; 8. Study participants enrolled in the mini-PAD cohort and expansion cohort must be willing to undergo mandatory paired tumor biopsies (pre-treatment and during). These study participants must meet: At least one lesion suitable for biopsy (safe and feasible). The lesion must be a lesion other than the target lesion (for RECIST 1.1 assessment). Biopsy specimens should not be collected from target lesions. Ideally, biopsy samples should be taken from the same site as the baseline tumor sample during treatment (and at the time of disease progression). Biopsy when disease progression is confirmed is optional but highly recommended. See Section 8.8.2 for more details; 9. Good organ function as defined in the table below. Specimens must have been collected within 7 days prior to initiation of study treatment; 10. HIV-infected study participants must be on antiretroviral therapy (ART) and have good HIV infection/disease control, defined as: 1) Study participants receiving ART must have a CD4+ T cell count > 350 cells/mm3 at screening; 2) Study participants receiving ART must achieve and maintain virologic suppression, defined as HIV RNA levels below 50 copies/mL or the lower limit of quantification (below the limit of detection) confirmed at screening and for at least 12 weeks prior to screening using locally available assays; 3) Prior to study entry (D1), study participants must have been on a stable ART regimen for at least 4 weeks with no change in medication or dose adjustment; 4) ART being used does not contain strong inducers or inhibitors of CYP3A4 and is not expected to have overlapping toxicities with the study drug (see Section 6.7.2); gender; 11. Male study participants must agree to use contraception as detailed in Section 10.4.2 (Appendix 10.4) during the treatment period and for at least 6 months after the last dose of study treatment and to refrain from donating sperm during this period; 12. Female study participants are eligible to participate in the study if they are not pregnant (see Section 10.4.2 [Appendix 10.4]) and lactating and meet at least one of the following criteria: 1) Females of childbearing potential (WOCBP) who do not fall under the definition of the clinical study protocol; 2) WOCBP agrees to follow the contraception guidelines in Section 10.4.2 (Appendix 10.4) during the treatment period and for at least 6 months after the last dose of study treatment.

排除标准：

符合以下任一标准的研究参与者不得入选本研究： 医学状况 1. 在研究治疗首次给药前 24 h（尿液）或 72 h（血清）内，WOCBP 的高灵敏妊娠试验（按当地法规要求的尿液或血清妊娠试验）结果必须为阴性。如果无法确认尿检为阴性（例如，结果不明确），则需要进行血清妊娠试验。在这种情况下，如果血清妊娠试验结果为阳性，则必须将研究参与者从研究中排除; 2. 接受过异体组织/实体器官移植; 既往/合并治疗 3. 既往接受过 DGK 抑制剂治疗; 4. 既往接受过含有抗 PD-1、抗 PD-L1，或抗 PD-L2 药物，或靶向其他刺激或共抑制 T 细胞受体药物（例如，CTLA-4、OX 40、CD137）的治疗方案，并因 3 级及以上的 irAE 或任何危及生命的毒性而终止过治疗; 5. 在治疗前 4 周或 5 个半衰期内（以时间较短者为准）接受过全身性抗肿瘤治疗，包括试验用药物。参加研究前 4 周必须停止 G-CSF 等生长因子治疗; 注：研究参与者在既往治疗（全身性治疗）期间发生的所有 AE 必须已恢复至≤1 级或基线水平。存在≤2 级神经病和/或脱发的研究参与者可入选研究, 发生≤2 级需要治疗或激素替代的内分泌相关 AE 的研究参与者可入选研究。 注：如果研究参与者接受过大手术，在开始研究治疗前，手术导致的任何毒性和/或并发症必须已完全恢复 6. 研究参与者既往因放疗发生的毒性反应必须已经恢复，不需要使用皮质类固醇，且未曾出现过放射性肺炎; 7. 研究参与者在开始治疗前 2 周内不曾输过血; 8. 在研究药物首次给药前 30 天内接种过活疫苗, 活疫苗示例包括但不限于：麻疹、腮腺炎、风疹、水痘/带状疱疹（水痘）、黄热病、狂犬病、卡介苗（BCG）和伤寒疫苗。注射用季节性流感疫苗一般为灭活病毒疫苗，因此允许接种；但鼻内接种流感疫苗（例如 FluMist?）为减毒活疫苗，不允许接种; 既往/同期临床研究经历 9. 目前正在参加，或在研究治疗首次给药前 4 周内参加过试验用药物或试验用器械的研究; 注：对于已进入试验性研究随访期的研究参与者，如果距离上个试验用药物末次给药已有 4 周时间，可参加本研究; 诊断评估 10. 诊断为免疫缺陷，或在研究药物首次给药前 7 天内正在接受长期全身类固醇治疗或任何其他形式的免疫抑制治疗; 11. 已知患有其他恶性肿瘤，且在过去 3 年内出现疾病进展或需要积极治疗; 注：接受过潜在治愈性疗法的皮肤基底细胞癌、皮肤鳞状细胞癌、尿路上皮癌移行细胞癌或原位癌（例如，乳腺癌、原位宫颈癌）研究参与者无需排除。 12. 筛选时研究参与者脑部 MRI/CT 中存在新发的脑转移灶。对于既往接受过治疗的脑转移灶，如果与至少 4 周前的脑部 MRI/CT 相比，筛选时影像学提示有疾病进展，该研究参与者需从本研究中排除。对于既往接受过治疗的脑转移灶，如果与至少 4 周前的 CT/MRI 扫描结果相比，影像学提示疾病稳定，研究参与者的临床状态稳定，且在研究治疗首次给药前至少 10 天内不需要类固醇治疗，该研究参与者可入选研究。对于筛选时无症状，未经治疗的脑转移灶，接受治疗后影像学提示疾病稳定至少 4 周，并且在研究治疗首次给药前至少 10 天内不需要类固醇治疗，该研究参与者可以接受重新筛选（这些病例必须与申办方讨论并获得其同意）; 13. 原发性中枢神经系统恶性肿瘤或存在软脑膜疾病（即，脑脊液细胞学检查阳性或有明确的软脑膜受累的影像学或临床证据）; 14. 研究参与者患有可能影响口服吸收的胃肠道疾病，如短肠综合征或活动性肿瘤相关肠梗阻，且过去 6 个月内存在影响吸收的持续症状; 15. 在过去 2 年内患有需要全身治疗（即使用改善病情的药物、皮质类固醇或免疫抑制药物）的活动性自身免疫性疾病（包括炎症性肠病）。替代疗法（如甲状腺素、胰岛素、或肾上腺或垂体功能不全的生理皮质类固醇替代疗法）不属于全身治疗，允许使用。允许使用类固醇吸入剂; 16. 当前患有肺部炎症/间质性肺疾病; 17. 存在需要全身治疗的活动性感染; 18. 有卡波西肉瘤和/或多中心型 Castleman 病病史的 HIV 感染者; 19. 已知患有活动性乙肝【定义为已知阳性 HBsAg 结果】或已知存在活动性丙肝病毒【定义为检测到 HCV RNA（定性）】感染; 注：除非当地卫生监管机构强制要求，否则无需进行乙肝和丙肝检测; 20. 研究者判断曾经或目前存在可能会混淆研究结果、干扰研究参与者参与整个研究，或导致进入研究不符合研究参与者最佳利益的任何疾病证据、治疗或实验室异常检查结果; 21. 排除患有严重心血管疾病的研究参与者（例如，充血性心力衰竭、未受控制的高血压）; 22. 已知患有精神疾病或物质滥用疾病，可能干扰研究参与者配合研究要求的能力; 23. 筛选时 QT/QTc 间期显著延长（例如，反复显示 QTc 间期>470 ms）,在与申办方讨论后，使用永久性起搏器（即，起搏节律）的研究参与者或可入选研究; 24. 有尖端扭转型室性心动过速（TdP）的风险因素病史（例如，心力衰竭、长 QT 综合征家族史） 25. 在研究药物首次给药前 14 天内使用过强效 CYP3A4 抑制剂和诱导剂, 研究期间直至安全性 FU 访视期间禁止使用强效 CYP3A4 抑制剂和诱导剂（参见第 10.5 节）; 其他排除标准 26. 在研究治疗首次给药前 6 个月内接受过>30 Gy 的肺部放射治疗; 27. mini-PAD 队列和扩展队列：携带 EGFR 或 ALK 突变的 NSCLC 研究参与者不得入选研究。

Exclusion criteria：

Study participants who meet any of the following criteria must not be enrolled in this study: Medical conditions 1. Must have a negative result of a highly sensitive pregnancy test (urine or serum pregnancy test as required by local regulations) from WOCBP within 24 h (urine) or 72 h (serum) prior to the first dose of study treatment. If a negative urine test cannot be confirmed (e.g., results are inconclusive), a serum pregnancy test is required. In this case, if the serum pregnancy test result is positive, the study participant must be excluded from the study; 2. Received allogeneic tissue/solid organ transplantation; Prior/concomitant therapy 3. Prior treatment with a DGK inhibitor; 4. Prior treatment regimen containing anti-PD-1, anti-PD-L1, or anti-PD-L2 agents, or targeting other stimulatory or co-inhibitory T-cell receptor agents (e.g., CTLA-4, OX 40, CD137) and discontinued treatment due to Grade 3 or above irAEs or any life-threatening toxicity; 5. Received systemic anti-tumor therapy, including investigational agents, within 4 weeks or 5 half-lives (whichever is shorter) prior to treatment. Growth factor therapy such as G-CSF must be discontinued 4 weeks prior to enrollment in the study; Note: All AEs that occurred during prior therapy (systemic therapy) in study participants must have recovered to Grade ≤1 or baseline. Study participants with Grade ≤2 neuropathy and/or alopecia may be enrolled in the study, and study participants ≤with Grade 2 endocrine-related AEs requiring treatment or hormone replacement may be enrolled in the study. Note: If the study participant has undergone major surgery, any toxicity and/or complications resulting from the surgery must have fully recovered before initiating study treatment 6. Study participants must have recovered from previous toxicity due to radiotherapy, do not require corticosteroids, and have not had radiation pneumonitis; 7. Study participant has not had a blood transfusion within 2 weeks prior to initiation of treatment; 8. Vaccination with a live vaccine within 30 days prior to the first dose of study drug, examples of live vaccines include, but are not limited to: measles, mumps, rubella, varicella/zoster (chickenpox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccines. Seasonal influenza vaccines for injection are generally inactivated virus vaccines and are therefore permitted; However, intranasal influenza vaccines (e.g., FluMist?) are live-attenuated vaccines and are not allowed; Previous/contemporaneous clinical study experience 9. Currently enrolled, or has participated in, a study of an investigational drug or investigational device within 4 weeks prior to the first dose of study treatment; Note: For study participants who have entered the follow-up period of the pilot study, if it has been 4 weeks since the last dose of the last trial drug, they can participate in this study; Diagnostic evaluation 10. Diagnosed immunodeficiency, or is receiving long-term systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug; 11. Known other malignancies with disease progression or need for active treatment within the past 3 years; Note: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, urothelial carcinoma, transitional cell carcinoma, or carcinoma in situ (e.g., breast cancer, cervical cancer in situ) study participants who have received potentially curative therapies do not need to be excluded. 12. Presence of de novo brain metastases in the study participant's brain MRI/CT at screening. For previously treated brain metastases, study participants are excluded from this study if imaging suggests disease progression at screening compared to brain MRI/CT at least 4 weeks ago. For previously treated brain metastases, study participants may be enrolled in the study if the imaging suggests stable disease compared to CT/MRI scan results from at least 4 weeks ago, the study participant is clinically stable, and has not required steroid therapy for at least 10 days prior to the first dose of study treatment. For asymptomatic, untreated brain metastases at screening, with stable disease on imaging for at least 4 weeks after treatment, and no steroid therapy required for at least 10 days prior to the first dose of study treatment, the study participant may be re-screened (these cases must be discussed with the sponsor and obtained their consent); 13. Primary central nervous system malignancy or presence of leptomeningeal disease (i.e., positive cerebrospinal fluid cytology or clear radiographic or clinical evidence of leptomeningeal involvement); 14. Study participant has a gastrointestinal disorder that may affect oral absorption, such as short bowel syndrome or active tumor-related intestinal obstruction, and has ongoing symptoms that affect absorption within the past 6 months; 15. Active autoimmune disease (including inflammatory bowel disease) requiring systemic treatment (i.e., use of disease-modifying medications, corticosteroids, or immunosuppressive medications) within the past 2 years. Replacement therapies (such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) are not systemic therapies and are permitted. Steroid inhalers are allowed; 16. Current inflammation of the lungs/interstitial lung disease; 17. Presence of an active infection requiring systemic therapy; 18. HIV-infected individuals with a history of Kaposi's sarcoma and/or multicentric Castleman's disease; 19. Known active hepatitis B [defined as a known positive HBsAg result] or known presence of active hepatitis C virus [defined as detection of HCV RNA (qualitative)] infection; Note: Hepatitis B and C testing is not required unless mandated by local health regulators; 20. Has or is judged by the investigator to have evidence of any disease, treatment, or laboratory abnormality results that may confound the results of the study, interfere with the study participant's participation in the study as a whole, or result in entry into the study not in the best interest of the study participant; 21. Study participants with severe cardiovascular disease (e.g., congestive heart failure, uncontrolled hypertension) were excluded; 22. Known psychiatric illness or substance abuse disorder that may interfere with the study participant's ability to cooperate with the requirements of the study; 23. Study participants with a significantly prolonged QT/QTc interval at screening (e.g., repeated QTc interval >470 ms) may be enrolled in the study after discussion with the sponsor; 24. History of risk factors for torsade de pointes (TdP) (e.g., heart failure, family history of long QT syndrome) 25. Use of strong CYP3A4 inhibitors and inducers within 14 days prior to the first dose of study drug, Prohibition of strong CYP3A4 inhibitors and inducers during the study until the safety FU visit (see Section 10.5); Other Exclusion Criteria 26. Radiation therapy to the lungs of >30 Gy within 6 months prior to the first dose of study treatment; 27. mini-PAD cohorts and expansion cohorts: NSCLC study participants with EGFR or ALK mutations must not be enrolled in the study.

研究实施时间：

Study execute time：

从 From 2024-08-09 00:00:00至 To 2027-03-02 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-12-02 00:00:00 至 To 2026-08-12 00:00:00

干预措施：

Interventions：

组别：

剂量递增

样本量：

 19

Group：

Dose escalation

Sample size：

干预措施：

BAY 2862789

干预措施代码：

Intervention：

BAY 2862789

Intervention code：

组别：

Mini-PAD队列

样本量：

 30

Group：

Mini-PAD cohorts

Sample size：

干预措施：

BAY 2862789

干预措施代码：

Intervention：

BAY 2862789

Intervention code：

组别：

剂量扩展

样本量：

 32

Group：

Expansion

Sample size：

干预措施：

BAY 2862789

干预措施代码：

Intervention：

BAY 2862789

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 吉林 

市(区县)：

  

Country：

China

Province：

Jilin

City：

单位(医院)：

 吉林省肿瘤医院 

单位级别：

 三甲 

Institution
hospital：

Jilin Cancer Hospital

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)：

 华中科技大学同济医学院附属同济医院 

单位级别：

 三甲 

Institution
hospital：

Tongji Hospital, Tongji Medical College ,Huazhong University of Science and Technology

Level of the institution：

Tertiary A

测量指标：

Outcomes：

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：

前36 周期间从C1D1 起每6 周（±7 天）进行一次，此后每9 周（±7 天）进行一次

测量方法：

影像评估（RECIST 1.1标准）

Measure time point of outcome：

Tumor response evaluation assessed every 6 weeks (±7 days)

Measure method：

Tumor assessments will be performed every 6 wks (±7 d) beginning at C1D1 for the first 36 wks and every 9 wks (±7 d) thereafter during the intervention period.

指标中文名：

最大耐受剂量

指标类型：

主要指标

Outcome：

Maximum Tolerated Dose

Type：

Primary indicator

测量时间点：

首次用药后21天

测量方法：

不良事件

Measure time point of outcome：

21 days after first dose

Measure method：

Adverse events

指标中文名：

疾病控制率

指标类型：

次要指标

Outcome：

Disease control rate

Type：

Secondary indicator

测量时间点：

前36 周期间从C1D1 起每6 周（±7 天）进行一次，此后每9 周（±7 天）进行一次

测量方法：

影像评估（RECIST 1.1标准）

Measure time point of outcome：

Tumor response evaluation assessed every 6 weeks (±7 days)

Measure method：

Tumor assessments will be performed every 6 wks (±7 d) beginning at C1D1 for the first 36 wks and every 9 wks (±7 d) thereafter during the intervention period.

指标中文名：

缓解持续时间

指标类型：

次要指标

Outcome：

Duration of remission

Type：

Secondary indicator

测量时间点：

前36 周期间从C1D1 起每6 周（±7 天）进行一次，此后每9 周（±7 天）进行一次

测量方法：

影像评估（RECIST 1.1标准）

Measure time point of outcome：

Tumor response evaluation assessed every 6 weeks (±7 days)

Measure method：

Tumor assessments will be performed every 6 wks (±7 d) beginning at C1D1 for the first 36 wks and every 9 wks (±7 d) thereafter during the intervention period.

指标中文名：

无进展生存

指标类型：

次要指标

Outcome：

Progression-free survival

Type：

Secondary indicator

测量时间点：

前36 周期间从C1D1 起每6 周（±7 天）进行一次，此后每9 周（±7 天）进行一次

测量方法：

影像评估（RECIST 1.1标准）

Measure time point of outcome：

Tumor response evaluation assessed every 6 weeks (±7 days)

Measure method：

Tumor assessments will be performed every 6 wks (±7 d) beginning at C1D1 for the first 36 wks and every 9 wks (±7 d) thereafter during the intervention period.

指标中文名：

总生存期

指标类型：

次要指标

Outcome：

Overall survival

Type：

Secondary indicator

测量时间点：

前36 周期间从C1D1 起每6 周（±7 天）进行一次，此后每9 周（±7 天）进行一次

测量方法：

影像评估（RECIST 1.1标准）

Measure time point of outcome：

Tumor response evaluation assessed every 6 weeks (±7 days)

Measure method：

Tumor assessments will be performed every 6 wks (±7 d) beginning at C1D1 for the first 36 wks and every 9 wks (±7 d) thereafter during the intervention period.

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：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

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

否No

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

无

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

N/A

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网址：https://login.imedidata.com

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

EDC：https://login.imedidata.com

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2024-12-09 14:44:28