肿瘤细胞治疗研究
英文原题：BCMA/CD3 Bispecific Antibody as Bridging Therapy Before CAR-T Cell Infusion in RRMM
这是一项 I 期注册临床试验，评估 BCMA 细胞治疗用于多发性骨髓瘤的安全性、可行性及初步疗效。当前状态：尚未开始招募。计划入组 10 例。登记号：NCT07407010。
不限性别 · ≥ 18 Years
纳入标准： 1. 自愿参加，能够理解并签署知情同意书； 2. 年龄≥18岁； 3. 按《中国多发性骨髓瘤诊治指南（2022年修订版）》确诊有症状的多发性骨髓瘤； 4. 复发/难治性多发性骨髓瘤符合以下任一项：三类药物难治（至少对1种免疫调节药物[IMiD]、1种蛋白酶体抑制剂[PI]及1种抗CD38单克隆抗体耐药）；五种药物难治（至少对2种IMiD、2种PI及1种抗CD38抗体耐药）；或继发性浆细胞白血病（sPCL），即符合上述指南的多发性骨髓瘤诊断，且外周血浆细胞占白细胞≥20%或循环浆细胞绝对值>2×10⁹/L； 5. 成功完成CAR-T细胞制备用单采； 6. ECOG体能状态评分≤3分； 7. 无活动性感染：HBV-DNA阴性、HCV-RNA阴性、HIV阴性； 8. 肝功能：总胆红素<1.5×ULN（Gilbert综合征患者<3×ULN），AST/ALT<3×ULN； 9. 肾功能：按Cockcroft-Gault公式计算的肌酐清除率（CrCl）≥30 mL/min； 10. 基线室内空气下血氧饱和度>92%； 11. 筛查前7天内血液学指标：白细胞≥1.0×10⁹/L、中性粒细胞绝对计数≥1.0×10⁹/L、血红蛋白≥70 g/L、血小板≥75×10⁹/L（骨髓浆细胞≥50%者≥50×10⁹/L）。研究者可根据临床理由酌情判断； 12. 生长因子限制：促红细胞生成素、G-CSF、GM-CSF或血小板生成素受体激动剂（如艾曲泊帕）须停药洗脱2周； 13. 生殖要求：无生育能力女性可入组；有生育能力女性筛查时血清/尿液β-hCG妊娠检测须阴性； 14. 有生育能力的男女须在治疗期间及CAR-T输注后至少3个月内采取有效避孕措施，具体由研究者判断； 15. 男性须自筛查起至治疗后90天内不捐献精子； 16. 愿意且能够完成研究程序和随访。 排除标准： 1. 既往接受过靶向GPRC5D的免疫治疗； 2. 研究者评估认为存在GPRC5D×CD3双特异性抗体治疗禁忌证，如不适合该治疗的严重心肺疾病； 3. 筛查时周围神经病变>2级，或疼痛性神经病变≥2级（不论目前是否用药）； 4. 已知对GPRC5D×CD3双特异性抗体成分不耐受、过敏或有禁忌证； 5. 已开始BCMA CAR-T细胞治疗的桥接治疗； 6. 存在不稳定/活动性心脑血管疾病，包括：a.首剂前180天内不稳定型心绞痛、有症状心肌缺血、心肌梗死或冠状动脉血运重建；b.未控制高血压（>140/90 mmHg，且过去6个月内曾有>180/100 mmHg记录）；c.有临床意义且未控制的心律失常（无症状I度房室传导阻滞、左前分支阻滞或右束支传导阻滞除外）；d.超声心动图LVEF<40%；e.筛查前12个月内卒中或颅内出血；f.治疗前严重血栓事件； 7. 活动性HIV感染或血清学阳性； 8. 活动性HBV/HCV感染：HBV HBsAg阳性者须经PCR证实HBV-DNA阴性（抗病毒治疗且病毒已抑制者可允许）；HCV抗体阳性者须HCV-RNA PCR阴性； 9. 妊娠或哺乳； 10. 影响吞咽或药物吸收的活动性胃肠道疾病； 11. 入组前2周内接受大手术，或研究期间计划接受大手术（椎体后凸成形术/椎体成形术除外；局部麻醉程序允许）； 12. 首次研究给药前4周内接种活疫苗； 13. 研究者判断存在影响依从性或知情同意能力的活动性精神/躯体疾病； 14. 对必需合并用药或支持治疗存在禁忌证； 15. 任何妨碍研究程序的情况； 16. 无法或不愿遵守方案。
Inclusion Criteria: * 1.Voluntary Participation: Ability to understand and voluntarily sign the informed consent form (ICF).2.Age ≥18 years.3.Confirmed symptomatic MM diagnosis per the Chinese Guidelines for Diagnosis and Management of Multiple Myeloma (2022 Revision).4.Relapsed/Refractory MM (RRMM) meeting one of the following:Triple-class refractory RRMM: Resistant to ≥1 immunomodulatory drug (IMiD), ≥1 proteasome inhibitor (PI), and ≥1 anti-CD38 monoclonal antibody.Penta-drug refractory RRMM: Resistant to ≥2 IMiDs, ≥2 PIs, and ≥1 anti-CD38 antibody.Secondary plasma cell leukemia (sPCL):MM diagnosis per Chinese Guidelines (2022), plusPeripheral blood plasma cells ≥20% of leukocytes or absolute circulating plasma cells \>2×10⁹/L.5.Successful apheresis for CAR-T cell manufacturing.6.ECOG performance status ≤3.7.No active infections:HBV-DNA negative, HCV-RNA negative, HIV negative.8.Liver function:Total bilirubin \<1.5×ULN (\<3×ULN for Gilbert's syndrome).AST/ALT \<3×ULN.9.Renal function: Calculated CrCl ≥30 mL/min (Cockcroft-Gault formula).10.Baseline oxygen saturation \>92% (room air).11.Hematologic criteria (within 7 days of screening):WBC ≥1.0×10⁹/L, ANC ≥1.0×10⁹/L, hemoglobin ≥70 g/L, andPlatelets ≥75×10⁹/L (or ≥50×10⁹/L if bone marrow plasma cells ≥50%).Investigator discretion permitted for clinical justification.12.Growth factor restrictions:2-week washout required for erythropoietin, G-CSF, GM-CSF, or thrombopoietin agonists (e.g., eltrombopag).13.Reproductive requirements:Non-childbearing women eligible;Childbearing potential women: Negative serum/urine pregnancy test (β-hCG) at screening.14.Contraception:Males/females of reproductive potential must use effective contraception (per investigator judgment) during treatment and for ≥3 months post CAR-T infusion.15.Sperm donation prohibition: Males must refrain from sperm donation from screening until 90 days post-treatment.16.Compliance: Willing and able to complete study procedures and follow-up. Exclusion Criteria: * 1.Prior GPRC5D-targeted immunotherapy.2.Investigator-assessed contraindications to GPRC5D×CD3 bispecific antibody therapy (e.g., severe cardiopulmonary diseases incompatible with treatment).3.Grade \>2 peripheral neuropathy or ≥grade 2 painful neuropathy at screening (regardless of current medication).4.Known intolerance, hypersensitivity, or contraindication to GPRC5D×CD3 bispecific antibody components.5.Initiation of bridging therapy for BCMA CAR-T cell treatment.6.Unstable/active cardiovascular or cerebrovascular disease, including any of:a. Unstable angina, symptomatic myocardial ischemia, myocardial infarction, or coronary revascularization within 180 days prior to first dose.b. Uncontrolled hypertension (\>140/90 mmHg with historical readings \>180/100 mmHg within 6 months).c. Clinically significant uncontrolled arrhythmias (excluded: asymptomatic 1st-degree AV block or LAFB/RBBB).d. LVEF \<40% by echocardiography.e. Stroke or intracranial hemorrhage within 12 months before screening.f. Pre-treatment severe thrombotic events.7.Active HIV infection or seropositivity.8.Active HBV/HCV infection:HBV: HBsAg(+) requires confirmed negative HBV-DNA PCR (allowed: if on antiviral therapy with confirmed suppression).HCV: HCV Ab(+) requires negative HCV-RNA PCR.9.Pregnancy or lactation.10.Active gastrointestinal disorders affecting swallowing or drug absorption.11.Major surgery within 2 weeks pre-enrollment or planned during study (excluded: kyphoplasty/vertebroplasty; allowed: local anesthesia procedures).12.Live vaccines within 4 weeks before first study dose.13.Active psychiatric/medical conditions impairing compliance/consent capacity per investigator judgment.14.Contraindications to required concomitant medications/supportive care.15.Any condition interfering with study procedures.16.Inability/unwillingness to comply with protocol.
以上为辅助阅读译文。是否适合入组须由主治医生判断，最终以登记平台与研究者确认为准。
主要终点：Overall Response Rate (ORR) · The proportion of subjects achieving stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) after treatment with CM336 injection · Minimum 2 years after infusion；Safety and Tolerability · The incidence of treatment-emergent adverse events (TEAES) · Minimum 2 years after infusion
次要终点：Time to Response (TTR)；Duration of Response (DOR)；Overall Survival (OS)；Progression-Free Survival (PFS)
这是一项前瞻性、单臂、多中心试验，评估复发/难治性多发性骨髓瘤（RRMM）患者在CAR-T细胞输注前接受BCMA/CD3双特异性抗体桥接治疗的血液学缓解率和安全性。
This study is a prospective, single-arm, multicenter trial designed to evaluate the hematologic response rate and safety of BCMA/CD3 bispecific antibody bridging therapy prior to CAR-T cell infusion in patients with relapsed/refractory multiple myeloma (RRMM).
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