肿瘤细胞治疗研究
英文原题：A Study to Evaluate the Safety and Efficacy of A2B395, an Allogeneic Logic-gated CAR T, in Participants With Solid Tumors That Express EGFR and Have Lost HLA-A*02 Expression
⚠ 该试验的登记信息已有 13 个月未更新， 页面上显示的「招募中」可能已经失效。联系研究中心之前，建议先到 ClinicalTrials.gov 核对登记原文的最新状态与联系方式。
这是一项 I/II 期注册临床试验，评估细胞治疗用于实体瘤、结直肠癌、急性淋巴细胞白血病的安全性、可行性及初步疗效。当前状态：招募中。计划入组 240 例。试验地点：美国 · 吉尔伯特、拉霍亚、洛杉矶、杰克逊维尔（共 10 个中心）。登记号：NCT06682793。
不限性别 · ≥ 18 Years
主要入选标准 1. 已按规定入组A2 Biotherapeutics, Inc.的BASECAMP-1研究；组织样本经二代测序（NGS）证实HLA-A*02杂合性丢失（LOH），尽可能使用原发部位样本。 2. 组织学确诊为复发、不可切除、局部晚期或转移性结直肠癌（CRC）、非小细胞肺癌（NSCLC）、头颈部鳞状细胞癌（HNSCC）、三阴性乳腺癌（TNBC）、肾细胞癌（RCC）或其他表达EGFR的实体瘤。须有可测量病灶，CT测量病灶≥1.0 cm。 3. 已按方案要求接受相应实体瘤的既往治疗。 4. 器官功能符合方案要求。 5. ECOG体能状态评分0至1。 6. 预期寿命≥3个月。 7. 愿意遵守研究评估安排，包括长期安全性随访。 主要排除标准 1. 病情适合局部治疗，或可接受具有治疗目的而非姑息目的的标准治疗。 2. 既往接受异基因造血干细胞移植。 3. 既往接受实体器官移植。 4. A2B395输注前3周内或3个半衰期内接受抗癌治疗。 5. A2B395输注前28天内接受放疗。 6. 过去6个月内有不稳定型心绞痛、心律失常、心肌梗死或其他显著心脏病。 7. 入组前3个月内发生新的症状性肺栓塞（PE）或深静脉血栓（DVT）。若PE或DVT发生距入组超过3个月且已充分治疗，允许接受治疗剂量抗凝药物。 8. 过去1年内有间质性肺病病史（包括药物诱发的间质性肺病和放射性肺炎），且需要长期使用类固醇或其他免疫抑制剂治疗。 9. 需要在家补充氧气。 10. 有生育能力且妊娠或哺乳的女性。 11. 有生育能力的男性或女性受试者不同意从签署知情同意书起至A2B395输注后6个月采取避孕措施。
Inclusion Criteria: Key Inclusion Criteria: 1. Appropriately enrolled in the BASECAMP-1 A2 Biotherapeutics, Inc. study, with tissue demonstrating LOH of HLA-A\*02 by NGS (whenever possible from the primary site). 2. Histologically confirmed recurrent unresectable, locally advanced, or metastatic CRC, NSCLC, HNSCC, TNBC, RCC, or other solid tumors with EGFR expression. Measurable disease is required with lesions of ≥1.0 cm by CT. 3. Received previous required therapy for the appropriate solid tumor disease as described in the protocol 4. Has adequate organ function as described in the protocol 5. ECOG performance status of 0 to 1 6. Life expectancy of ≥3 months 7. Willing to comply with study schedule of assessments including long-term safety follow-up Key Exclusion Criteria: 1. Has disease that is suitable for local therapy or able to receive standard of care therapy that is therapeutic and not palliative 2. Prior allogeneic stem cell transplant 3. Prior solid organ transplant 4. Cancer therapy within 3 weeks or 3 half lives of A2B395 infusion 5. Radiotherapy within 28 days of A2B395 infusion 6. Unstable angina, arrhythmia, myocardial infarction, or any other significant cardiac disease within the last 6 months 7. Any new symptomatic pulmonary embolism (PE) or a deep vein thrombosis (DVT) within 3 months of enrollment. Therapeutic dosing of anticoagulants is allowed for history of PE or DVT if greater than 3 months from time of enrollment, and adequately treated 8. History of interstitial lung disease including drug-induced interstitial lung disease and radiation pneumonitis that requires treatment with prolonged steroids or other immune suppressive agents within 1 year 9. Requires supplemental home oxygen 10. Females of childbearing potential who are pregnant or breastfeeding 11. Subjects, both male and female, of childbearing potential who are not willing to practice birth control from the time of consent through 6 months post infusion of A2B395
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：Phase 1: Rate of adverse events and dose limiting toxicities (DLTs) by dose level · Adverse events and toxicity will be evaluated according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (or current version). Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and graft versus host disease (GvHD) events will be graded according to the criteria described in the current protocol. · From the time of Informed consent until 24 months (2 years) post A2B395 infusion；Phase 1: Recommended phase 2 dose (RP2D) · The RP2D will be identified utilizing a BOIN study design in addition to considering safety and biomarker analysis. · 28 days post A2B395 infusion；Phase 2: The overall response rate (ORR) for patients · The ORR will be evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and assessed by independent central review. · 24 months post A2B395 infusion
次要终点：Persistence of A2B395；Cytokine analysis；Cytokine analysis
受试者先接受预处理淋巴清除（PCLD）方案，随后在第0天静脉输注一次A2B395。
本研究旨在评估A2B395（一种异基因、逻辑门控Tmod™ CAR-T细胞产品）在实体瘤受试者中的表现，包括结直肠癌（CRC）、非小细胞肺癌（NSCLC）、头颈部鳞状细胞癌（HNSCC）、三阴性乳腺癌（TNBC）、肾细胞癌（RCC）及其他表达EGFR且HLA-A*02表达缺失的实体瘤。 研究主要拟回答： • I期：A2B395的安全推荐剂量是多少？ • II期：推荐剂量的A2B395能否杀伤实体瘤细胞并保护患者的健康细胞？ 受试者须完成研究规定的操作和评估，并接受以下研究治疗： • 入组BASECAMP-1研究（NCT04981119）； • 接受预处理淋巴清除（PCLD）方案； • 按分配剂量接受Tmod CAR-T细胞A2B395治疗。
The goal of this study is to test A2B395, an allogeneic logic-gated Tmod™ CAR T-cell product in subjects with solid tumors including colorectal cancer (CRC), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), triple-negative breast cancer (TNBC), renal cell carcinoma (RCC) and other solid tumors that express EGFR and have lost HLA-A\*02 expression. The main questions this study aims to answer are: * Phase 1: What is the recommended dose of A2B395 that is safe for patients * Phase 2: Does the recommended dose of A2B395 kill the solid tumor cells and protect the patient's healthy cells Participants will be required to perform study procedures and assessments, and will also receive the following study treatments: * Enrollment in BASECAMP-1 (NCT04981119) * Preconditioning lymphodepletion (PCLD) regimen * A2B395 Tmod CAR T cells at the assigned dose
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