结直肠癌(CRC)是全球男性和女性中第三大最常见的癌症。在转移阶段,治疗选择和预后有限。为了解决这一患者群体的高医疗需求,我们产生了称为CC-3的CD276xCD3双特异性抗体。CD276在CRC细胞和肿瘤血管上表达,从而允许“双重”抗癌作用。
■这项首次人体临床研究计划作为一项前瞻性多中心试验,接受三行治疗后的转移性CRC患者。在剂量递增部分,最初,采用单患者队列的加速滴定设计.这里,每位患者将接受固定剂量水平(从第一位患者的50µg开始);然而,患者之间,剂量水平可以增加高达100%,取决于安全审查委员会的决定。发生任何不良事件(AE)≥2级,剂量限制性毒性(DLT)时,或达到≥800µg的剂量水平,升级将切换到标准的3+3剂量设计。在确定最大耐受剂量(MTD)后,定义为不超过六名患有DLT的患者之一,另外14例患者在剂量扩展阶段接受了MTD水平的CC-3.主要终点是AE的发生率和严重程度,以及根据实体瘤反应评估标准(RECIST)对治疗的最佳客观反应1.1。次要终点包括整体安全性,功效,生存,生活质量,和药代动力学研究。
■CD276xCD3研究得到杜塞尔多夫海涅大学医学院伦理委员会和保罗-埃利希研究所(P00702)的批准。临床试验结果将发表在同行评审的期刊上。试验登记号:临床试验。cov登记处(NCT05999396)和欧盟临床试验登记处(欧盟试验号2022-503084-15-00)。
UNASSIGNED: Colorectal cancer (CRC) is the third most common cancer worldwide in men and women. In the metastasized stage, treatment options and prognosis are limited. To address the high medical need of this patient population, we generated a CD276xCD3 bispecific antibody termed CC-3. CD276 is expressed on CRC cells and on tumor vessels, thereby allowing for a \"dual\" anticancer effect.
UNASSIGNED: This first-in-human clinical study is planned as a prospective multicenter trial, enrolling patients with metastatic CRC after three lines of therapy. During the dose-escalation part, initially, an accelerated titration design with single-patient cohorts is employed. Here, each patient will receive a fixed dose level (starting with 50 µg for the first patient); however, between patients, dose level may be increased by up to 100%, depending on the decision of a safety review committee. Upon occurrence of any adverse events (AEs) grade ≥2, dose-limiting toxicity (DLT), or reaching a dose level of ≥800 µg, the escalation will switch to a standard 3 + 3 dose design. After maximum tolerated dose (MTD) has been determined, defined as no more than one of the six patients experiencing DLT, an additional 14 patients receive CC-3 at the MTD level in the dose-expansion phase. Primary endpoints are incidence and severity of AEs, as well as the best objective response to the treatment according to response evaluation criteria in solid tumors (RECIST) 1.1. Secondary endpoints include overall safety, efficacy, survival, quality of life, and pharmacokinetic investigations.
UNASSIGNED: The CD276xCD3 study was approved by the Ethics Committee of the Medical Faculty of the Heinrich Heine University Düsseldorf and the Paul-Ehrlich-Institut (P00702). Clinical trial results will be published in peer-reviewed journals. Trial registration numbers: ClinicalTrials.cov Registry (NCT05999396) and EU ClinicalTrials Registry (EU trial number 2022-503084-15-00).