Evorpacept联合曲妥珠单抗、雷莫西尤单抗和紫杉醇治疗HER2阳性胃癌：随机2期试验
Evorpacept plus trastuzumab, ramucirumab and paclitaxel in HER2-positive gastric cancer: a randomized phase 2 trial
HER2阳性晚期胃癌患者经治后选择有限。Evorpacept（一种阻断CD47与信号调节蛋白α相互作用的药物）可增强抗体依赖的细胞吞噬作用。ASPEN-06研究的2期部分纳入127例经治的HER2过表达晚期胃/胃食管结合部癌患者，随机接受Evorpacept联合曲妥珠单抗、雷莫西尤单抗和紫杉醇，或单纯三药方案。结果显示联合组客观缓解率在意向治疗人群为40.3%比26.6%，在新鲜活检HER2阳性亚组为54.8%比23.1%，差值超过预设阈值；但未达到与历史基准30%比较的统计学标准。联合组血液学毒性更常见，总体安全性相似。该结果支持进一步研究，但尚未证明优于现有方案。
为什么推荐给您：新机制药物联合方案的随机2期阳性趋势，但主要终点未达统计学标准，属早期信号。
不需要生物学背景，多打比方
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摘要Abstract
Evorpacept blocks the CD47-signal regulatory protein α interaction, enhancing antibody-dependent cellular phagocytosis. In the phase 2 portion of ASPEN-06 (a multicenter, open-label, randomized phase 2/3 study), 127 patients with pretreated, human epidermal growth factor receptor 2 (HER2)-overexpressing, advanced gastric/gastroesophageal junction cancer were randomized to evorpacept plus trastuzumab, ramucirumab and paclitaxel (evo + TRP; n = 63; fresh HER2+ biopsy, n = 22) or TRP alone (n = 64; fresh HER2+ biopsy, n = 26). The primary end point was investigator-assessed objective response rate (ORR). The primary analysis of ORR was designed to evaluate an ORR exceeding the historical 30% benchmark (ramucirumab/paclitaxel) (80% power for intent to treat (ITT) and 50% power for the ITT subpopulation (HER2 overexpression based on a post-trastuzumab 'fresh' biopsy)) and an improvement of ≥8.0% and ≥9.7% versus TRP in the ITT and ITT subpopulations, respectively. Key secondary end points included ORR by blinded independent central review, duration of response and progression-free survival by investigator or blinded independent central review, overall survival and safety. Post hoc biomarker analyses, including the assessment of the association of treatment efficacy with retained HER2 status (defined by HER2 positivity on fresh tumor biopsy or amplification in circulating tumor DNA analysis) and CD47 expression in tumor samples, were conducted. The investigator-assessed ORRs were 40.3% (evo + TRP) versus 26.6% (TRP) in the ITT population and 54.8% versus 23.1% in the fresh biopsy HER2+ subgroup. ORR differences (13.7% and 31.7%) exceeded the prespecified thresholds in both the ITT population and fresh biopsy HER2+ subgroup, meeting one of the two primary objectives; however, compared to the historical benchmark (30%), ORRs in the ITT population (40.3%; P = 0.0949, one-sided) and fresh biopsy HER2+ subgroup (54.8%; P = 0.030, one-sided) did not meet the prespecified statistical criterion (one-sided α = 0.025). While hematologic toxicities were more common with evo + TRP, overall safety was similar. In summary, evo + TRP showed encouraging efficacy with manageable safety in advanced gastric/gastroesophageal junction cancer. ClinicalTrials.gov identifier: NCT05002127 .