2026-09-30 国立がん研究センター
図1A. エボルパセプト、トラスツズマブ、ラムシルマブ、パクリタキセル併用療法による抗腫瘍効果
＜関連情報＞
- https://www.ncc.go.jp/jp/information/researchtopics/2026/0930/index.html
- https://www.nature.com/articles/s41591-026-04700-3
HER2陽性胃癌におけるエボルパセプト＋トラスツズマブ、ラムシルマブ、パクリタキセル併用療法：ランダム化第2相試験 Evorpacept plus trastuzumab, ramucirumab and paclitaxel in HER2-positive gastric cancer: a randomized phase 2 trial
Kohei Shitara, Zev Wainberg, Josep Tabernero, Eric Van Cutsem, Clélia Coutzac, Christelle De La Fouchardière, Jeeyun Lee, Sun Young Rha, Yoon-Koo Kang, Philip Fanning, Alison Forgie, Cherry Mao, Daniel Brickman, Jaume Pons, Athanasios C. Tsiatis, Sophia Randolph & Keun-Wook Lee
Nature Medicine Published:24 September 2026
DOI:https://doi.org/10.1038/s41591-026-04700-3
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.
