Ko Andrew H, Chao Joseph, Noel Marcus S, Shankaran Veena, Sohal Davendra, Crow Mary, Oberstein Paul E, Scott Aaron J, McRee Autumn J, Rocha Lima Caio Max Sao Pedro, Fong Lawrence, Keenan Bridget P, Soto Maira, Filbert Erin L, Hsu Frank J, Yang Xiaodong
Division of Hematology and Oncology, University of California San Francisco, San Francisco, California.
City of Hope Comprehensive Cancer Center, Duarte, California.
Cancer Res Commun. 2025 Feb 1;5(2):349-357. doi: 10.1158/2767-9764.CRC-24-0513.
Neoadjuvant chemoradiation (NCRT) followed by surgical resection represents a standard approach for patients with locally advanced esophageal/gastroesophageal junction (GEJ) cancers. Sotigalimab is a high-affinity CD40 agonist antibody capable of inducing and expanding antitumor immune responses by activating dendritic cells, T and B lymphocytes, NK cells, and M1 macrophages. This study examined the safety and efficacy of combining sotigalimab with NCRT in patients with esophageal or GEJ cancers.
Patients with resectable (T1-3 Nx) adenocarcinoma or squamous cell carcinoma of the esophagus or GEJ were eligible. T1N0 and cervical tumors were excluded. Study treatment: weekly carboplatin/paclitaxel with concurrent radiation 5,040 cGy plus 3 to 4 doses of sotigalimab prior to Ivor Lewis esophagectomy. Primary efficacy endpoint was the pathologic complete response (path CR) rate.
Thirty-three patients were enrolled (adenocarcinoma 76%, squamous cell carcinoma 24%; and clinical stage III 67%). Ninety percent of patients received all planned doses of sotigalimab. The most common adverse events attributed to sotigalimab were nausea, fever/chills, fatigue, and cytokine release syndrome; most of these were grade 1 to 2. Grade ≥3 cytokine release syndrome was observed in 3 patients (9%). Twenty-five of the 29 efficacy-evaluable patients underwent an R0 resection (87.9%), with an overall path CR rate of 37.9% (11/29). Post-tumor samples demonstrated increased infiltration and activation of dendritic cells, monocytes, and cytotoxic T cells compared with baseline.
Sotigalimab combined with NCRT for esophageal or GEJ cancers was generally well tolerated and achieved path CR rates that compare favorably with historical data and are promising for this treatment strategy. Clinical trial information: NCT03165994.
The current study represents the first report to evaluate a CD40 agonist antibody in combination with concurrent chemoradiation in the neoadjuvant setting for patients with esophageal/GEJ cancers. This novel strategy was both safe and feasible, producing encouraging path CR rates that compare favorably with historical data. Our findings support the further evaluation of how immune-based therapies may be incorporated into perioperative treatment paradigms for upper gastrointestinal malignancies.
新辅助放化疗（NCRT）后行手术切除是局部晚期食管癌/胃食管交界（GEJ）癌患者的标准治疗方法。索替吉利单抗是一种高亲和力的CD40激动剂抗体，能够通过激活树突状细胞、T和B淋巴细胞、NK细胞及M1巨噬细胞来诱导和扩大抗肿瘤免疫反应。本研究探讨了索替吉利单抗联合NCRT治疗食管癌或GEJ癌患者的安全性和疗效。
符合条件的患者为可切除（T1-3 Nx）的食管或GEJ腺癌或鳞状细胞癌患者。排除T1N0和宫颈肿瘤患者。研究治疗方案：在进行Ivor Lewis食管切除术之前，每周给予卡铂/紫杉醇并同时进行5040 cGy的放疗，外加3至4剂索替吉利单抗。主要疗效终点为病理完全缓解（path CR）率。
共纳入33例患者（腺癌占76%，鳞状细胞癌占24%；临床III期占67%）。90%的患者接受了所有计划剂量的索替吉利单抗。索替吉利单抗引起的最常见不良事件为恶心、发热/寒战、疲劳和细胞因子释放综合征；其中大多数为1至2级。3例患者（9%）出现≥3级细胞因子释放综合征。29例可评估疗效的患者中有25例接受了R0切除（87.9%），总体病理完全缓解率为37.9%（11/29）。与基线相比，肿瘤切除后的样本显示树突状细胞、单核细胞和细胞毒性T细胞的浸润及激活增加。
索替吉利单抗联合NCRT治疗食管癌或GEJ癌一般耐受性良好，病理完全缓解率与历史数据相比具有优势，该治疗策略前景可期。临床试验信息：NCT03165994。
本研究是首篇评估CD40激动剂抗体联合新辅助同步放化疗治疗食管癌/GEJ癌患者的报告。这种新策略安全可行，产生了令人鼓舞的病理完全缓解率，与历史数据相比具有优势。我们的研究结果支持进一步评估基于免疫的疗法如何纳入上消化道恶性肿瘤的围手术期治疗模式。
