更新于：2024-11-01

HER2-Low Gastroesophageal Junction Cancer

HER2低表达胃食管交界处癌

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与 HER2低表达胃食管交界处癌相关的药物

Cinrebafusp alfa

靶点

4-1BB x HER2

作用机制

4-1BB激动剂 [+1]

在研机构

Pieris Pharmaceuticals, Inc.

原研机构

Pieris Pharmaceuticals, Inc.

在研适应症

HER2阳性胃食管结合部腺癌 [+5]

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 HER2低表达胃食管交界处癌相关的临床试验

JPRN-jRCT2031230477 / Recruiting临床1/2期IIT

An open label phase 1b/2 study to evaluate efficacy and safety of trastuzumab deruxtecan (T-DXd) plus nivolumab plus capecitabin plus oxaliplatin for patients with HER2 low gastric and gastroesophageal junction adenocarcinoma - T-DXd_HER2Low

开始日期2023-11-30

申办/合作机构-

NCT05894824 / Not yet recruiting临床1/2期IIT

An Open Label, Single-arm, Multicenter Phase Ib/II Study to Evaluate the Safety and Efficacy of T-Dxd in Combination With Ramucirumab as a 2nd Line in Patients With HER2 Low Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

This is a Phase Ib/II study to identify the RP2D of T-DXd combination with Ram and to assess the safety and clinical efficacy of this combined treatment in advanced gastric cancer after first-line treatment. The study will be conducted in two parts: Phase Ib dose escalation study to determine the MTD and RP2D of T-DXd combination and Ram, and Phase II to further evaluate the safety and tolerability of T-DXd combinations with Ram at the RP2D and determine anti-tumor activity.

开始日期2023-06-01

申办/合作机构

Yonsei University

NCT05190445 / Active, not recruiting临床2期

A Phase 2, Multi-Center, Open-Label Study of Cinrebafusp Alfa (PRS-343) in Combination With Ramucirumab and Paclitaxel in Patients With HER2-Positive Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma and in Combination With Tucatinib in Patients With HER2 Low Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

A Phase 2, multi-center, open-label study of cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxel in patients with HER2-high and in combination with tucatanib in patients with HER2-low gastric or gastroesophageal junction (GEJ) adenocarcinoma.

开始日期2021-11-01

申办/合作机构

Pieris Pharmaceuticals, Inc.

100 项与 HER2低表达胃食管交界处癌相关的临床结果

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100 项与 HER2低表达胃食管交界处癌相关的转化医学

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0 项与 HER2低表达胃食管交界处癌相关的专利（医药）

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项与 HER2低表达胃食管交界处癌相关的文献（医药）

2024-01-01·Frontiers in oncology

Complete response to disitamab vedotin in HER2-low metastatic endometrial carcinoma: a case report and review of the literature.

Article

作者: Mao, Jingjing ; Yang, Fujun ; Sun, Shanshan ; Zhou, Haoxing ; Feng, Hu ; Yang, Hongbo ; Bi, Shasha ; Li, Na

Endometrial cancer (EC) is one of the most common gynecologic malignancies with increasing morbidity. The prognosis for patients diagnosed with early-stage EC remains favorable; however, for patients with recurrent or metastatic EC, the prognosis is poor and treatment options, until recently, are limited. Antibody drug conjugates (ADCs) represent innovative strategies in cancer treatment; however, there are less investigations regarding their efficacy in EC. This report describes an EC case with low human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) expression score (IHC 2+) that experienced recurrent metastasis in the abdominal and peritoneal following post-surgical chemotherapy and radiotherapy. Subsequently, the commencement of HER2-targeted ADC, disitamab vedotin (RC48; 2.5 mg/kg), administered intravenously every two weeks, was initiated. The tumor lesions shrunk markedly after three cycles of treatment and disappeared by the completion of ten cycles of therapy. The patient is still in remission at present. The current findings imply the potential efficacy of HER2-targeted ADCs for patients with HER2-low metastatic EC.

2023-12-01·Journal of Clinical Pathology

HER2-low in gastro-oesophageal adenocarcinoma: a real-world pathological perspective

Article

作者: Battista, Serena ; Cassoni, Paola ; Grillo, Federica ; De Lisi, Giuseppe ; Ugolini, Clara ; Vanoli, Alessandro ; Angerilli, Valentina ; Campora, Michela ; Parente, Paola ; Fassan, Matteo ; Mastracci, Luca ; Cavallin, Francesco ; Gambella, Alessandro

AimsIn the DESTINY-Gastric01 trial, a novel HER2-targeted antibody-drug conjugate trastuzumab deruxtecan proved to be effective in HER2-low gastro-oesophageal adenocarcinomas. The aim of our study is to investigate the clinicopathological and molecular features of HER2-low gastric/gastro-oesophageal junction cancers in the real-world setting of a large multi-Institutional series.MethodsWe retrospectively evaluated 1210 formalin-fixed paraffin-embedded samples of gastro-oesophageal adenocarcinomas which were analysed by immunohistochemistry for HER2 protein expression in 8 Italian surgical pathology units from January 2018 to June 2022. We assessed the prevalence of HER2-low (ie, HER2 1+ and HER2 2+ without amplification) and its correlation with clinical and histopathological features, other biomarkers’ status, including mismatch repair/microsatellite instability status, Epstein-Barr encoding region (EBER) and PD-L1 Combined Positive Score.ResultsHER2 status could be assessed in 1189/1210 cases, including 710 HER2 0 cases, 217 HER2 1+, 120 not amplified HER2 2+, 41 amplified HER2 2+ and 101 HER2 3+. The estimated prevalence of HER2-low was 28.3% (95% CI 25.8% to 31.0%) overall, and was higher in biopsy specimens (34.9%, 95% CI 31.2% to 38.8%) compared with surgical resection specimens (21.0%, 95% CI 17.7% to 24.6%) (p<0.0001). Moreover, HER2-low prevalence ranged from 19.1% to 40.6% among centres (p=0.0005).ConclusionsThis work shows how the expansion of the HER2 spectrum might raise problems in reproducibility, especially in biopsy specimens, decreasing interlaboratory and interobserver concordance. If controlled trials confirm the promising activity of novel anti-HER2 agents in HER2-low gastro-oesophageal cancers, a shift in the interpretation of HER2 status may need to be pursued.

2023-08-01·ESMO Open

Incidence, clinicopathological features, and clinical outcomes of low HER2 expressed, inoperable, advanced, or recurrent gastric/gastroesophageal junction adenocarcinoma

Article

作者: Shinozaki, E ; Ooki, A ; Yamamoto, N ; Takahari, D ; Ogura, M ; Chin, K ; Fukuda, K ; Osumi, H ; Wakatsuki, T ; Takamatsu, M ; Nakayama, I ; Fukuoka, S ; Yamaguchi, K

BACKGROUNDAccording to the DESTINY-Breast04 trial, treating patients with breast cancer and low human epidermal growth factor receptor 2 expressions (HER2-low) varies from that of those with no HER2 expression. However, it is interesting to know if HER2-low indicates for anti-HER2 therapy in the gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Hence we conducted this study to assess the incidence, clinicopathological features, and treatment outcomes of patients with HER2-low G/GEJ adenocarcinoma.PATIENTS AND METHODSThis was a single-center, retrospective observational study. Patients with previously untreated G/GEJ adenocarcinoma were classified based on their HER2 status using immunohistochemistry (IHC) with or without in situ hybridization (ISH) as follows: HER2 negative (IHC 0), HER2-low (IHC 1+ or 2+/ISH-), and HER2-positive (IHC2+/ISH+ or 3+).RESULTSIn total, 734 patients with G/GEJ adenocarcinoma were divided into three groups (HER2-negative, n = 410; HER2-low, n = 154, and HER2-positive, n = 170). The intestinal-type histology, peritoneal metastasis, and higher serum carcinoembryonic antigen (CEA) levels differed significantly among patients with negative, low, and positive HER2 statuses: intestinal-type histology (21.0%, 44.2%, and 59.8%, respectively), peritoneal metastasis (56.3%, 44.8%, and 21.8%, respectively), and higher serum CEA level (32.2%, 41.6%, and 56.5%, respectively). Improved survival was observed in the HER2-positive group than in the HER2-negative G/GEJ adenocarcinoma group [hazard ratio (HR) = 0.73, 95% confidence interval (CI) 0.59-0.89; P = 0.002]. However, the prognoses of the HER2-low and HER2-negative groups were similar (HR = 1.01, 95% CI 0.82-1.23; P = 0.843).CONCLUSIONSPatients with HER2-low G/GEJ adenocarcinoma exhibited intermediate and distinct characteristics than those in the HER2-negative group. Similarly, the HER2-low group's prognosis was worse than that of the HER2-positive group. Therefore developing novel therapeutic strategies targeting HER2-low G/GEJ adenocarcinoma is required.