Efficacy and safety of perioperative chemotherapy combined with tislelizumab and trastuzumab for HER2-positive resectable gastric/gastroesophageal junction cancer (GC/EGJC): Preliminary results of a phase 2, single-arm trial.

person Chunlin Zhao First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China info_outline Chunlin Zhao, Xiangrui Meng, Zhengzheng Shan, Jianwu Jiang, Xinyu Liu, Haohao Li, Junfeng Sun, Chaohui Ding, Jin Xia, Zhiqiang Liu, Feng Wang

Authors person Chunlin Zhao First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China info_outline Chunlin Zhao, Xiangrui Meng, Zhengzheng Shan, Jianwu Jiang, Xinyu Liu, Haohao Li, Junfeng Sun, Chaohui Ding, Jin Xia, Zhiqiang Liu, Feng Wang Organizations First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China, Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, Anyang Tumor Hospital, Anyang, Henan, China Abstract Disclosures Research Funding No funding received None. Background: Recently, immunotherapy combined with trastuzumab and chemotherapy have been recommended by the clinical guidelines of many countries as the first-line treatment for advanced HER2-positive G/GEJ adenocarcinoma. Combining chemotherapy with tislelizumab and trastuzumab in the neoadjuvant/adjuvant setting may benefit patients with locally advanced, resectable HER2-positive GC/GEJC. Methods: This study is a multicenter, single-arm, open-label phase 2 study (NCT04819971). Patients with histologically confirmed cT2-4NxM0 or cTxN+M0, (TNM 8th edition), resectable gastric adenocarcinoma are eligible for this study. Neoadjuvant therapy will be administered for four cycles. The patients will receive tislelizumab and trastuzumab for 1 cycle (Q3W), followed by tislelizumab and trastuzumab combined with DOS (Docetaxel + Oxaliplatin + S-1) for 3 cycles (Q3W). Surgery is planned 4-6 weeks after preoperative treatment. Patients who have complete surgical resection will receive adjuvant therapy starting within 4–6 weeks after surgery for 6 cycles (three cycles of tislelizumab and trastuzumab combined with DOS regimen, followed by 6 weeks of tislelizumab and trastuzumab for 6 cycles. The primary endpoint was pathological complete response rate (pCR). Secondary endpoints included R0 resection rate, 1-year and 2-year event-free survival (EFS), overall survival (OS) and safety. Results: From September 13, 2021 to February 01, 2023, 12 patients were enrolled (58.0% male, median age 61 years old), and the median follow up time was 7.3 months (0.4-16.9). Seven patients completed surgery, and 5 patients were undergoing neoadjuvant therapy. The R0 resection rate was 100%, 3 patients (42.9%) achieved pCR, and 4 patients (57.1%) achieved major pathological remission (MPR). Postoperative pathology showed tumor downstaging in 5 cases after neoadjuvant therapy, with a decrease rate of 71.4%. Median OS and EFS have not been reached. The most common AEs (all grades, grade ≥3) were anemia in 1 (8.3%) and neutropenia in 1 case (8.3%). The immune-related adverse events were all grade 1 included 2 thyroid dysfunction (16.7%), 1 abnormal liver function (8.3%), and 1 of elevated blood sugar (8.3%). No grade 3 or higher immune-related AE was observed. No treatment related deaths were reported. Conclusions: According to the preliminary results, tislelizumab combined with trastuzumab and standard chemotherapy in the perioperative period of HER2-positive GC and EGJ have a good clinical benefit trend and controllable security. Clinical trial information: NCT04819971.

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