Authors: Liangjun Zhu, Sheng Li, Jun Bao, Xiaoyou Li, Quanliang Yang, Junying Xu, Surong Chen, Ge Feng, Chao Gao, Lin Feng, Bin Lu, Min Miao, Xinchu Ni, Guofang Wang, Lei Yang
Published: 2023-01-24
DOI: 10.1200/jco.2023.41.4_suppl.356
Source: Full article
356 Background: The combination of PD-1 and HER2 blockades showed potential benefit for patients with HER2-positive gastric cancer. This study aimed to investigate the safety and efficacy of camrelizumab plus pyrotinib and chemotherapy in the first-line setting for HER2-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Methods: This phase I, open-label, clinical trial (ChiCTR2000029717) included dose-escalation and dose-expansion cohorts. Patients aged 18 or older with HER2-positive G/GEJ cancer were enrolled. In dose-escalation phase, patients were administrated with three-week cycle of oral pyrotinib 240mg, 320mg or 400mg daily, intravenous camrelizumab 200mg and oxaliplatin 130mg/m2 on day 1, and oral capecitabine 1000mg/m2 twice a day for two weeks followed by one week off until unacceptable toxicities, progressive disease or death. Additional patients were enrolled in a dose-expansion phase and received maximum tolerated dose determined in the dose-escalation cohort. The primary endpoints were the safety and objective response rate (Response Evaluation Criteria in Solid Tumors version 1.1). Results: Between June, 2020 and June, 2022, a total of 31 patients were enrolled, with 9 patients in the dose-escalation phase (three patients received pyrotinib 240mg, 320mg or 400mg each) and 22 in the dose-expansion phase. During dose-escalation, five patients experienced six dose-limiting toxicity, including diarrhea (n=4), vomiting (n=1) and decreased appetite (n=1). The maximum tolerated dose of pyrotinib was 320 mg, which was chosen for dose-expansion. For 25 patients received pyrotinib 320 mg, 13 (52.0%) developed grade 3 or higher adverse events (AEs), and 6 (24.0%) discontinued treatment due to AE. The most common AE of any grade was diarrhea (96.0%), followed by vomiting (60.0%), decreased appetite (56.0%) and anemia (56.0%). The objective response rate and disease control rate were 96.0% and 100%, respectively. The 12-month progression-free survival rate and overall survival rate were 77.1% and 89.3%, respectively. Conclusions: Camrelizumab plus pyrotinib and chemotherapy showed promising efficacy in the first-line treatment of HER2-positive G/GEJ cancer, with acceptable safety profiles. The study is ongoing. Clinical trial information: ChiCTR2000029717 .[Table: see text]