First-line of camrelizumab plus pyrotinib and chemotherapy in HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma: A dose escalation and expansion phase I study.

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/m 2 on day 1, and oral capecitabine 1000mg/m 2 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]