1474TiP - A randomized phase II study of disitamab vedotin (DV) plus toripalimab and chemotherapy versus DV plus toripalimab versus chemotherapy as perioperative treatment for HER2-expressing locally advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJ)

Background

Gastric cancer is one of the most common malignancies worldwide. Despite of perioperative chemotherapy strategies, 5-year overall survival rates remains low. The addition of programmed cell death 1 (PD-1) inhibitors or targeted drugs also failed to prolong survival. DV, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E (MMAE) via a cleavable linker. Preliminary data indicated that DV combined with PD-1 inhibitor (toripalimab) has potential benefit in both HER2 positive (IHC 2+/FISH+, IHC 3+) and HER2 low (IHC 1+, IHC 2+/FISH-) advanced or metastatic GC patients. We aimed to evaluate DV plus toripalimab with or without chemotherapy as perioperative treatment for HER2-expressing (IHC 1+, 2+ or 3+) resectable GC/GEJ.

Trial design

This is a multicenter, open-label, randomized phase 2 trial. Key eligibility criteria include participants with resectable GC/GEJ clinically staged as cT3-4aN+M0 and HER2-expression (IHC 1+, 2+ or 3+). Eligible participants will be randomized 1:1:1 to three cohorts. Cohort 1: XELOX (oxaliplatin 130mg/m² plus capecitabine 1000mg/m²) every 3 weeks (Q3W) plus DV 2.5mg/kg Q2W and toripalimab 3.0mg/kg Q2W, cohort 2: DV Q2W plus toripalimab Q2W, cohort 3: XELOX Q3W. Neoadjuvant therapy will be administrated for 12 weeks, followed by surgical resection. Patients who have complete R0 resection will receive adjuvant therapy for 1 year (12 weeks for combination therapy, toripalimab will be administrated at most 1 year) in cohort 1 and 2, or 12 weeks in cohort 3. The primary endpoint is pCR rate by central pathological review, key secondary endpoints include R0 resection rate, major pathological response (MPR), event free survival (EFS) and safety. This trial began in November 2023 and has enrolled 29 patients at the time of submission.

Clinical trial identification

NCT06155383.

Editorial acknowledgement

Legal entity responsible for the study

RemeGen Co., Ltd.

Funding

RemeGen Co., Ltd.

Disclosure

J. Fang: Financial Interests, Personal and Institutional, Leadership Role: Remegen Co., Ltd. All other authors have declared no conflicts of interest.