ARTEMIDE-Gastric01: A phase 3 randomized study of rilvegostomig with fluoropyrimidine and trastuzumab deruxtecan (T-DXd) as first-line (1L) treatment for locally advanced or metastatic HER2-positive gastric or gastroesophageal junction cancer (GC/GEJC).
Year: 2025
Type: conference-abstract
Abstract: TPS4204 Background: Patients with GC/GEJC often present with advanced disease, and prognosis for these patients is poor, with a 5-year relative survival rate of ~5%, highlighting a need for new treatment options. HER2 overexpression/amplification occurs in ~20% of cases. Adding immune checkpoint inhibition to trastuzumab (anti-HER2 monoclonal antibody) and chemotherapy has shown clinical benefit in patients with advanced HER2-positive GC/GEJC (Janjigian YY, et al. N Engl J Med 2024), and led to the approval of pembrolizumab (programmed cell death-1 [PD-1] inhibitor), trastuzumab, and chemotherapy for HER2-positive GC/GEJC with programmed cell death ligand-1 combined positive score (PD-L1 CPS) ≥1. T-DXd (a HER2-directed antibody-drug conjugate) is approved for the treatment of patients with locally advanced/metastatic HER2-positive GC/GEJC who have received a prior trastuzumab-based regimen. In addition, dual inhibition of PD-1 or PD-L1 and the immune checkpoint T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) has shown encouraging results across multiple tumor types, without major increases in high-grade toxicity compared with PD-1 or PD-L1 inhibition alone. Rilvegostomig is a monovalent, bispecific, humanized IgG1 monoclonal antibody targeting both PD-1 and TIGIT receptors that has shown encouraging efficacy with manageable safety as monotherapy in non-small-cell lung cancer (Hiltermann TJN, et al. WCLC 2024. Oral presentation 1751) and with chemotherapy in HER2-negative GC/GEJC (Herrero FR, et al. Ann Oncol 2024. Abs 1422P). Methods: ARTEMIDE-Gastric01 (NCT06764875) is a phase 3, randomized, open-label, sponsor-blinded, multicenter, global study that will assess the efficacy and safety of rilvegostomig with T-DXd and chemotherapy as 1L treatment in HER2-positive GC/GEJC with PD-L1 CPS ≥1. Approximately 840 participants (pts) will be randomized to Arm A: rilvegostomig + T-DXd + investigator’s (INV) choice of capecitabine or 5-fluorouracil (5-FU); Arm B: pembrolizumab + trastuzumab + INV choice of 5-FU and cisplatin (FP) or capecitabine and oxaliplatin (CAPOX); Arm C: rilvegostomig + trastuzumab + INV choice of FP or CAPOX. Eligible pts will have previously untreated, unresectable, histologically confirmed, locally advanced/metastatic HER2-positive and PD-L1 CPS ≥1 GC/GEJC and an ECOG performance status of 0 or 1. Dual-primary endpoints are progression-free survival (RECIST v1.1; blinded independent central review) and overall survival in all randomized pts. Secondary endpoints include safety/tolerability, objective response rate, and duration of response. Enrollment is planned across ~25 countries in Asia, Australia, Europe, and North and South America. Clinical trial information: NCT06764875 .
Source: Journal of Clinical Oncology
Institutions: Sun Yat-sen University, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Hospital Israelita Albert Einstein, Chang Gung University, Linkou Chang Gung Memorial Hospital, University Hospital Leipzig, Leipzig University, Yonsei University Health System, Yonsei Cancer Hospital, Universitat de Vic - Universitat Central de Catalunya, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, The Cancer Institute Hospital, Japanese Foundation For Cancer Research, Shanghai Jiao Tong University, Ruijin Hospital, AstraZeneca (United Kingdom), AstraZeneca (United States), Weill Cornell Medicine
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410815653