Synergistic Effects of PD-1 Antibody and Chemotherapy Followed by Surgery-centric Local Treatment in Patients with Limited-metastatic Gastric or Gastroesophageal Adenocarcinoma (ROSETTE Trial): an Open-label, Single-center, Randomized Phase 2 Trial
ROSETTE trial is an open-label, randomized phase II study designed to investigate treatment strategies for patients with limited metastatic gastric or gastroesophageal adenocarcinoma. Eligible patients are randomized to receive either systemic treatment followed by surgeon-led local treatment, or systemic treatment alone. Systemic treatment combines immunotherapy with chemotherapy, while the surgeon-led local treatment utilizes a surgery-centric, multi-modality approach involving resection of both primary and metastatic tumors where feasible. For unresected or unresectable metastatic lesions, alternative local therapies are provided. The primary endpoint is the 1-year event-free survival (EFS) rate. Secondary endpoints include objective response rate (ORR), disease control rate (DCR), extended EFS, overall survival (OS), pathologic complete response rate (pCR), major pathologic response rate (MPR), and R0 resection rate.
• Men or women aged 18-79.
• Pathologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma (Siewert II or III only) with known PD-L1 expression status.
• HER2-negative gastric cancer, confirmed by HER2 immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
• Gastric cancer with proficient mismatch repair (pMMR) or microsatellite stability (MSS) as determined by immunohistochemistry or NCI-recommended microsatellite markers.
• Primary gastric cancer lesions are resectable, with limited distant metastases meeting the either of the following criteria: (1) condition (a) only; (2) any single condition from (b), with or without (a).
• (a) Non-regional intra-abdominal lymph node metastasis: Include metastasis to the superior mesenteric artery, middle colic artery, and para-aortic/retroperitoneal nodes (according to AJCC 8th edition standards) (21).
• (b1) Localized peritoneal metastasis: P0CY1, P1a, or P1b, according to the Japanese Classification of Gastric Carcinoma (15th edition) (22).
• (b2) Liver metastasis: Up to 5 metastatic lesions. (b3) Lung metastasis: Up to 5 unilateral metastatic lesions. (b4) Ovarian metastasis: Unilateral or bilateral. (b5) Adrenal metastasis: Unilateral or bilateral. (b6) Single-region extra-abdominal lymph node metastasis: Such as cervical, supraclavicular, or mediastinal lymph nodes.
• (b7) Bone metastasis limited to a single radiation field. (b8) Other limited metastases as determined by the research team.
• No previous anti-tumor treatments.
• ECOG score ≤2, no surgical contraindications.
• Life expectancy ≥ 3 months.
• Physical condition and organ function suitable for major abdominal surgery.
⁃ Willingness and ability to comply with the study protocol.
⁃ Fertile women with a negative urine or serum pregnancy test and agreement to use effective contraception during the study and for 180 days after the last dose. Non-sterilized men must also agree to use effective contraception.
⁃ Signed informed consent with an understanding that patients can withdraw anytime.