Paclitaxel, Ramucirumab and Tislelizumab Switch Maintenance in Advanced HER2-negative and PD-L1 TAP Score of 5 or More Advanced Gastroesophageal Adenocarcinoma

ARMANI-2/ENGIC8 is a randomized, open-label, phase III trial evaluating a switch maintenance strategy in patients with previously untreated, locally advanced unresectable or metastatic, HER2-negative and PD-L1-positive gastroesophageal adenocarcinoma. The combination of platinum- and fluoropyrimidine-based chemotherapy with an anti-PD-1 agent represents a first-line treatment option for patients with advanced HER2-negative, PD-L1-positive gastroesophageal adenocarcinoma. However, disease progression remains frequent and may lead to clinical deterioration, preventing a substantial proportion of patients from receiving subsequent anticancer treatment. The phase III ARMANI trial demonstrated that, in patients with advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma who achieved disease control after 3 months of first-line oxaliplatin- and fluoropyrimidine-based chemotherapy, switching to paclitaxel plus ramucirumab significantly improved progression-free survival and overall survival compared with continuation of the initial chemotherapy. These findings support the early introduction of a non-cross-resistant treatment before the development of chemotherapy-resistant disease and clinical deterioration. ARMANI-2 builds on this strategy in the current immunotherapy-based treatment setting. In addition, VEGF/VEGFR blockade may have immunomodulatory effects that provide a biological rationale for combining ramucirumab with PD-1 blockade. All eligible patients will receive a 12-week induction treatment with tislelizumab combined with platinum- and fluoropyrimidine-based chemotherapy (mFOLFOX6, CAPOX, or cisplatin plus fluorouracil). Patients who complete induction without disease progression or permanent treatment discontinuation will be randomized 1:1 to receive either switch maintenance with paclitaxel, ramucirumab, and tislelizumab (Arm A) or continuation of the chemotherapy regimen used during induction in combination with tislelizumab (Arm B).