This study is designed to compare the efficacy and safety of KN026 combined chemotherapy with or without Enlonstobart versus Trastuzumab combined chemotherapy with or without Pembrolizumab as first-line treatment in HER2-positive unresectable locally advanced or metastatic gastric cancer.
Histologically or cytologically confirmed diagnosis of gastric cancer.
Participants unresectable locally advanced or metastatic gastric cancer who had not received systemic treatment (participants who had progressed 6 months after prior neoadjuvant/adjuvant therapy could be enrolled).
Confirmed to be HER2 positive (HER2-positive is defined as IHC 3+ or IHC 2+ with ISH positive) and PD-L1 status (participants of phase III should be confirmed by the pathology department of participating study center).
Phase II: Presence of at least 1 measurable lesion per RECIST 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Phase III:Presence of at least 1 evaluable lesion per RECIST 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Has received anti-tumor treatment such as systemic chemotherapy or other trial interventions within 28 days, or immunotherapy (e.g. interleukin, interferon, thymospipeptide, etc.), hormone therapy or targeted therapy within 14 days or 5 half-life (whichever is shorter) before randomization.
Participants with brain metastasis or spinal cord compression at screening (except for completed local treatment and discontinued glucocorticoids for at least 4 weeks before randomization , and stable central nervous system imaging and brain metastasis symptoms for at least 4 weeks).
Participants with PD-L1 CPS ≥1, who are receiving long-term immunotherapy (e.g., cyclosporine) or require daily systemic steroid therapy (e.g., >20 mg prednisone or equivalent), except those who treated with local glucocorticoids using nasal spray, inhalation, or other pathways.
Participants with PD-L1CPS ≥1, who have an active autoimmune disease or have a history of autoimmune disease 2 years before randomization and still require systemic treatment. However, participant with the following diseases is allowed to enroll: well-controlled type I diabetes, well-controlled hypothyroidism that requires hormone replacement therapy, skin diseases that do not require systemic treatment (such as vitiligo, psoriasis, or hair loss), or participant who is expected to not recur without external triggers.