Anlotinib Plus Toripalimab as First-line Treatment for Advanced Gastric Cancer With ECOG 2 (APICAL-GC)

Efficacy and Safety of Anlotinib Plus Toripalimab as First-line Regimen in Frail Patients (ECOG 2) With Advanced Gastric Cancer (APICAL-GC): an Open-label, Single Arm, Phase II Trial

This study is designed to evaluate the efficacy and safety of the combination of Anlotinib wiht Toripalimab in advanced gastric cancer with ECOG 2 as first-line regimen.

Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. Toripalimab is a humanized immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death 1 (programmed death-1; PD-1), with potential immune checkpoint inhibitory and antineoplastic activities. In the present study, we design a single-arm, single center Phase II trial to evaluate the efficacy and safety of the combination of Anlotinib wiht Toripalimab in advanced gastric cancer with ECOG 2 as first-line treatment.

Inclusion Criteria:

• Histologically confirmed, UICC stage IV gastric cancer;
• no prior systematic anti-cancer treatment and relapse or metastases was occurred more than 12 months after adjuvant chemotherapy;
• at least one measurable lesion;
• received radiotherapy 3 weeks before recruitment, but the lesion undergoing radiotherapy could not be used to calculate clinical benefit using RECISET criteria;
• ECOG performance status 2;
• the main organ function to meet the following criteria: HB ≥ 90g / L, ANC ≥ 1.5 × 109 / L, PLT ≥ 80 × 109 / L,BIL <1.5 times the upper limit of normal (ULN), ALT and AST <2.5 × ULN and if liver metastases, BIL < 3 × ULN, ALT and AST <5 × ULN; Serum Cr ≤ 1.5 × ULN;
• Patient's written declaration of consent obtained;
• Estimated life expectancy > 3 months;

Exclusion Criteria:

• harboring HER2 positive including IHC 3+ or IHC 2+ with Fish positive;
• dMMR/MSI-H;
• Myocardial infarction, unstable angina pectoris, Grade III or IV heart failure (NYHA classification);
• have received anlotinib or other immune checkpoint inhibitor ;
• with known or clinically suspected brain metastases, autoimmune disease, organ transplantation ;
• severe wounds or surgery 4 weeks before recruitment;
• received glucocorticoid (more than 10mg prednisone ) and immunosuppressive agents;
• History of a second malignancy during the past 5 years before inclusion in the study or during participation in the study, with the exception of a dermal basal cell or squamous cell carcinoma or cervical carcinoma in situ, if these were treated curatively.
• pregnancy or breast feeding;
• absent or restricted legal capacity;
• a significant concomitant disease which, in the investigating physician's opinion, rules out the patient's participation in the study