. 2020 Nov 10;17(5):491–501. doi: 10.2217/fon-2020-0737

Table 2. . Eligibility criteria.

Inclusion criteria	Exclusion criteria
• Male or female • Age ≥18 years • Previously untreated histologically or cytologically confirmed locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma • HER2-positive disease, defined as either IHC 3+ or IHC 2+ in combination with ISH+ (or FISH), as assessed by BICR on primary or metastatic tumor • Measurable disease per RECIST v1.1 by site investigator • Willing to use adequate contraception methods throughout the study and for 7 months after the last dose of study treatment • ECOG PS 0 or 1 • Life expectancy ≥6 months • Willing to provide a tumor tissue sample adequate for PD-L1 and MSI biomarker analysis • Adequate cardiac function, defined as left ventricular ejection fraction ≥55% as determined by MUGA scan or ECHO and QT interval calculated according to the Fridericia method (≤470 ms for men and ≤480 ms for women) • Adequate hematologic function, defined as ANC ≥1500/μl, platelet count ≥100,000/μl and hemoglobin ≥9.0 g/dl or ≥5.6 mmol/l • Adequate renal function, defined as creatinine ≤1.5 × ULN or measured or calculated creatinine clearance ≥60 ml/min for those with creatinine levels 1.5 × ULN • Adequate hepatic function, defined as total bilirubin ≤1.5 × ULN or direct bilirubin ≤ULN for those with total bilirubin levels >1.5 × ULN, ALT/AST levels ≤2.5 × ULN or ≤5 × ULN for those with liver metastases, and albumin ≥2.5 g/dl • Adequate coagulation function, defined as INR ≤1.5 × ULN, unless the patient is receiving anticoagulant therapy with PT or aPTT/PTT is within the therapeutic range • Written informed consent	• Previously received neoadjuvant or adjuvant therapy for locally advanced or metastatic disease (as long as it was completed ≥6 months before randomization without disease progression) • Major surgery, open biopsy or significant traumatic injury ≤28 days before randomization, or anticipated need for major surgery during the study treatment period • Radiotherapy ≤14 days of randomization • Known additional malignancy that is progressing or has necessitated active treatment within the past 5 years (except BCC or SCC of the skin that has undergone potentially curative treatment or in situ cervical cancer) • Known active CNS metastases and/or carcinomatous meningitis (patients with previously treated brain metastases may be eligible if disease is radiologically and clinically stable) • Active autoimmune disease that has necessitated systemic treatment (other than replacement therapy) in the past 2 years • Diagnosis of immunodeficiency or receiving long-term systemic steroid therapy (≥10 mg/day prednisone equivalent) or any other form of immunosuppression therapy within 7 days before the first dose of study treatment • History of (noninfectious) pneumonitis treated with steroids or current pneumonitis • History of active tuberculosis • Active infection necessitating systemic therapy • Poorly controlled diarrhea • Accumulation of pleural, ascitic or pericardial fluid necessitating drainage or diuretic drugs ≤2 weeks before enrollment • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the study results or interfere with study participation • Peripheral neuropathy grade >1 • Psychiatric or substance abuse disorder that could impede cooperation with study requirements • Positive urine pregnancy test ≤72 h before randomization (females of childbearing potential) • Pregnant or breastfeeding or expecting to conceive or father children within the projected study duration • Active or clinically significant cardiac disease • Known history of HIV, HBV or HCV infection • Known hypersensitivity (grade ≥3) to any of the study drugs or their excipients • Active infection necessitating systemic therapy • Allogeneic tissue or solid organ transplant • Previous treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA4, OX40, CD137) • Immunized with live vaccine ≤30 days before first dose of study treatment • Participation in study of investigational agent or device ≤4 weeks before the first dose of study treatment

Inclusion criteria

Exclusion criteria

• Male or female
• Age ≥18 years
• Previously untreated histologically or cytologically confirmed locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma
• HER2-positive disease, defined as either IHC 3+ or IHC 2+ in combination with ISH+ (or FISH), as assessed by BICR on primary or metastatic tumor
• Measurable disease per RECIST v1.1 by site investigator
• Willing to use adequate contraception methods throughout the study and for 7 months after the last dose of study treatment
• ECOG PS 0 or 1
• Life expectancy ≥6 months
• Willing to provide a tumor tissue sample adequate for PD-L1 and MSI biomarker analysis
• Adequate cardiac function, defined as left ventricular ejection fraction ≥55% as determined by MUGA scan or ECHO and QT interval calculated according to the Fridericia method (≤470 ms for men and ≤480 ms for women)
• Adequate hematologic function, defined as ANC ≥1500/μl, platelet count ≥100,000/μl and hemoglobin ≥9.0 g/dl or ≥5.6 mmol/l
• Adequate renal function, defined as creatinine ≤1.5 × ULN or measured or calculated creatinine clearance ≥60 ml/min for those with creatinine levels 1.5 × ULN
• Adequate hepatic function, defined as total bilirubin ≤1.5 × ULN or direct bilirubin ≤ULN for those with total bilirubin levels >1.5 × ULN, ALT/AST levels ≤2.5 × ULN or ≤5 × ULN for those with liver metastases, and albumin ≥2.5 g/dl
• Adequate coagulation function, defined as INR ≤1.5 × ULN, unless the patient is receiving anticoagulant therapy with PT or aPTT/PTT is within the therapeutic range
• Written informed consent

• Previously received neoadjuvant or adjuvant therapy for locally advanced or metastatic disease (as long as it was completed ≥6 months before randomization without disease progression)
• Major surgery, open biopsy or significant traumatic injury ≤28 days before randomization, or anticipated need for major surgery during the study treatment period
• Radiotherapy ≤14 days of randomization
• Known additional malignancy that is progressing or has necessitated active treatment within the past 5 years (except BCC or SCC of the skin that has undergone potentially curative treatment or in situ cervical cancer)
• Known active CNS metastases and/or carcinomatous meningitis (patients with previously treated brain metastases may be eligible if disease is radiologically and clinically stable)
• Active autoimmune disease that has necessitated systemic treatment (other than replacement therapy) in the past 2 years
• Diagnosis of immunodeficiency or receiving long-term systemic steroid therapy (≥10 mg/day prednisone equivalent) or any other form of immunosuppression therapy within 7 days before the first dose of study treatment
• History of (noninfectious) pneumonitis treated with steroids or current pneumonitis
• History of active tuberculosis
• Active infection necessitating systemic therapy
• Poorly controlled diarrhea
• Accumulation of pleural, ascitic or pericardial fluid necessitating drainage or diuretic drugs ≤2 weeks before enrollment
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the study results or interfere with study participation
• Peripheral neuropathy grade >1
• Psychiatric or substance abuse disorder that could impede cooperation with study requirements
• Positive urine pregnancy test ≤72 h before randomization (females of childbearing potential)
• Pregnant or breastfeeding or expecting to conceive or father children within the projected study duration
• Active or clinically significant cardiac disease
• Known history of HIV, HBV or HCV infection
• Known hypersensitivity (grade ≥3) to any of the study drugs or their excipients
• Active infection necessitating systemic therapy
• Allogeneic tissue or solid organ transplant
• Previous treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA4, OX40, CD137)
• Immunized with live vaccine ≤30 days before first dose of study treatment
• Participation in study of investigational agent or device ≤4 weeks before the first dose of study treatment

ANC: Absolute neutrophil count; aPTT: Activated partial thromboplastin time; BCC: Basal cell carcinoma; BICR: Blinded-independent central review; CNS: Central nervous system; ECHO: Echocardiogram; ECOG: Eastern Cooperative Oncology Group; FISH: Fluorescent in-situ hybridization; GEJ: Gastroesophageal junction; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; IHC: Immunohistochemistry; INR: International normalized ratio; ISH: In-situ hybridization; MSI: Microsatellite instability; MUGA: Multigated acquisition; PT: Prothrombin time; PTT: Partial thromboplastin time; RECIST v1.1: Response Evaluation Criteria in Solid Tumors version 1.1; SCC: Squamous cell carcinoma; ULN: Upper limit of normal.