A Phase Ia/Ib Study of IBI315 in Patients With HER2-expressing Advanced Solid Tumor

This phase Ia/Ib, open-label, multicenter study has two stages. The Ia stage is a dose-escalation study that will focus on safety, tolerability, efficacy and RP2D . Patients with HER2-expressing advanced solid tumor who failed from previous standard of care will be enrolled in the phase Ia study. DLT observation period is 28 days.

Inclusion criteria

• Written (signed) informed consent.
• Life expectancy ≥12 weeks.
• Patients with HER2-expressing advanced solid tumor who failed on current standard of care
• According to RECIST 1.1, at least one measurable lesion (radiation-naïve) exists.
• ECOG performance status 0-1.
• Adequate organ and marrow function evaluated by laboratory tests as follow:

• CBC: absolute neutrophil count (ANC) ≥ 1.0×109/L (Ia stage) or 1.5×109/L (Ib stage); Platelet (PLT) ≥ 75×109/L; Hemoglobin (HGB) ≥ 9.0g/L;
• Liver function: Total bilirubin (TBIL) ≤ 1.5×upper limit of normal value (ULN) for patients without hepatic metastases, ≤ 2×ULN for patients with hepatic metastases or Gilbert syndrome; Alanine aminotransferase (ALT) ≤ 2.5×ULN; Aspartate transferase (AST) ≤ 2.5×ULN;
• Renal function: Clearance of creatinine (CCr) by Cockcroft-Gault formula or 24-hour urine collection ≥ 50ml/min;
• Urinalysis: urine protein < 2+ or urine protein in 24-hour urine collection < 1g;
• Coagulation function: activated partial thromboplastin time (APTT）≤ 1.5×ULN; international normalized ratio (INR）≤ 1.5
• left ventricular ejection fraction (LVEF) ≥ 50% by echocardiography;
• Accumulative exposure to doxorubicin ≤ 360mg/m2; accumulative exposure to epirubicin ≤ 720mg/m2;
• Agree to use an approved contraceptive method during the treatment period, until 180 days after last dose of treatment.
• Post-menopause female subject or pre-menopause female with negative HCG level in urine or blood.

Exclusion criteria

• Any greater than NCI CTCAE 0/1 adverse event exists within 4 weeks before enrollment, not including hair loss and fatigue;
• Received major surgery or having unhealed wound, ulcer, or bone fracture;• Received whole pelvic radiation;
• Plan to receive any other anti-cancer therapy not specified in the protocol, except for palliative radiotherapy;
• CNS metastasis, spinal compression, or carcinomatous meningitis
• Active autoimmune disease or inflammatory disorders.
• Primary immunodeficiency diseases;
• Pregnant or breast-feeding female.