a study of hg381 administered to patients with advanced solid tumors

Conditions: Advanced Solid Tumor

Summary: this is a phase i, first in human, open-label, non-randomized, multicenter study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, preliminary efficacy and establish a recommended dose of hg381 administered intravenously (iv) alone in subjects with advanced solid tumors.

the trial consists of a dose escalation phase and a cohort expansion phase.in dose escalation phase, escalating doses of hg381 will be evaluated as guided by the traditional 3+3 design . in cohort expansion phase, subjects will receive hg381 alone at a single dose level determined based on the data form dose escalation phase. in total, approximately 57 subjects will participate in the study, approximately 42 in the dose-escalation cohort, and approximately 15 in the expansion cohort.

Eligibility criteria:
inclusion criteria: * capable of giving signed informed consent. * life expectancy of at least 3 months. * histological or cytological documentation of an advanced solid tumor，subjects with advanced/recurrent solid tumors, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established. * measurable disease per recist version 1.1, there is at least one measurable lesion during the screening period. * eastern cooperative oncology group (ecog) performance status (ps) 0-1. * adequate organ function : hematologic system: hemoglobin ≥9 g/dl, absolute neutrophil count \[anc\] ≥1.5x10\^9/l, platelets ≥100x10\^9/l, inr ≤ 1.5 and aptt ≤1.5 x uln; hepatic system: total bilirubin ≤1.5 x uln, alt and ast ≤ 2.5 x uln; renal system: serum creatinine ≤1.5×uln or creatinine clearance ≥50 ml/min (calculated by the cockcroft-gault formula); cardiac system: left ventricular ejection fraction (lvef) ≥50% ; qt interval (qtcf) ≤470 ms for women, and ≤450 ms for men; endocrine system: thyroid-stimulating hormone (tsh) is within the normal limits. * subjects with fertility must agree to take medically approved effective contraceptive measures during the entire trial period and at least 3 months after the last medication. exclusion criteria: * chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy and other anticancer therapy within 4 weeks. * concurrent medical condition requiring the use of other systemic immunosuppressive treatment within 4 weeks before the first dose of study treatment. * receipt of any live vaccine within 4 weeks of the start of study treatment. * receipt of unmarketed clinical trial drugs or treatments within 4 weeks of the start of study treatment. * receipt of surgery or interventional treatment (excluding tumor biopsy, puncture, etc.) within 4 weeks of the start of study treatment. * history or evidence of cardiovascular and cerebrovascular diseases risk. * subjects with uncontrolled diabetes. * symptomatic central nervous system (cns) metastases or asymptomatic cns metastases that have required steroids within 2 weeks prior to first dose of study treatment. * currently or in the past suffering from malignant tumors. * uncontrollable pleural effusion, pericardial effusion or ascites still need to be drained frequently after appropriate intervention. * active or suspected autoimmune disease. * history of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia, or evidence of active, non-infectious pneumonitis. * toxicity from previous treatment including: toxicity grade ≥3 related to prior immunotherapy and that led to study treatment discontinuation; toxicity related to prior treatment that has not resolved to grade ≤ 1. * subjects who have acute bacterial, viral or fungal infections and require systemic anti-infective treatment. * positive test for syphilis antibodies or human immunodeficiency virus (hiv) antibodies. * subjects who are allergic to test drugs and excipients. * women who are pregnant or breastfeeding. * known drug or alcohol abuse. * patients with mental or neurological diseases. * prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation. * subjects who have a history of serious systemic disease or any other reason are not suitable to participate in this trial as judged by the investigator.