study of zg0895.hcl in patients with advanced solid tumors

Conditions: Advanced Solid Tumor

Summary: the primary objective of this study is to assess the tolerability and safety of zg0895.hcl, and to assess the maximum tolerated dose (mtd)/ recommended phase 2 dose (rp2d) of zg0895.hcl.


Eligibility criteria:
inclusion criteria: * fully understand the study and voluntarily sign the informed consent form(icf). * age ≥ 18 and ≤ 75 years old at the time of signing the icf, either male or female; * eastern cooperative oncology group (ecog) performance status of 0 or 1. * life expectancy ≥ 3 months. * all adverse events from prior treatment have either returned to baseline or ctcae 5.0 ≤ grade 1(except for aes not constituting a safety risk in the opinions of the investigators, e.g. alopecia, hypothyroidism which can be treated with a hormone replacement, etc). * both male and female participants (unless postmenopausal, surgical sterilization) and partners must agree to use a reliable form of contraception during the study treatment period and for at least 6 months after the last dose of the study drug. * for lesions that have received radiation therapy, only after the progression of the lesions, they can be considered measurable lesions. part 1: * must have at least 1 measurable lesion per response evaluation criteria in solid tumors v1.1 (recist v1.1). * participants with histologically or cytologically confirmed diagnosis of advanced solid tumors, in whom available standard treatments failed or were intolerable. exclusion criteria: * participants receiving any of the following treatments: 1. previously treated with systemic tlr7/8 immunomodulators. 2. any other investigational product treatment within 4 weeks before the first dosing. 3. chemotherapy, biotherapy, endocrine therapy (except for hormone replacement), and biological targeted medicines within 4 weeks before the first dosing. local palliative radiotherapy, traditional chinese medicine with anti-tumor effect, and small molecule targeted therapy within 2 weeks (or 5 half-lives, whichever is longer) before the first dosing. 4. major surgery within 4 weeks before the first dosing for any reason (excluding puncture biopsy), or need to undergo elective surgery during the trial. 5. potent cyp3a4/5 inducer or inhibitor within 2 weeks prior to administration of the first dose of the study drug. 6. systemic immunosuppressive drugs within 2 weeks prior to administration of the first dose of the study drug, including systemic corticosteroids (\>10 mg/day prednisone or equivalent). 7. other immunomodulators within 2 weeks prior to administration of the first dose of the study drug, including but not limited to thymosin, interleukin-2 and interferon. * had ctcae grade ≥3 immune-related adverse events (irae) after receiving immunotherapy. * the main organ function meets any of the following criteria within 7 days prior to the first dosing. （note: blood transfusion, epo, g-csf, albumin infusion and renal replacement therapy are not allowed within 14 days prior to treatment.) 1. hematological function: anc \< 1.5×10\^9/l, plt \< 75×10\^9/l, hemoglobin (hb) \< 100 g/l. 2. hepatic function: alanine aminotransferase (alt) and aspartate aminotransferase (ast) ≥ 3×uln; alt and ast ≥ 5×uln for participants with liver metastases; total bilirubin (tbil) ≥ 1.5×uln; albumin \< 30 g/l. 3. creatinine clearance\< 75 ml/min. 4. inr \> 1.5 or aptt \> 1.5×uln. 5. the urine protein presents positive and the quantitative result of 24-h urine protein ≥ 1 g. * participants with symptomatic central nervous system (cns) metastases or carcinomatous meningitis; or other evidence suggesting that the central nervous system metastasis or meningeal metastasis is not well-controlled and is judged by the investigator to be unsuitable for enrollment. * uncontrollable third cavity effusion (e.g. large amount pleural effusion, ascites, or pericardial effusion, etc.) requiring repeated drainage, which is judged by the investigator to be unsuitable for enrollment. * known history of neurological disorders affecting brain functional activities, including epilepsy or dementia. * severe cardiac-cerebral vascular disease, including but not limited to: 1. acute myocardial infarction, unstable angina, stroke, or received coronary angioplasty or stent implantation within 6 months before the first dosing. 2. new york heart association functional class ii to iv congestive heart failure or left ventricular ejection fraction (lvef) \< 50% or the lower normal limit. 3. uncontrollable hypertension (even though the best available treatment is used but systolic blood pressure ≥ 160 mmhg or diastolic blood pressure ≥ 100 mmhg). 4. qtcf interval prolongation during the baseline period. * participants with active or history of autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except for clinically stable autoimmune thyroid diseases. * active infection requiring systemic therapy within 7 days prior to the first dosing; active hepatitis b or hepatitis c, history of immunodeficiency virus (hiv) disease or hiv antibody positive. * priorly received allogeneic stem cell transplantation or solid organ transplantation. * known allergy to the zg0895.hcl or any of its excipients; have severe allergy history (ctcae grade ≥ 3), such as severe urticaria, angioedema, severe anaphylaxis, etc. * females who are pregnant or nursing during the screening period. * the investigators consider that the participants are not suitable to participate in the clinical study for other reasons.