A Phase 1 Dose Escalation and Expansion, Tolerability, Safety, Pharmacokinetics / Pharmacodynamics and Preliminary Efficacy Study of ZG0895.HCl in Patients With Advanced Solid Tumors

ZG0895-001

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.

2023-08-08

2026-06-01

2026-06-01

Recruiting

Early phase I

60

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 60, 'type': 'ESTIMATED'}}

2024-03-06