Study of ZG0895.HCl in Patients With Advanced Solid Tumors

Zelgen Biopharmaceuticals

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: ZG0895 Hydrochloride for Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT05877664

ZG0895-001

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Part1：Dose Escalation

Experimental group

Description:

During the dose-escalation stage, an accelerated titration design (ATD) will be utilized for the first three lower dose groups (0.06, 0.12 and 0.18 mg/m\^2). The conventional "3+3" dose escalation method will be used for the subsequent dose groups. The entire duration of 21 days after the first dose of ZG0895.HCl is defined as the dose-limiting toxicity (DLT) observation period.

Treatment:

Drug: ZG0895 Hydrochloride for Injection