A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of HLX51 (Anti-OX40 Monoclonal Antibody) in Patients With Advanced/Metastatic Solid Tumor or Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- HLX51
- Conditions
- Solid Tumor, Adult Lymphoma
- Sponsor
- Shanghai Henlius Biotech
- Enrollment
- 30
- Primary Endpoint
- The Dose-Limiting Toxicity (DLT) of HLX51 within 3 weeks after the first Administration
- Status
- Not Yet Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This study is a first-in-class open-label phase I human clinical study to evaluate the safety and tolerability of HLX51 with escalated doses in the treatment of patients with advanced/metastatic solid tumors or lymphomas.
Detailed Description
This study is the first-in-class open-label phase I human clinical study to evaluate the safety and tolerability of HLX51 with escalated doses in the treatment of patients with advanced/metastatic solid tumors or lymphomas. In this study, 3 + 3 dose escalation method will be adopted, and the patients will be given different doses of HLX51 intravenously. Observation period of DLT lasts for 3 weeks after the first administration of HLX51.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Have a full understanding of the study content, process, and possible adverse reactions before the study, and sign the informed consent form (ICF). voluntarily participate in the study. be able to complete the study as per protocol requirements.
- •Aged ≥ 18 years at the time of signing the ICF.
- •Patients with histologically or cytologically confirmed advanced malignant solid tumor or lymphoma, who have failed or cannot receive the standard treatment.
- •With at least one measurable lesion according to RECIST V1.1 (for solid tumors) or the Lugano criteria (for lymphomas).
- •Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1 at enrollment.
- •Expected survival \> 3 months.
- •Have appropriate hematological functions: no blood transfusion or colony stimulating factor therapy (G-CSF) within 14 days before the first administration. absolute neutrophil count ≥ 1500/μL. haemoglobin ≥ 9 g/dL. platelet count ≥ 90,000/μL.
- •Have appropriate coagulation functions: activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. prothrombin time (PT) ≤ 1.5 × ULN. international normalized ratio (INR) ≤ 1.5 × ULN.
- •Have appropriate liver functions: total bilirubin level ≤ 1.5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN (AST and ALT ≤ 5 × ULN for patients with known liver metastasis or primary hepatocellular carcinoma).
- •Have appropriate renal functions: blood creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min (calculated by Cockcroft-Gault formula).
Exclusion Criteria
- •Previous exposure to any anti-OX40 antibody or any drug targeting T-cell costimulatory signaling pathway.
- •The adverse reactions (except alopecia and other adverse reactions determined by the investigator to have no safety risk) of previous anti-tumor therapy have not yet recovered to ≤ grade 1 (CTCAE V5.0).
- •Those who are known to have severe anaphylaxis to macromolecular protein preparations/monoclonal antibodies or to any component of the investigational product.
- •Patients with any of the following unstable or poorly controlled diseases:
- •Active systemic infectious diseases requiring intravenous antibiotics within 2 weeks before the first administration of the investigational product.
- •Any poorly-controlled cardiovascular and cerebrovascular clinical symptoms or diseases, including but not limited to: (1) NYHA Class II or greater cardiac failure or left ventricular ejection fraction (LVEF) \< 50%. (2) unstable angina pectoris. (3) myocardial infarction and cerebral infarction within 6 months, (4) clinically significant supraventricular or ventricular arrhythmia without clinical intervention or poorly controlled after clinical intervention.
- •Other chronic diseases which, in the opinion of the investigator, may compromise the safety of the patient or the integrity of the study.
- •Assessed as unsuitable for inclusion by the investigator, due to brain metastases, spinal cord compression, or cancerous meningitis with clinical symptoms, or uncontrolled brain or spinal cord metastases that have been evidenced.
- •Previous grade 3 or greater irAEs in immunotherapy.
- •Have had other malignant tumors within 5 years before enrollment, except: (a) those with cured cervical carcinoma in situ or non-melanoma skin cancer. (b) those with cured second primary cancer without recurrence within 5 years. (c) those with double primary cancers believed to be able to benefit from this study. (d) those whose metastasis has been clearly excluded from a certain primary tumor source.
Arms & Interventions
HLX51 Group
The initial dose of HLX51 is 0.3mg/kg, and 5 dose levels are designed: 0.3 mg/kg, 1 mg/kg , 2.5mg/kg, 5mg/kg, and 10mg/kg (Q3W). Patients with good tolerability and well controlled disease will receive the treatment until progressive disease (PD) without any clinical benefit, initiation of other anti-tumor therapies, death, intolerable toxicity, or withdraw the informed consent (whichever occurs first).
Intervention: HLX51
Outcomes
Primary Outcomes
The Dose-Limiting Toxicity (DLT) of HLX51 within 3 weeks after the first Administration
Time Frame: At the end of Cycle 1 (each cycle is 21 days)
DLT refers to the AEs that are determined to be related to the investigational product by the investigator, whose severity will affect the escalation of dose level. In this study, the DLT observation period lasts for 3 weeks after the first administration of HLX51
The maximum tolerated dose (MTD) of HLX51 within 3 weeks after the first administration
Time Frame: At the end of Cycle 1 (each cycle is 21 days)
MTD refers to the highest dose at which less than 1/3 of subjects in the same dose group develop DLT in cycle 1 of the dose escalation stage.