Gentulizumab in Patients With Advanced Solid Malignancies and Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of gentulizumab, an anti-CD47 Monoclonal Antibody, in participants with solid tumors and non-Hodgkin lymphoma.

Detailed Description
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This is a first-in-human, escalating dose trial of an antibody that inhibits an anti-apoptotic signal in human macrophages. The major aims of the study are to define the safety profile of this new drug, and to determine a recommended dose and schedule for potential additional trials.

Official Title
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A Phase Ia, Open-label, Dose Escalation Study of Safety, Tolerability, Pharmacokinetics of Gentulizumab, an Anti-CD47 Monoclonal Antibody, in Patients With Advanced Solid Malignancies and Non-Hodgkin Lymphoma (NHL)

Conditions
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Solid Tumor, Non-Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Gentulizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has the willingness to communicate with the investigator, can understand and follow the trial requirements, is willing to participate in the trial, understands and signs a written Informed Consent Form（ICF）, and is willing and able to comply with the visit schedule, administration plan, laboratory examination, and other clinical trial procedures. Gender: Male or female. Age 18-70 years old. Expected survival ≥ 12 weeks. Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Patients with advanced solid tumors or NHL by histopathological diagnosis do not have acceptable standard treatment currently. Adequate organ function per protocol-defined criteria. Exclusion Criteria: Use of protocol-defined prior/concomitant therapy. Currently receiving or has received an investigational treatment as part of a study within 4 weeks before the first dosing. History of severe hypersensitivity reaction to study treatments or their excipients. Known active central nervous system metastases. History of any active autoimmune disease history, or disease or syndrome requiring treatment with systemic steroids or immunosuppressive medications. Presence of active infection. Known additional malignancy that has not been cured in the last 5 years. Any uncontrolled intercurrent illness or condition that in the judgment of the Investigator may endanger the patient.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental cohort<br>Gentulizumab monotherapy 0.1, 0.3, 1, 3, 10, 30, 45 mg/kg administered intravenously once every week. | Drug: Gentulizumab<br>* Gentulizumab is administered IV once a week, with every 4 weeks as an administration cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of Gentulizumab as Measured by the Number of Participants Experiencing Dose-limiting Toxicities (DLTs), Adverse Events (AEs), and Serious Adverse Events (SAEs). | The CTCAE criteria will be used to assess adverse events on this trial. | 28 days | 
| Pharmacokinetic (PK) Parameter: Area under the plasma concentration versus time curve (AUC). |  | From the first dosing to 90 days after the last dosing | 
| Pharmacokinetic (PK) Parameter: Peak plasma concentration (Cmax). |  | From the first dosing to 90 days after the last dosing | 
| Pharmacokinetic (PK) Parameter: Terminal phase half-life (t1/2). |  | From the first dosing to 90 days after the last dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamic (PD) Characteristics of Gentulizumab. | PD parameters include: receptor occupancy (RO) of gentulizumab of red blood cells, and white blood cells in peripheral blood. | From the first dosing to 90 days after the last dosing | 
| Immunogenicity of Gentulizumab. | Numbers of anti-drug antibody (ADA) and/or neutralizing antibody (NAb) positive participants will be used to assess the immunogenicity of gentulizumab. | From the first dosing to 28 days after the last dosing |