Gentulizumab in Patients With Advanced Solid Malignancies and Non-Hodgkin Lymphoma
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Experimental cohort Gentulizumab monotherapy 0.1, 0.3, 1, 3, 10, 30, 45 mg/kg administered intravenously once every week. |
Drug: Gentulizumab
Gentulizumab is administered IV once a week, with every 4 weeks as an administration cycle.
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Outcome Measures
Primary Outcome Measures
- 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). [28 days]
The CTCAE criteria will be used to assess adverse events on this trial.
- 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
- Pharmacodynamic (PD) Characteristics of Gentulizumab. [From the first dosing to 90 days after the last dosing]
PD parameters include: receptor occupancy (RO) of gentulizumab of red blood cells, and white blood cells in peripheral blood.
- Immunogenicity of Gentulizumab. [From the first dosing to 28 days after the last dosing]
Numbers of anti-drug antibody (ADA) and/or neutralizing antibody (NAb) positive participants will be used to assess the immunogenicity of gentulizumab.
Other Outcome Measures
- Objective Response Rate (ORR) of Gentulizumab as Monotherapy. [From date of first dosing until the date of disease progression or death due to any cause, whichever came first, assessed up to 12 months.]
ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination.
- Progression-free Survival (PFS) of Gentulizumab as Monotherapy. [From date of first dosing until the date of disease progression or death due to any cause, whichever came first, assessed up to 12 months.]
PFS was defined as the time ranging from the beginning of enrollment to the tumor progression for the first time or death.
- Exploratory indicators related to biomarkers [12 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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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.
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Gender: Male or female.
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Age 18-70 years old.
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Expected survival ≥ 12 weeks.
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Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
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Patients with advanced solid tumors or NHL by histopathological diagnosis do not have acceptable standard treatment currently.
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Adequate organ function per protocol-defined criteria.
Exclusion Criteria:
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Use of protocol-defined prior/concomitant therapy.
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Currently receiving or has received an investigational treatment as part of a study within 4 weeks before the first dosing.
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History of severe hypersensitivity reaction to study treatments or their excipients.
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Known active central nervous system metastases.
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History of any active autoimmune disease history, or disease or syndrome requiring treatment with systemic steroids or immunosuppressive medications.
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Presence of active infection.
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Known additional malignancy that has not been cured in the last 5 years.
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Any uncontrolled intercurrent illness or condition that in the judgment of the Investigator may endanger the patient.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Jian Zhang | Shanghai | Shanghai | China | 20032 |
| 2 | Zhejiang Cancer Hospital | Hangzhou | Zhejiang | China | 310022 |
Sponsors and Collaborators
- GeneScience Pharmaceuticals Co., Ltd.
Investigators
- Principal Investigator: Jian Zhang, Doctor, Fudan University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Gensci059-Ia-A