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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor; Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: Gentulizumab

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 Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 20032
      • Jian Zhang
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) of Gentulizumab as Monotherapy.	ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination.	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.
Progression-free Survival (PFS) of Gentulizumab as Monotherapy.	PFS was defined as the time ranging from the beginning of enrollment to the tumor progression for the first time or death.	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.
Exploratory indicators related to biomarkers		12 months

Collaborators and Investigators

• Sponsor: Changchun GeneScience Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Jian Zhang, Doctor, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2021
• Primary Completion (Actual): May 30, 2023
• Study Completion (Actual): October 27, 2023

Study Registration Dates

• First Submitted: December 27, 2021
• First Submitted That Met QC Criteria: January 21, 2022
• First Posted (Actual): February 3, 2022

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: Gensci059-Ia-A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No