An Open, Multicenter, Phase I / II Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics / Pharmacodynamics and Antitumor Activity of GNC-035 Tetra-specific Antibody Injection in Relapsed or Refractory Non-Hodgkin 's Lymphoma and Other Hematological Malignancies
Overview
- Phase
- Phase 1
- Intervention
- GNC-035
- Conditions
- Non-hodgkin's Lymphoma
- Sponsor
- Sichuan Baili Pharmaceutical Co., Ltd.
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Phase I: Dose limiting toxicity (DLT)
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
Phase I main objectives: To observe the safety and preliminary efficacy of GNC-035 in patients with relapsed/refractory non-Hodgkin lymphoma and other hematological malignancies, to determine the DLT and MTD, or MAD, and to determine RP2D. Phase II Main objective: To explore the efficacy of GNC-035 in patients with relapsed/refractory non-Hodgkin lymphoma and other hematological malignancies.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The subject is able to understand the informed consent form, voluntarily participates, and signs the informed consent form;
- •No gender restrictions;
- •Age: ≥18 years and ≤75 years;
- •Expected survival time ≥3 months;
- •Histologically or cytologically confirmed relapsed or refractory non-Hodgkin's lymphoma;
- •For patients with relapsed or refractory non-Hodgkin's lymphoma, specifically including: Patients who have failed at least one line of standard therapy; Patients with relapsed or refractory disease judged by the investigator to have no other available or suitable treatment options;
- •For non-Hodgkin's lymphoma, at least one measurable lesion meeting the Lugano response criteria must be present during the screening period;
- •ECOG performance status score ≤2;
- •Toxicity from prior anti-tumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
- •Organ function levels meet the requirements within 7 days before the first dose;
Exclusion Criteria
- •Patients who have undergone major surgery within 28 days prior to the administration of this study or are scheduled for major surgery during the study period (major surgery is defined by the investigator);
- •Pulmonary diseases classified as ≥Grade 3 according to NCI-CTCAE v5.0;
- •Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;
- •Patients with active autoimmune diseases;
- •History of other malignancies within 5 years prior to the first dose;
- •Positive for human immunodeficiency virus (HIV) antibodies, active tuberculosis, active hepatitis B virus (HBV) infection, or hepatitis C virus (HCV) infection;
- •Poorly controlled hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg) despite medication;
- •History of severe cardiovascular or cerebrovascular diseases;
- •Patients with a history of hypersensitivity to recombinant humanized antibodies or any excipients of GNC-035;
- •Pregnant or lactating women;
Arms & Interventions
Study treatment
Participants receive GNC-035 as intravenous infusion for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
Intervention: GNC-035
Outcomes
Primary Outcomes
Phase I: Dose limiting toxicity (DLT)
Time Frame: Up to 21 days after the first dose
DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration.
Phase I: Recommended Phase II Dose (RP2D)
Time Frame: Up to 21 days after the first dose
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of GNC-035.
Phase I: Maximum tolerated dose (MTD)
Time Frame: Up to 21 days after the first dose
MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle .
Phase II: Objective Response Rate (ORR)
Time Frame: Up to approximately 24 months
ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.
Phase I: Treatment-Emergent Adverse Event (TEAE)
Time Frame: Up to approximately 24 months
TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of GNC-035. The type, frequency and severity of TEAE will be evaluated during the treatment of GNC-035.
Secondary Outcomes
- Disease Control Rate (DCR)(Up to approximately 24 months)
- Phase I: Objective Response Rate (ORR)(Up to approximately 24 months)
- Duration of Response (DOR)(Up to approximately 24 months)
- Phase I: Complete Response (CR)(Up to approximately 24 months)
- Progression-free survival (PFS)(Up to approximately 24 months)
- Phase I: AUC0-T(Up to 21 days after the first dose)
- Phase I: Tmax(Up to 21 days after the first dose)
- Phase I: AUC0-inf(Up to 21 days after the first dose)
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Phase I: CL(Up to 21 days after the first dose)
- Phase I: Anti-drug antibody (ADA)(Up to approximately 24 months)
- Phase I: Cmax(Up to 21 days after the first dose)
- Phase Ib: T1/2(Up to 21 days after the first dose)