A Study of GNC-038 Injection in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Official title

An Open, Multicenter, Phase Ib/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Tetra-specific Antibody GNC-038 Injection in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma (NHL)

Overview

To explore the safety and preliminary efficacy of GNC-038 in patients with relapsed or refractory NHL, and to determine the MTD and RP2D of GNC-038, or the MAD and DLT

Detailed description

phase Ib: To explore the safety and preliminary efficacy of GNC-038 in patients with relapsed or refractory NHL, and to determine the MTD and RP2Dof GNC-038, or the MAD and DLT of GNC-038 if MTD is not reached, by intravenous infusion (IV, QW) once a week (2 weeks as a cycle) phase II To explore the efficacy of GNC-038 in patients with relapsed or refractory non-Hodgkin's lymphoma

Interventions

• Drug GNC-038
  Administration by intravenous infusion

Primary outcome measures

• Dose limiting toxicity (DLT) [Time frame: Up to 14 days after the first dose]
• Maximum tolerated dose (MTD) or Maximum dose (MAD) [Time frame: Up to 14 days after the first dose]
• Adverse Events during Treatment (TEAE) [Time frame: Up to approximately 24 months]
• Recommended dose for Phase II clinical studies (RP2D) [Time frame: Up to 14 days after the first dose]

Secondary outcome measures (10)

• disease control rate (DCR) [Time frame: Up to approximately 24 months]
• progression-free survival (PFS) [Time frame: Up to approximately 24 months]
• Adverse Events of Special Interest (AESI) [Time frame: Up to approximately 24 months]
• Cmax [Time frame: Up to approximately 24 months]
• Tmax [Time frame: Up to approximately 24 months]
• AUC0-INF [Time frame: Up to approximately 24 months]
• AUC0-T [Time frame: Up to approximately 24 months]
• T1/2 [Time frame: Up to approximately 24 months]
• anti-drug antibody (ADA) in Ⅰa [Time frame: Up to approximately 24 months]
• DOR (Duration of Response) [Time frame: Up to approximately 24 months]

Eligibility criteria

Inclusion criteria

• The subject is capable of understanding 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;
• Patients with histologically confirmed non-Hodgkin's lymphoma;
• Patients with relapsed or refractory non-Hodgkin's lymphoma (R/R NHL);
• Presence of measurable lesions during the screening period (lymph node lesions with any long diameter ≥1.5 cm or extranodal lesions with any long diameter >1.0 cm);
• ECOG performance status score ≤2;
• Adverse reactions from prior anti-tumor treatment have recovered to ≤Grade 1 as per CTCAE 5.0 criteria;
• Organ function levels meet the requirements before the first dose;
• Female subjects of childbearing potential or male subjects with partners of childbearing potential must use highly effective contraception from 7 days before the first dose until 12 weeks after treatment discontinuation. Female subjects of childbearing potential must have a negative serum/urine pregnancy test within 7 days before the first dose;
• The subject has the ability and willingness to comply with the study protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.

Exclusion criteria

• Pulmonary diseases classified as ≥Grade 3 according to NCI-CTCAE v5.0; patients currently diagnosed with interstitial lung disease (ILD);
• Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;
• Active tuberculosis;
• Patients with active autoimmune diseases;
• History of other malignancies within 5 years prior to the first dose;
• HBsAg-positive and/or HBcAb-positive with HBV-DNA levels ≥ the lower limit of detection; HCV antibody-positive with HCV-RNA levels ≥ the lower limit of detection; HIV antibody-positive;
• Poorly controlled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg);
• History of severe cardiovascular or cerebrovascular diseases;
• Patients with a history of hypersensitivity to recombinant humanized antibodies or any excipients of GNC-038;
• Pregnant or lactating women;
• Patients with central nervous system involvement;
• Major surgery within 28 days before the first dose of this study or planned major surgery during the study period;
• Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
• Autologous hematopoietic stem cell transplantation (Auto-HSCT) within 12 weeks before initiating GNC-038 treatment;
• Current use of immunosuppressive therapy;
• Radiotherapy within 4 weeks before initiating GNC-038 treatment;
• Chemotherapy or small-molecule targeted therapy within 2 weeks or 5 half-lives prior to treatment;
• CAR-T therapy within 12 weeks before initiating GNC-038 treatment;
• Use of any other investigational drug in a clinical trial within 4 weeks or 5 half-lives before the first dose of this study;
• Any other condition deemed unsuitable for participation in this clinical trial by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 3 centers

• Beijing Cancer Hospital — Beijing
• Harbin First Hospital — Haerbin
• Qingdao Central Hospital — Qingdao

Identifiers

NCT: NCT05623982 · GNC-038-104

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗