A Study of GNC-038, a Tetra-specific Antibody, in Participants With R/R Diffuse Large B-cell Lymphoma (DLBCL)

NCT05192486 | Active Not Recruiting Phase 1

• 1 other identifier: GNC-038-102
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 4

Brief Summary

In this study, the safety and preliminary efficacy of GNC-038 in participants with recurrent or refractory Diffuse Large B-cell lymphoma (DLBCL) will be investigated to assess the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) or maximum administered dose (MAD) for MTD is not reached of GNC-038. The recommended dose for phase II (RP2D) clinical study will also be determined.

Conditions

Diffuse Large B-cell Lymphoma

Keywords

DLBCL

Outcome Measures

Primary Outcomes (4)

• Dose limiting toxicity (DLT)

  The incidence and severity of adverse events during treatment were graded according to the National Cancer Institute Standard for Common Terminology for Adverse Events (NCI-CTCAE, v5.0).

  Up to 21 days after the first dose of GNC-038

• Maximum tolerated dose (MTD) or maximum administrated dose (MAD)

  In the dose increment stage, the highest dose whose estimated DLT rate is closest to the target DLT rate but does not exceed the upper bound of the equivalent interval of DLT rate is selected as MTD.

  Up to 21 days after the first dose of GNC-038

• Treatment-Emergent Adverse Event (TEAE)

  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-038. The type, frequency and severity of TEAE will be evaluated during the treatment of GNC-038.

  Up to approximately 24 months

• The recommended dose for phase II clinical study（RP2D）

  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-038.

  Up to 21 days after the first dose of GNC-038

Secondary Outcomes (15)

• ORR (Objective Response Rate )

  Up to approximately 24 months

• PFS (Progression-free Survival)

  Up to approximately 24 months

• DCR (Disease Control Rate)

  Up to approximately 24 months

• DOR (Duration of Response)

  Up to approximately 24 months

• CR (Complete Response)

  Up to approximately 24 months

Study Arms (1)

Study treatment

EXPERIMENTAL

Participants receive GNC-038 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.

Drug: GNC-038

Interventions

GNC-038 DRUG

Administration by intravenous infusion

Study treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• he participants could understand and sign the informed consent form, and must participate voluntarily;
• No gender limit;
• Age: ≥18 years old and ≤75 years;
• Expected survival time ≥ 3 months;
• Has suffered from Diffuse Large B-cell lymphoma (DLBCL) confirmed by histology or cytology;
• a. Those who have recurrent or refractory Diffuse Large B-cell lymphoma (DLBCL).
• b. Recurrent or refractory participants that are, determined by the investigators, not applicable/tolerated to other treatments.
• Recurrent and refractory are defined as follows:
• Recurrent is the progression of disease after adequate treatment to remission, with at least one regimen containing rituximab.
• Refractory refers to failure to respond to adequate treatment with rituximab containing regimen (combination chemotherapy or monotherapy) or disease progression during treatment/within 6 months of completion of adequate treatment.
• "Adequate treatment with rituximab regimen" refers to the completion of rituximab combined with chemotherapy based on pathological type and disease stage requirements, or rituximab monotherapy with 375 mg/m2 injections at least 4 times a week. "Progress during treatment" requires completion of at least one cycle of rituximab plus chemotherapy or monotherapy if progress during induction therapy; At least one injection is completed if progress is made during maintenance therapy. "Mitigation" includes complete and partial mitigation.
• There are measurable lesions during the screening period (any long diameter of lymph node lesions ≥ 1.5 cm or any long diameter of extra-nodal lesions greater than 1.0 cm);
• Physical fitness score ECOG≤2；
• The toxicity of the previous anti-tumor therapy has been restored to the level ≤1 defined by NCI-CTCAE v5.0 (the investigators considered indicators that might be associated with the disease, such as anemia, and excluded toxicities that the investigators considered to be of no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism stabilized by hormone replacement therapy);
• The organ function within 7 days prior to the first administration meets the following requirements:

You may not qualify if:

• Has grade 3 or above lung disease defined according to NCI-CTCAE v5.0; Patients with current interstitial lung disease (ILD) (except those who have recovered from previous interstitial pneumonia;
• Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc;
• Active tuberculosis;
• Participants at risk of active autoimmune diseases, such as: systemic lupus erythematosus, systemic treatment of psoriasis, rheumatoid arthritis, inflammatory bowel disease, and hashimoto's thyroiditis, etc., with the exception of type I diabetes, only replacement therapy can control the hypothyroidism, no systemic treatment of skin disease (such as vitiligo, psoriasis), B cells caused by autoimmune disease;
• Complicated with other malignant tumors within 5 years prior to GNC-038 treatment, except for non-melanoma skin cancer in situ, superficial bladder cancer, cervical cancer in situ, gastrointestinal intramucosal cancer, breast cancer and localized prostate cancer that have been cured and have not recurred within 5 years;
• HBsAg or HBcAb positive and HBV-DNA test ≥ULN; HCV antibody positive and HCV-RNA≥ULN; HIV antibody positive;
• Participants with poorly controlled hypertension by antihypertensive drugs (systolic blood pressure\>150 mmHg or diastolic blood pressure\>100 mmHg);
• History of severe heart disease, including but not limited to:
• There are serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias, III grade atrioventricular block, which require clinical intervention;
• Participants with prolonged QT interval (male QTc \> 450 msec or female QTc \> 470 msec);
• Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or above cardiovascular and cerebrovascular events occurred within 6 months before the first administration;
• New York Heart Association (NYHA) grade II, III or IV congestive heart failure;
• Patients with a history of allergy to recombinant humanized antibodies or to any excipient component of GNC-038;
• Pregnant or breastfeeding women;
• There is an invasion of the central nervous system;

Sponsors & Collaborators

• Sichuan Baili Pharmaceutical Co., Ltd.: lead
• SystImmune Inc.: collaborator

Study Sites (4)

Shenzhen Second People's Hospital

Shenzhen, Guangdong, China

Location

Affiliated Hospital of Hebei University

Baoding, Hebei, China

Location

The First Affiliated Hospital of Henan University of Science and Technology

Luoyang, Henan, China

Location

Ruijin Hospital, Shanghai JiaoTong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Weili Zhao

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2021
• First Posted: January 14, 2022
• Study Start: August 10, 2022
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)