A Study of GNC-035 in Relapsed or Refractory Non-Hodgkin 's Lymphoma and Other Hematological Malignancies

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non-hodgkin's Lymphoma
• Intervention / Treatment: Drug: GNC-035

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sa Xiao, PHD; Phone Number: +8615013238943; Email: xiaosa@baili-pharm.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Jun Zhu, PHD; Phone Number: 88196115; Email: zhujun3346@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The subject is able to understand the informed consent form, voluntarily participates, and signs the informed consent form;
2. No gender restrictions;
3. Age: ≥18 years and ≤75 years;
4. Expected survival time ≥3 months;
5. Histologically or cytologically confirmed relapsed or refractory non-Hodgkin's lymphoma;
6. 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;
7. For non-Hodgkin's lymphoma, at least one measurable lesion meeting the Lugano response criteria must be present during the screening period;
8. ECOG performance status score ≤2;
9. Toxicity from prior anti-tumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
10. Organ function levels meet the requirements within 7 days before the first dose;
11. 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 the last dose. Female subjects of childbearing potential must have a negative serum/urine pregnancy test within 7 days before the first dose;
12. 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:

1. 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);
2. Pulmonary diseases classified as ≥Grade 3 according to NCI-CTCAE v5.0;
3. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;
4. Patients with active autoimmune diseases;
5. History of other malignancies within 5 years prior to the first dose;
6. Positive for human immunodeficiency virus (HIV) antibodies, active tuberculosis, active hepatitis B virus (HBV) infection, or hepatitis C virus (HCV) infection;
7. Poorly controlled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg) despite medication;
8. History of severe cardiovascular or cerebrovascular diseases;
9. Patients with a history of hypersensitivity to recombinant humanized antibodies or any excipients of GNC-035;
10. Pregnant or lactating women;
11. Patients with central nervous system involvement;
12. Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
13. Autologous hematopoietic stem cell transplantation (Auto-HSCT) within 12 weeks before initiating GNC-035 treatment;
14. Current use of immunosuppressive therapy;
15. Radiotherapy or macromolecular targeted therapy within 4 weeks before initiating GNC-035 treatment; chemotherapy or small-molecule targeted therapy within 2 weeks or 5 half-lives (whichever is shorter) before treatment;
16. Anti-CD20 or anti-CD79b treatment within 4 weeks before initiating GNC-035 treatment with ongoing response;
17. CAR-T therapy within 12 weeks before initiating GNC-035 treatment;
18. Use of investigational drugs from other clinical trials within 4 weeks or 5 half-lives (whichever is shorter) before the administration of this study;
19. Any other condition deemed unsuitable for participation in this clinical trial by the investigator.

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: 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.	Drug: GNC-035; GNC-035 was administered by intravenous infusion for 2 h-4 h, once a week ( IV, QW ), 3 weeks as a cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase II: Objective Response Rate (ORR)	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.	Up to approximately 24 months
Phase I: Dose limiting toxicity (DLT)	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.	Up to 21 days after the first dose
Phase I: Maximum tolerated dose (MTD)	MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle .	Up to 21 days after the first dose
Phase I: 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-035. The type, frequency and severity of TEAE will be evaluated during the treatment of GNC-035.	Up to approximately 24 months
Phase I: Recommended Phase II Dose (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-035.	Up to 21 days after the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]).	Up to approximately 24 months
Duration of Response (DOR)	The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.	Up to approximately 24 months
Progression-free survival (PFS)	The PFS is defined as the time from the participant's first dose of GNC-035 to the first date of either disease progression or death, whichever occurs first.	Up to approximately 24 months
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-035. The type, frequency and severity of TEAE will be evaluated during the treatment of GNC-035.	Up to approximately 24 months
Phase Ib: T1/2	Half-life (T1/2) of GNC-035 will be investigated.	Up to 21 days after the first dose
Phase I: Objective Response Rate (ORR)	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.	Up to approximately 24 months
Phase I: Complete Response (CR)	Complete response (CR) is defined as all tumor target lesions disappeared, no new lesions appeared, and tumor markers were normal for at least 4 weeks.	Up to approximately 24 months
Phase I: Cmax	Maximum Drug Concentration (Cmax) of GNC-035 will be investigated.	Up to 21 days after the first dose
Phase I: Tmax	Time at Which the Maximum (Tmax) of GNC-035 will be investigated.	Up to 21 days after the first dose
Phase I: AUC0-inf	Area Under the Curve（0-inf）of GNC-035 will be investigated.	Up to 21 days after the first dose
Phase I: AUC0-T	Area Under the Curve（0-t）of GNC-035 will be investigated.	Up to 21 days after the first dose
Phase I: CL	Rate of clearance of GNC-035 will be investigated.	Up to 21 days after the first dose
Phase I: Anti-drug antibody (ADA)	Frequency of anti-GNC-035 antibody (ADA) will be investigated.	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Collaborators: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Jun Zhu, PhD, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: September 27, 2023
• First Submitted That Met QC Criteria: September 27, 2023
• First Posted (Actual): October 4, 2023

Study Record Updates

• Last Update Posted (Estimated): October 1, 2025
• Last Update Submitted That Met QC Criteria: September 26, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Hematological malignancies
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: GNC-035-104

Drug and device information, study documents

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