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

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)

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

Study Overview

• Status: Recruiting
• Conditions: Non-hodgkin's Lymphoma
• Intervention / Treatment: Drug: GNC-038

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

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

Contacts and Locations

• Study Contact: Name: Sa Xiao, PHD; Phone Number: +86-15013238943; Email: xiaosa@baili-pharm.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Jun Zhu; Phone Number: 010-88196115; Email: zhujun3346@163.com
      • Principal Investigator: Yuqin Song
      • Contact: Yuqin Song; Phone Number: 010-88196118; Email: SongYQ_VIP@163.com
      • Principal Investigator: Jun Zhu
  • Heilongjing
    • Haerbin, Heilongjing, China
      • Recruiting
      • Harbin First Hospital
      • Contact: Zhiguo Wang
  • Shandong
    • Qingdao, Shandong, China
      • Recruiting
      • Qingdao Central Hospital
      • Contact: Ling Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The subject is capable of understanding 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. Patients with histologically confirmed non-Hodgkin's lymphoma;
6. Patients with relapsed or refractory non-Hodgkin's lymphoma (R/R NHL);
7. 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);
8. ECOG performance status score ≤2;
9. Adverse reactions from prior anti-tumor treatment have recovered to ≤Grade 1 as per CTCAE 5.0 criteria;
10. Organ function levels meet the requirements 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 treatment discontinuation. 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. Pulmonary diseases classified as ≥Grade 3 according to NCI-CTCAE v5.0; patients currently diagnosed with interstitial lung disease (ILD);
2. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;
3. Active tuberculosis;
4. Patients with active autoimmune diseases;
5. History of other malignancies within 5 years prior to the first dose;
6. 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;
7. Poorly controlled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg);
8. History of severe cardiovascular or cerebrovascular diseases;
9. Patients with a history of hypersensitivity to recombinant humanized antibodies or any excipients of GNC-038;
10. Pregnant or lactating women;
11. Patients with central nervous system involvement;
12. Major surgery within 28 days before the first dose of this study or planned major surgery during the study period;
13. Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
14. Autologous hematopoietic stem cell transplantation (Auto-HSCT) within 12 weeks before initiating GNC-038 treatment;
15. Current use of immunosuppressive therapy;
16. Radiotherapy within 4 weeks before initiating GNC-038 treatment;
17. Chemotherapy or small-molecule targeted therapy within 2 weeks or 5 half-lives prior to treatment;
18. CAR-T therapy within 12 weeks before initiating GNC-038 treatment;
19. Use of any other investigational drug in a clinical trial within 4 weeks or 5 half-lives before the first dose of this study;
20. 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: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study treatment; Participants receive GNC-038 as intravenous infusion for the first cycle (2 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; Administration by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity (DLT)	The incidence and severity of adverse events (TEAE) during treatment were graded according to the National Cancer Institute Standard for Common Terminology for Adverse Events (NCI-CTCAE, v5.0).	Up to 14 days after the first dose
Maximum tolerated dose (MTD) or Maximum 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 14 days after the first dose
Adverse Events during Treatment (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
Recommended dose for Phase II clinical studies (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 14 days after the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease control rate (DCR)	Number of patients showing Complete Response (CR) or Partial Response (PR) based on RECIST for the best response. Number of patients showing Complete Response (CR, disappearance of all target lesions) or Partial Response (PR, at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) based on RECIST Criteria Version 1.0 (assessed by CT and/or MRI) for the best response.	Up to approximately 24 months
progression-free survival (PFS)	The PFS is defined as the time from the participant's first dose of GNC-038 to the first date of either disease progression or death, whichever occurs first.	Up to approximately 24 months
Adverse Events of Special Interest (AESI)	AESI is an event of scientific and medical interest specific to the sponsor's product or research project.	Up to approximately 24 months
Cmax	Maximum serum concentration (Cmax) of GNC-038 will be investigated.	Up to approximately 24 months
Tmax	Time to maximum serum concentration (Tmax) of GNC-038 will be investigated.	Up to approximately 24 months
AUC0-INF	Blood concentration - Area under time line.	Up to approximately 24 months
AUC0-T	Blood concentration - Area under time line.	Up to approximately 24 months
T1/2	Blood concentration - Area under time line.	Up to approximately 24 months
anti-drug antibody (ADA) in Ⅰa	Frequency and titer of anti-GNC-038 antibody (ADA).	Up to approximately 24 months
DOR (Duration of Response)	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutralizing antibody (Nab) in phase Ⅰb	Incidence and titer of Nab of GNC-038 will be evaluated.	Up to approximately 24 months
Overall survival (OS) in phaseⅠb and phase Ⅱ	The time between the start of study medication and death.	Up to approximately 24 months
Neutralizing antibody (Nab) in phaseⅡ	Incidence and titer of Nab of GNC-038 will be evaluated.	Up to approximately 24 months
anti-drug antibody (ADA) in phaseⅡ	Frequency and titer of anti-GNC-038 antibody (ADA) will be evaluated.	Up to approximately 24 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: August 25, 2022
• First Submitted That Met QC Criteria: November 13, 2022
• First Posted (Actual): November 21, 2022

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 26, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: GNC-038-104

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