A Study of GNC-035 in Relapsed or Refractory Chronic Lymphocytic Leukemia and Other Hematological Malignancies

NCT05944978 | Active Not Recruiting Phase 1

• 1 other identifier: GNC-035-105
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

An open-label, multicenter, phase Ib/II clinical trial was conducted to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of GNC-035 quad-specific antibody injection in patients with relapsed or refractory chronic lymphocytic leukemia and other hematological malignancies

Conditions

Relapsed/Refractory Chronic Lymphocytic Leukemia

Keywords

Hematological malignancies

Outcome Measures

Primary Outcomes (5)

• Phase Ib: 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 Ib: 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 Ib: 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: 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

• 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

Secondary Outcomes (13)

• Phase Ib: Objective Response Rate (ORR)

  Up to approximately 24 months

• Progression-free survival (PFS)

  Up to approximately 24 months

• Disease Control Rate (DCR)

  Up to approximately 24 months

• Duration of Response (DOR)

  Up to approximately 24 months

• Phase Ib: Complete Response (CR)

  Up to approximately 24 months

Study Arms (1)

Study treatment

EXPERIMENTAL

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

Interventions

GNC-035 DRUG

GNC-035 was intravenously infused 2h to 4h, once a week (IV, QW), and a 3-week cycle was used.

Study treatment

Eligibility Criteria

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

You may qualify if:

• Subjects can understand the informed consent form, voluntarily participate in and sign the informed consent form;
• No gender limit;
• Age: ≥18 years old (≤75 years old for climbing);
• expected survival time ≥3 months;
• Patients with hematological malignancies such as relapsed/refractory chronic lymphocytic leukemia confirmed by histology or cytology;
• For relapsed or refractory chronic lymphocytic leukemia (CLL/SLL), specifically:
• Patients who have relapsed after at least one line of standard therapy or have no response to or intolerance to standard regimens; Patients with relapsed or refractory chronic lymphocytic leukemia who were not or were ineligible for/intolerant of other therapies according to investigator assessment.
• Relapsed and refractory were defined as follows:
• Relapse was defined as disease progression after a response to adequate treatment, including at least one regimen containing a BTK inhibitor.
• Refractory was defined as refractory to BTK inhibitor, failure to achieve remission after adequate treatment with BTK inhibitor-containing regimens (combination therapy or monotherapy), or disease progression during treatment or within 6 months after completion of adequate treatment.
• For other patients with relapsed refractory non-Hodgkin lymphoma. These include:
• Patients who experience failure of at least two lines of therapy; Relapsed or refractory patients who are not or are ineligible for/intolerant of other therapies as judged by the investigator.
• Relapsed and refractory were defined as follows:
• Relapse was defined as disease progression after a response to adequate treatment, including at least one anti-CD20 monoclonal antibody.
• Refractory was defined as refractory to anti-CD20 monoclonal antibody, failure to achieve remission after adequate treatment with anti-CD20 monoclonal antibody (combination therapy or monotherapy), or disease progression during treatment or 6 months after completion of adequate treatment.

You may not qualify if:

• Patients who underwent major surgery within 28 days before study administration or who were scheduled to undergo major surgery during the study (" major surgery "was defined by the investigator);
• Pulmonary disease grade ≥3 according to NCI-CTCAE v5.0, including dyspnea at rest or requiring continuous oxygen therapy; Patients with current interstitial lung disease (ILD) (except those who have recovered from previous interstitial pneumonia);
• Severe systemic infection occurred within 4 weeks before screening, including but not limited to severe pneumonia caused by fungi, bacteria, or viruses, bacteremia, or serious infectious complications;
• Patients with active autoimmune disease or a history of autoimmune disease. Patients with type I diabetes mellitus, hypothyroidism that is stable with hormone-replacement therapy (including hypothyroidism due to autoimmune thyroid disease), psoriasis, or vitiligo that does not require systemic therapy, as deemed by the investigators, were excluded.
• Patients with other malignant tumors within 3 years before the first drug administration, cured non-melanoma skin cancer in situ, superficial bladder cancer, cervical cancer in situ, gastrointestinal mucosal cancer, breast cancer, localized prostate cancer, and other patients without recurrence within 3 years were excluded.
• Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBsAg positive or HBcAb positive and HBV-DNA test ≥ central detection lower limit) or hepatitis C virus infection (HCV antibody positive and HCV-RNA≥ central detection lower limit);
• Hypertension poorly controlled by medication (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg);
• Left ventricular ejection fraction ≤45%, or history of major heart disease within 1 year:
• New York Heart Association (NYHA) class III or IV congestive heart failure;
• Acute coronary syndrome, myocardial infarction or bypass or stent surgery (except those judged by the investigator to be stable);
• Patients with unstable angina pectoris;
• QT prolongation (QTcf \> 450 msec in men or \> 470 msec in women), complete left bundle branch block, degree III atrioventricular block, and arrhythmia requiring medical intervention;
• Other cardiac conditions deemed by the investigator to be ineligible for enrollment.
• Patients with a history of allergy to recombinant humanized antibodies or to any of the excipients of GNC-035;
• Women who are pregnant or breastfeeding;

Sponsors & Collaborators

• Sichuan Baili Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site

Study Officials

• Lugui Qiu, MS

  Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

• Shuhua Yi, PHD

  Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 6, 2023
• First Posted: July 14, 2023
• Study Start: August 16, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: September 26, 2025

Record last verified: 2025-09

Locations

CN (1)