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Relapsed/Refractory Chronic Lymphocytic LeukemiaPhase 1/2NCT05944978

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

A Phase 1/2 study testing GNC-035 in people with Relapsed/Refractory Chronic Lymphocytic Leukemia, run by Sichuan Baili Pharmaceutical Co., Ltd. at 1 site in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
GNC-035
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteChina
Study dates
16 Aug 2023to Dec 2025
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.
  • Among them, "adequate treatment with anti-CD20 monoclonal antibody" refers to the completion of full cycle of anti-CD20 monoclonal antibody combined with chemotherapy according to pathological type and disease stage, or anti-CD20 monoclonal antibody monotherapy at a dose of 375 mg/m2 once a week for at least 4 injections. Progression during treatment required the completion of at least one cycle of anti-CD20 monoclonal antibody combined with chemotherapy or monotherapy if progression occurred during induction therapy. At least one dose was completed if progression occurred during maintenance therapy. "Response" included complete and partial responses.
  • CLL/SLL: peripheral blood leukemia cells ≥5.0×109/L; Or the long diameter of any lymph node lesion ≥1.5cm; Patients with non-Hodgkin's lymphoma had measurable disease at screening (nodal disease ≥1.5cm in the greatest dimension or extranodal disease > 1.0cm in the greatest dimension).
  • ECOG ≤2;
  • Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by NCI-CTCAE v5.0 (except alopecia);
  • Organ function within 7 days before the first dose:
  • Bone marrow function (for patients with non-Hodgkin lymphoma only) : without blood transfusion, G-CSF (for 2 weeks), and medication correction within 7 days prior to screening; Absolute neutrophil count (ANC) ≥1.0×109/L (≥0.5×109/L if the subject has bone marrow infiltration); Hemoglobin ≥80 g/L (≥70g/L if the subject has bone marrow infiltration); Platelet count ≥75×109/L; Liver function: total bilirubin, ≤1.5 ULN (Gilbert's syndrome, ≤3 ULN), and aminotransferase (AST/ALT), ≤2.5 ULN (for those with liver tumor invasive changes, ≤5.0 ULN) without correction with hepatoprotective medication within 7 days before screening examination; Renal function: creatinine (Cr) ≤1.5 ULN or creatinine clearance (Ccr) ≥60 mL/ minute (based on center calculation criteria) Coagulation: activated partial thromboplastin time (APTT) ≤1.5×ULN Prothrombin time (PT) ≤1.5×ULN.
  • Female subjects of childbearing potential or male subjects with a fertile partner 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;
  • Participants were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.

Who cannot join

  • 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);
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  • 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;
  • Presence of central nervous system invasion;
  • Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (ALLo-HSCT);
  • Autologous hematopoietic stem cell transplantation (Auto-HSCT) within 12 weeks before starting GNC-035 therapy;
  • Current use of immunosuppressive agents, including, but not limited to, cyclosporine, tacrolimus, etc., within 2 weeks or 5 half-life periods prior to GNC-035 treatment, whichever is shorter;
  • Received radiotherapy, macromolecular targeted drugs within 4 weeks before GNC-035 treatment; Chemotherapy and a small-molecule targeted agent were administered 2 weeks or within five half-lives before treatment, whichever was less.
  • Received anti-CD20 therapy within 4 weeks prior to GNC-035 therapy and is responding;
  • Received CAR-T therapy within 12 weeks before GNC-035 treatment;
  • Use of a study drug from another clinical trial within 4 weeks or 5 half-lives, whichever was shorter, before the trial dose;
  • Other circumstances that the investigator deemed inappropriate for participation in the trial.

Trial locations and contacts

1 site in 1 country.

China1 site

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

    Tianjin, Tianjin Municipality, 300020

Other trials in China

About this study

Official title: Phase Ib/II Clinical Study of GNC-035 Tetra-specific Antibody Injection in Relapsed or Refractory Chronic Lymphocytic Leukemia and Other Hematological Malignancies

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

Read the detailed description

Phase Ib: To observe the safety and tolerability of GNC-035 in patients with hematologic malignancies such as relapsed/refractory chronic lymphocytic leukemia, and to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), or maximum dose if MTD is not reached (MAD), of GNC-035. To determine the recommended phase II dose (RP2D) in hematologic malignancies such as chronic lymphocytic leukemia. Phase II: To explore the efficacy of GNC-035 in patients with relapsed/refractory chronic lymphocytic leukemia and other hematological malignancies.

Being tested
GNC-035
Keywords
Hematological malignancies
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GNC-035Drug

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

Study groups in NCT05944978
Study groupRoleWhat they receive
Study treatmentExperimentalParticipants 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.
Receives: Drug: GNC-035

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 21 days after the first dose

  2. 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 .

    Measured: Up to 21 days after the first dose

  3. 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.

    Measured: Up to approximately 24 months

  4. 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.

    Measured: Up to 21 days after the first dose

  5. 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.

    Measured: Up to approximately 24 months

Secondary outcomes (13)

  1. Phase Ib: 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.

    Measured: Up to approximately 24 months

  2. 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.

    Measured: Up to approximately 24 months

  3. 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]).

    Measured: Up to approximately 24 months

  4. 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.

    Measured: Up to approximately 24 months

  5. Phase Ib: 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.

    Measured: Up to approximately 24 months

  6. 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.

    Measured: Up to approximately 24 months

  7. Phase Ib: Cmax

    Maximum Drug Concentration (Cmax) of GNC-035 will be investigated.

    Measured: Up to 21 days after the first dose

  8. Phase Ib: Tmax

    Time at Which the Maximum (Tmax) of GNC-035 will be investigated.

    Measured: Up to 21 days after the first dose

  9. Phase Ib: AUC0-inf

    Area Under the Curve（0-inf）of GNC-035 will be investigated.

    Measured: Up to 21 days after the first dose

  10. Phase Ib: AUC0-T

    Area Under the Curve（0-t）of GNC-035 will be investigated.

    Measured: Up to 21 days after the first dose

  11. Phase Ib: CL

    Rate of clearance of GNC-035 will be investigated.

    Measured: Up to 21 days after the first dose

  12. Phase Ib: T1/2

    Half-life (T1/2) of GNC-035 will be investigated.

    Measured: Up to 21 days after the first dose

  13. Phase Ib: Anti-drug antibody (ADA)

    Frequency of anti-GNC-035 antibody (ADA) will be investigated.

    Measured: Up to approximately 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jul 2023
  2. Study start16 Aug 2023
  3. Primary completionDec 2025 (estimated)
  4. Study completionDec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05944978
Sponsor's protocol ID
GNC-035-105
Status last verified
Sep 2025
First submitted
6 Jul 2023
Last updated
26 Sep 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing GNC-035 in people with Relapsed/Refractory Chronic Lymphocytic Leukemia, run by Sichuan Baili Pharmaceutical Co., Ltd. at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 26 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase Ib: Dose limiting toxicity (DLT) (time frame: Up to 21 days after the first dose). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05944978.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2025.

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