Phase Ib/II Clinical Study of GNC-035 Tetra-specific Antibody Injection in Relapsed or Refractory Chronic Lymphocytic Leukemia and Other Hematological Malignancies
Overview
- Phase
- Phase 1
- Intervention
- GNC-035
- Conditions
- Relapsed/Refractory Chronic Lymphocytic Leukemia
- Sponsor
- Sichuan Baili Pharmaceutical Co., Ltd.
- Enrollment
- 3
- Locations
- 1
- Primary Endpoint
- Phase Ib: Dose limiting toxicity (DLT)
- Status
- Active, not recruiting
- Last Updated
- 7 months ago
Overview
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
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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);
Arms & Interventions
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.
Intervention: GNC-035
Outcomes
Primary Outcomes
Phase Ib: Dose limiting toxicity (DLT)
Time Frame: Up to 21 days after the first dose
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.
Phase Ib: Maximum tolerated dose (MTD)
Time Frame: Up to 21 days after the first dose
MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle .
Phase Ib: Recommended Phase II Dose (RP2D)
Time Frame: Up to 21 days after the first dose
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.
Phase II: Objective Response Rate (ORR)
Time Frame: Up to approximately 24 months
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.
Phase Ib: Treatment-Emergent Adverse Event (TEAE)
Time Frame: Up to approximately 24 months
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.
Secondary Outcomes
- Phase Ib: Objective Response Rate (ORR)(Up to approximately 24 months)
- Progression-free survival (PFS)(Up to approximately 24 months)
- Duration of Response (DOR)(Up to approximately 24 months)
- Phase Ib: Anti-drug antibody (ADA)(Up to approximately 24 months)
- Phase Ib: Cmax(Up to 21 days after the first dose)
- Disease Control Rate (DCR)(Up to approximately 24 months)
- Phase Ib: Complete Response (CR)(Up to approximately 24 months)
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Phase Ib: AUC0-inf(Up to 21 days after the first dose)
- Phase Ib: Tmax(Up to 21 days after the first dose)
- Phase Ib: AUC0-T(Up to 21 days after the first dose)
- Phase Ib: CL(Up to 21 days after the first dose)
- Phase Ib: T1/2(Up to 21 days after the first dose)